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EA5163, A Randomized, Phase III Study of Firstline Immunotherapy Alone or in Combination With Chemotherapy in Induction/Maintenance or Postprogression in Advanced Nonsquamous Non-Small Cell Lung Cancer (NSCLC) With Immunobiomarker SIGNature-Driven Analysis (NSCLC)

A Study to Evaluate Firstline Pembrolizumab Alone or in Combination with Pemetrexed and Carboplatin in Induction/Maintenance or Postprogression in Treating Patients with Stage IV Non-squamous Non-small Cell Lung Cancer

Mina Hanna
All
18 years and over
Phase 3
This study is NOT accepting healthy volunteers
0000-100998-P01-ALCL
19-005867
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Inclusion Criteria:

  • Patients must have histologically or cytologically confirmed stage IV non-squamous non‐small cell lung cancer (NSCLC) (includes M1a, M1b stage disease, American Joint Committee on Cancer [AJCC] 8th edition). Patients with T4NX disease (stage IIIB and IIIC) with nodule in ipsilateral lung lobe are eligible if they are not candidates for combined chemotherapy and radiation/
  • Patients must have PD-L1 expression Tumor Proportion Score (TPS) ≥ 1% in tumor cells. If PD-L1 expression TPS is unevaluable or the testing could not be completed, the patients are not eligible. The assay must have been performed by a Clinical Laboratory Improvement Act (CLIA) (or equivalent) certified laboratory.
  • Patients must have measurable or non-measurable disease. The presence of malignant pleural fluid alone is sufficient to satisfy this eligibility criterion. Baseline imaging assessments and measurements used to evaluate all measurable or non-measurable sites of disease must be done within 4 weeks prior to study registration.
    • NOTE: If patient receives pemetrexed, follow institutional guidelines to drain fluids.
  • Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. 
  • Patients must NOT have received the following: 
    • Prior systemic chemotherapy or immunotherapy for advanced metastatic NSCLC. Patients treated with any prior checkpoint inhibitors for metastatic lung cancer are ineligible. Chemotherapy for non-metastatic disease (e.g., adjuvant therapy) or immunotherapy for locally advanced stage III disease is allowed if at least 6 months have elapsed between the last dose of the prior therapy and study registration. Local therapy, e.g. palliative radiation, is allowed as long as a period of 14 days has passed between completion of local therapy and study registration;
    • Methotrexate (MTX) given in low doses for non-malignant conditions with last dose at least 14 days prior to date of registration will be allowed. Other low dose chemotherapeutics for non-malignant conditions will be considered, but review by the study chair is required.
  • Patients with known EGFR mutations (except exon 20 insertion), BRAF mutations (V600) or ALK or ROS1 translocations that can be treated with oral tyrosine kinase inhibitors are excluded.
  • Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression. Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy.
  • Patients are eligible if off steroids for at least 14 days prior to protocol treatment.
  • Anticonvulsants are allowed.
  • Patients with prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
  • Patients must not have known pre-existing and clinically active interstitial lung disease, or a known history of (non infectious) pneumonitis that required steroids, or current pneumonitis.
  • Patients must not have significant gastrointestinal disorders with diarrhea as a major symptom (e.g,. Crohn's disease, malabsorption, etc.). 
  • Patients must not have history of auto-immune condition requiring ongoing or intermittent systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
  • Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
  • Patients must not have any other concomitant serious illness or organ system dysfunction that in the opinion of the investigator would either compromise patient safety or interfere with the evaluation of the safety of the study drug.
  • Patients must not receive any other investigational agents during the course of therapy.
  • Women must not be pregnant or breast-feeding due to potential harm to the fetus or infant from cytotoxic chemotherapy and the unknown risk of MK-3475 (pembrolizumab). Patients must also not expect to conceive or father children from the time of registration, while on study treatment, and until at least 120 days after the last dose of study treatment:
    • All females of childbearing potential must have a blood test or urine study within 72 hours prior to registration to rule out pregnancy;
    • A female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: has achieved menarche at some point; has not undergone a hysterectomy or bilateral oophorectomy; or has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).
  • Women of childbearing potential and sexually active males must use an accepted and effective method of contraception or abstain from sexual intercourse from time of registration, while on study treatment, and continue for 120 days after the last dose of study treatment.
  • Absolute neutrophil count (ANC) ≥ 1500/mm^3 (within 14 days of randomization).
  • Platelets ≥ 100,000/mm^3 (within 14 days of randomization).
  • Prothrombin time (PT)/international normalized ratio (INR) ≤ 1.5 Or if patient on therapeutic anticoagulation, PT/INR ≤ 3.0 (within 14 days of randomization).
  • Partial thromboplastin time (PTT) ≤ institutional upper limit of normal (ULN) OR, if patient is on therapeutic anticoagulation, PTT must be ≤ 1.5 x ULN (within 14 days of randomization).
  • Total bilirubin ≤ 1.5 mg/dL (obtained within 14 days of randomization).
  • Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) < 5 x upper limit of normal (ULN) (obtained within 14 days of randomization)
    •Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 5 x upper limit of normal (ULN) (obtained within 14 days of randomization).
  • Calculated creatinine clearance ≥ 45ml/min to be eligible to receive pemetrexed (obtained within 14 days prior to randomization). 
  • Serum creatinine ≤ 1.5 x institutional upper limit of normal (ULN) (obtained within 14 days prior to randomization).
  • Patients must not have a known history of active tuberculosis (TB).
  • Patients must not have a diagnosis of immunodeficiency or receive systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of protocol treatment.
  • Patients must not have received a live vaccine within 30 days prior to randomization. Seasonal flu vaccines that do not contain live virus are permitted.
  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
  • For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
Biologic/Vaccine, Drug, Administration of antineoplastic agent, Chemotherapy, Drug therapy, Immunotherapy for cancer
Cancer, Lung cancer, Non-small cell lung cancer
Biological therapy for cancer, Cancer treatment, Carboplatin, Chemotherapy, Medical Oncology, Non-small cell carcinoma of lung, TNM stage 4, Nonsquamous nonsmall cell neoplasm of lung, Pembrolizumab [USAN:INN], Pemetrexed, Respiratory system, carboplatin, pembrolizumab, pemetrexed
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Mayo Clinic Health System — Albert Lea, MN

EA5163, A Randomized, Phase III Study of Firstline Immunotherapy Alone or in Combination With Chemotherapy in Induction/Maintenance or Postprogression in Advanced Nonsquamous Non-Small Cell Lung Cancer (NSCLC) With Immunobiomarker SIGNature-Driven Analysis

A Study to Evaluate Firstline Pembrolizumab Alone or in Combination with Pemetrexed and Carboplatin in Induction/Maintenance or Postprogression in Treating Patients with Stage IV Non-squamous Non-small Cell Lung Cancer

Amrit Singh
All
18 years and over
Phase 3
This study is NOT accepting healthy volunteers
0000-100998-P01-MAIJ
19-005867
Show full eligibility criteria
Hide eligibility criteria

Inclusion Criteria:

  • Patients must have histologically or cytologically confirmed stage IV non-squamous non‐small cell lung cancer (NSCLC) (includes M1a, M1b stage disease, American Joint Committee on Cancer [AJCC] 8th edition). Patients with T4NX disease (stage IIIB and IIIC) with nodule in ipsilateral lung lobe are eligible if they are not candidates for combined chemotherapy and radiation/
  • Patients must have PD-L1 expression Tumor Proportion Score (TPS) ≥ 1% in tumor cells. If PD-L1 expression TPS is unevaluable or the testing could not be completed, the patients are not eligible. The assay must have been performed by a Clinical Laboratory Improvement Act (CLIA) (or equivalent) certified laboratory.
  • Patients must have measurable or non-measurable disease. The presence of malignant pleural fluid alone is sufficient to satisfy this eligibility criterion. Baseline imaging assessments and measurements used to evaluate all measurable or non-measurable sites of disease must be done within 4 weeks prior to study registration.
    • NOTE: If patient receives pemetrexed, follow institutional guidelines to drain fluids.
  • Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. 
  • Patients must NOT have received the following: 
    • Prior systemic chemotherapy or immunotherapy for advanced metastatic NSCLC. Patients treated with any prior checkpoint inhibitors for metastatic lung cancer are ineligible. Chemotherapy for non-metastatic disease (e.g., adjuvant therapy) or immunotherapy for locally advanced stage III disease is allowed if at least 6 months have elapsed between the last dose of the prior therapy and study registration. Local therapy, e.g. palliative radiation, is allowed as long as a period of 14 days has passed between completion of local therapy and study registration;
    • Methotrexate (MTX) given in low doses for non-malignant conditions with last dose at least 14 days prior to date of registration will be allowed. Other low dose chemotherapeutics for non-malignant conditions will be considered, but review by the study chair is required.
  • Patients with known EGFR mutations (except exon 20 insertion), BRAF mutations (V600) or ALK or ROS1 translocations that can be treated with oral tyrosine kinase inhibitors are excluded.
  • Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression. Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy.
  • Patients are eligible if off steroids for at least 14 days prior to protocol treatment.
  • Anticonvulsants are allowed.
  • Patients with prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
  • Patients must not have known pre-existing and clinically active interstitial lung disease, or a known history of (non infectious) pneumonitis that required steroids, or current pneumonitis.
  • Patients must not have significant gastrointestinal disorders with diarrhea as a major symptom (e.g,. Crohn's disease, malabsorption, etc.). 
  • Patients must not have history of auto-immune condition requiring ongoing or intermittent systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
  • Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
  • Patients must not have any other concomitant serious illness or organ system dysfunction that in the opinion of the investigator would either compromise patient safety or interfere with the evaluation of the safety of the study drug.
  • Patients must not receive any other investigational agents during the course of therapy.
  • Women must not be pregnant or breast-feeding due to potential harm to the fetus or infant from cytotoxic chemotherapy and the unknown risk of MK-3475 (pembrolizumab). Patients must also not expect to conceive or father children from the time of registration, while on study treatment, and until at least 120 days after the last dose of study treatment:
    • All females of childbearing potential must have a blood test or urine study within 72 hours prior to registration to rule out pregnancy;
    • A female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: has achieved menarche at some point; has not undergone a hysterectomy or bilateral oophorectomy; or has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).
  • Women of childbearing potential and sexually active males must use an accepted and effective method of contraception or abstain from sexual intercourse from time of registration, while on study treatment, and continue for 120 days after the last dose of study treatment.
  • Absolute neutrophil count (ANC) ≥ 1500/mm^3 (within 14 days of randomization).
  • Platelets ≥ 100,000/mm^3 (within 14 days of randomization).
  • Prothrombin time (PT)/international normalized ratio (INR) ≤ 1.5 Or if patient on therapeutic anticoagulation, PT/INR ≤ 3.0 (within 14 days of randomization).
  • Partial thromboplastin time (PTT) ≤ institutional upper limit of normal (ULN) OR, if patient is on therapeutic anticoagulation, PTT must be ≤ 1.5 x ULN (within 14 days of randomization).
  • Total bilirubin ≤ 1.5 mg/dL (obtained within 14 days of randomization).
  • Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) < 5 x upper limit of normal (ULN) (obtained within 14 days of randomization)
    •Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 5 x upper limit of normal (ULN) (obtained within 14 days of randomization).
  • Calculated creatinine clearance ≥ 45ml/min to be eligible to receive pemetrexed (obtained within 14 days prior to randomization). 
  • Serum creatinine ≤ 1.5 x institutional upper limit of normal (ULN) (obtained within 14 days prior to randomization).
  • Patients must not have a known history of active tuberculosis (TB).
  • Patients must not have a diagnosis of immunodeficiency or receive systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of protocol treatment.
  • Patients must not have received a live vaccine within 30 days prior to randomization. Seasonal flu vaccines that do not contain live virus are permitted.
  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
  • For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
Biologic/Vaccine, Drug, Administration of antineoplastic agent, Chemotherapy, Drug therapy, Immunotherapy for cancer
Cancer, Lung cancer, Non-small cell lung cancer
Biological therapy for cancer, Cancer treatment, Carboplatin, Chemotherapy, Medical Oncology, Non-small cell carcinoma of lung, TNM stage 4, Nonsquamous nonsmall cell neoplasm of lung, Pembrolizumab [USAN:INN], Pemetrexed, Respiratory system, carboplatin, pembrolizumab, pemetrexed
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Mayo Clinic Health System — Mankato, MN

MC1931 Pharmacodynamic Study of Estrogen Suppression Threshold-Directed Therapy (ESTDT) of Anastrozole as Adjuvant Therapy for Early Stage Breast Cancer

Anastrozole and Letrozole After Surgery for the Treatment of Stage I-III Breast Cancer

Tufia Haddad
Female
18 years and over
Phase 2
This study is NOT accepting healthy volunteers
0000-101000-P01-RST
19-006637
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Inclusion Criteria
•Registration:

  • Women of age ≥ 18 years.
  • Histological confirmation of invasive breast carcinoma.
  • Stage I-III breast cancer
  • Estrogen receptor (ER) positive disease according to ASCO/CAP guidelines as ER≥1% positive nuclear staining.
  • Completion of all planned cancer treatments prior to registration:
    • surgical resection of breast and nodal surgery;
    • NOTE: Reconstructive surgery does not have to be completed
    • adjuvant radiation therapy, if needed; and
    • neoadjuvant and/or adjuvant chemotherapy, if needed.
  • Post-menopausal defined as
  • Age ³60 and amenorrhea >12 consecutive months OR
  • Previous bilateral oophorectomy OR
  • Age <60 and amenorrhea >12 consecutive months and documented follicle stimulating hormone (FSH) level within post-menopausal range according to institutional standard
  • NOTE: Patients who did not meet these criteria at time of diagnosis and received pre-operative (neoadjuvant) or post-operative (adjuvant) chemotherapy will not be allowed to participate.
  • ECOG Performance Status (PS) 0, 1, or 2 .
  • The following laboratory values obtained ≤14 days prior to registration:
    • Hemoglobin ≥ 8.0 g/dL;
    • Absolute neutrophil count (ANC) ≥ 1500/mm^3;
    • Platelet count ≥ 70,000/mm^3;
    • Total bilirubin ≤ 1.5 x ULN;
    • Alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤ 3 x ULN.
  • Ability to swallow oral medication.
  • Provide written informed consent.
  • Willingness to provide mandatory blood specimens for correlative research.
  • Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study).

Exclusion Criteria
•Registration:

 

  • Pre-menopausal women receiving ovarian function suppression (goserelin, leuprolide, etc.).
  • Stage IV (metastatic) breast cancer.
  • HER2 positive breast cancer as defined by:
    • HER2 IHC ≥ 3+;
    • HER2/CEP17 ≥ 2.0;
    • HER2/CEP17 < 2.0 and average HER2 copy number of ≥ 6.0. signals/cell
  • Prior endocrine therapy for this breast cancer.
  • Exceptions:
    • Pre-operative aromatase therapy (anastrozole, letrozole, or exemestane)  and last treatment was ≥ 4 weeks prior to registration; OR
    • Pre-operative tamoxifen therapy and last treatment was ≥ 12 weeks prior to registration.
  • Currently receiving any of the following cancer-directed therapies:
    • Radiation therapy;
    • Systemic therapy such as chemotherapy (standard or investigational);
    • Bisphosphonate therapy started < 4 weeks prior to registration.
  • NOTE: If patient is currently on bisphosphonate therapy she must be on stable dose for ≥ 4 weeks prior to registration.
  • Patients not currently taking bisphosphonates will be allowed to start bisphosphonate therapy after completion of anastrozole (1mg and 10 mg daily (if given)). Information regarding bisphosphonate therapy will be collected.
  • Current use of systemic or topical exogenous estrogen or progesterone (menopausal hormone replacement therapy [HRT]).
  • Prior ovarian function suppression (leuprolide, goserelin, etc).
  • Inability to provide informed consent.
  • History of contralateral DCIS or invasive breast cancer.
  • NOTE: Exception allowed if:
    • Patient did not receive adjuvant endocrine therapy; OR
    • Patient received adjuvant endocrine therapy but has been off treatment for at least 6 months prior to registration.
  • Concurrent active malignancy or history of malignancy ≤ 3 years prior to registration.
  • NOTE: Exceptions allowed for successfully treated cervical carcinoma in situ, lobular carcinoma in situ of the breast, papillary thyroid cancer, or non-melanoma skin cancer.
  • Prior prevention therapy with an aromatase inhibitor or a SERM.
  • Exception: Therapy with a SERM (tamoxifen or raloxifene) is allowed if patient has been off treatment for ≥ 6 months prior to registration.
Drug, Administration of antineoplastic agent, Drug therapy, Estrogen hormone therapy
Breast cancer, Cancer
Cancer treatment, Malignant tumor of breast, Medical Oncology, anastrozole, Anastrozole, Breast cancer surgery, Letrozole, letrozole, Hormone therapy for breast cancer
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Mayo Clinic — Rochester, MN

PrOspective Non-interventional Study in Patients With Locally Advanced or Metastatic TRK Fusion Cancer Treated With Larotrectinib (ON-TRK)

Study to Learn More About the Safety and Effectiveness of the Drug VITRAKVI During Routine Use in Patients With TRK Fusion Cancer Which is Locally Advanced or Spread From the Place Where it Started to Other Places in the Body

Scott Okuno
All
Not specified
This study is NOT accepting healthy volunteers
0000-101002-P01-RST
19-004701
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Inclusion Criteria:

  • Adult and pediatric (from birth to 18 year old) patients.
  • Patients with locally advanced or metastatic solid tumor harboring an NTRK gene fusion. NTRK (NTRK1, NTRK2, and NTRK3) gene fusions will be identified locally. Acceptable methods of detection of NTRK gene fusion include NGS, fluorescence in situ hybridization (FISH), reverse-transcription polymerase chain reaction (rt-PCR) or any other genomic testing able to detect NTRK gene fusion. If a pan-TRK IHC method is used, this result needs to be accompanied with the results using one of the other methods noted above. 
  • Life expectancy of at least 3 months based on clinical judgement.
  • Decision to treat with larotrectinib made by the treating physician prior to study enrollment.
  • Signed informed consent form.
  • For patients under legal age, signed assent by the patient (where applicable) and parental/legal guardian signed informed consent is required.


Exclusion Criteria:

  • Any contraindications as listed in the local approved product information.
  • Pregnancy.
  • Participation in an investigational program with interventions outside of routine clinical practice.
  • Prior treatment with larotrectinib or other kinase inhibitor with TRK inhibition.
  • Patients with NTRK gene amplification or NTRK point mutation.
Cancer
Alteration of genetic material, Cancer treatment, Larotrectinib [USAN:INN], Medical Oncology, Secondary malignant neoplastic disease, Solid neoplasm with neurotrophic receptor tyrosine kinase gene fusion, Targeted drug therapy, larotrectinib
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Mayo Clinic — Rochester, MN

S1806, Phase III Randomized Trial of Concurrent Chemoradiotherapy With or Without Atezolizumab in Localized Muscle Invasive Bladder Cancer (Study SWOG/NRG 1806)

A Study to Evaluate Chemoradiotherapy with or without Atezolizumab in Treating Patients With Localized Muscle Invasive Bladder Cancer

Brian Costello
All
18 years and over
Phase 3
This study is NOT accepting healthy volunteers
0000-101018-P01-RST
19-005141
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Inclusion Criteria:
 

STEP 1 REGISTRATION

  • If this will be the first patient from a registering site to receive a given RT modality (3DCRT vs. IMRT), the site must first submit pre-RT planning documents within 3 days of Step 1 registration and receive approval from Imaging and Radiation Oncology Core (IROC) before randomizing the patient to Step 2. If this will not be the first patient to receive a specific RT modality, the patient should be immediately randomized to Step 2 on the same day. 

STEP 2 RANDOMIZATION

  • If patient required review of pre-RT planning, randomization must occur within 14 days of initial registration. 
  • Patients must have histologically proven, T2-T4a N0M0 urothelial carcinoma of the bladder within 70 days prior to randomization. Patients with mixed urothelial carcinoma will be eligible for the trial, but the presence of small cell carcinoma will make a patient ineligible. Patients with lymph nodes ≥ 1.0 cm in shortest cross-sectional diameter on imaging (computed tomography [CT]/magnetic resonance imaging [MRI]) must have a biopsy of the enlarged lymph node showing no tumor involvement within 70 days prior to randomization. These patients may be suitable for neoadjuvant chemotherapy and radical cystectomy and are eligible for this trial if they seek out a bladder sparing treatment strategy, however patients who have received prior systemic chemotherapy for bladder cancer are not eligible for the trial. 
  • Patients must undergo a transurethral resection of bladder tumor (TURBT) within 70 days prior to randomization. In a situation where a patient is referred from outside to the enrolling institution, patient must have a repeat cystoscopy by the urologist who will be following the patient on the clinical trial to assess the adequacy of the prior TURBT. Patient may then undergo repeat TURBT if deemed necessary as standard of care by the treating urologist. Patients may have either completely or partially resected tumors as long as the treating urologist attempted maximal resection. Patient must not have T4b disease. 
  • Patients must undergo radiological staging within 70 days prior to randomization. Imaging of chest, abdomen, and pelvis must be performed using CT or MRI. Patients must not have evidence of T4bN1-3 disease. Eligibility is based on the local radiology report. 
  • Patients with hydronephrosis are eligible if they have unilateral hydronephrosis and kidney function meets criteria specified. 
  • Patients must not have had urothelial carcinoma or histological variant at any site outside of the urinary bladder within the previous 24 months except Ta/T1/carcinoma in situ (CIS) of the upper urinary tract including renal pelvis and ureter if the patient had undergone complete nephroureterectomy. 
  • Patients must not have diffuse CIS based on cystoscopy and biopsy. 
  • Patient must be planning to receive one of the protocol specified chemotherapy regimens.
  • All adverse events associated with any prior surgery and intravesical therapy must have resolved to Common Terminology Criteria for Adverse Events (CTCAE) grade ≤ 2 prior to randomization. 
  • Patient must not have received any systemic chemotherapy for their bladder cancer. 
  • Patient must not have had prior pelvic radiation. 
  • Patients must not have received prior treatment for muscle invasive bladder cancer including neoadjuvant chemotherapy for the current tumor. 
  • Patients must not have received any systemic therapy (including, but not limited to, interferon alfa-2b, high dose IL-2, pegylated interferon [PEG-IFN], anti-PD-1, anti-PD-L1), for non-muscle invasive bladder cancer. Prior intravesical BCG, interferon, and intravesical chemotherapy are allowed. 
  • Patients must not have received any of the following prohibited therapies within 28 days prior to randomization or be planning to receive any of the following prohibited therapies during protocol treatment: 
    • Anti-cancer systemic chemotherapy or biological therapy not specified in the protocol
    • Immunotherapy not specified in this protocol;
    • Systemic or intravesical use of any non-study anti-cancer agent (investigational or non-investigational);
    • Investigational agents other than atezolizumab;
    • Live vaccines: Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, shingles, yellow fever, rabies, bacillus Calmette-Guerin (BCG), and typhoid (oral) vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines, and are not allowed. Prior administration of intravesical BCG is allowed;
    • Glucocorticoids for any purpose other than to modulate symptoms from an event of suspected immunologic etiology. The use of physiologic doses of corticosteroids (defined as 10 mg prednisone) are acceptable, however site investigators should consult with the study chair for any dose higher than 10 mg prednisone. Dexamethasone 4 mg iv with chemotherapy to prevent nausea is allowed;
    • RANKL infusion: Concurrent denosumab (which binds the cytokine RANKL) for any known indication is prohibited due to interaction with study medication. 
  • Patients must not have a major surgical procedure within 28 days prior to randomization. If patient had any surgical procedure then they should have recovered to full presurgical performance status and surgical adverse events should have resolved to grade ≤ 2. TURBT is not considered a major surgical procedure. 
  • Patients must not have received treatment with systemic immunosuppressive medications (including, but not limited to, prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [anti-TNF] agents) within 14 days prior to randomization. Exceptions: 
    • Patients may have received acute, low dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea);
    • The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed. Physiological doses equivalent of 10 mg prednisone daily are allowed. Short term steroids given as antiemetic therapy; e.g., 4 mg dexamethasone or equivalent once a week, is allowed. 
  • Patients must not have received a live, attenuated vaccine within 4 weeks prior to randomization or anticipate that such a live, attenuated vaccine will be required while on protocol treatment and up to 5 months after the last dose of protocol treatment. 
    • Inactivated influenza vaccination should be given during influenza season only (approximately October to March). Patients must not receive live, attenuated influenza vaccine within 4 weeks prior to randomization or while on protocol treatment and up to 5 months after the last dose of protocol treatment. 
  • Patients must not have undergone prior allogeneic bone marrow transplantation or prior solid organ transplantation. 
  • Patient may or may not be radical cystectomy candidates.
  • Absolute neutrophil count (ANC) ≥ 1,500/microliter (mcL) (within 28 days prior to randomization). 
  • Platelets ≥ 100,000/mcL (within 28 days prior to randomization).
  • Hemoglobin ≥ 9 g/dL (within 28 days prior to randomization).
  • Total bilirubin ≤ 1.5 x institutional upper limit of normal (IULN) (except patients with Gilbert's syndrome, who must have a total bilirubin < 3.0 mg/dL) (within 28 days prior to randomization). 
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 2.5 x IULN (within 28 days prior to randomization). 
  • Patients must not have clinically significant liver disease that precludes patient from treatment regimens prescribed on the study (including, but not limited to, active viral, alcoholic or other autoimmune hepatitis, cirrhosis or inherited liver disease). 
  • Patients must have adequate renal function as evidenced by calculated creatinine clearance ≥ 25 mL/min. The creatinine used to calculate the clearance result must have been obtained within 28 days prior to randomization. 
  • Patients must have Zubrod performance status ≤ 2. 
  • Patients must have a baseline electrocardiography (ECG) performed within 30 days prior to randomization. 
  • Patient must not have history of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis. 
  • Patients must not have an active infection requiring oral or IV antibiotics within 14 days prior to randomization. Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are not eligible. If patient develops urinary tract infection after TURBT they must have recovered from the infection prior to registration.
  • Patients must not have active autoimmune disease that has required systemic treatment in past two years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Autoimmune diseases include, but are not limited to, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Bell's palsy, Guillain-Barré syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, Graves' disease treated with methimazole or glomerulonephritis. 
  • Patient must not have a history of active tuberculosis. 
  • If patient has a known history of hepatitis B virus (HBV) or hepatitis C virus (HCV), they must meet the following criteria within 28 days prior to randomization. 
    • Patients with past or resolved hepatitis B infection (defined as having a negative hepatitis B surface antigen [HBsAg] test and a positive anti-HBc [antibody to hepatitis B core antigen] antibody test) are eligible;
    • Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV ribonucleic acid (RNA). 
  • Patients who are known to be positive for human immunodeficiency virus (HIV) are eligible only if they have all of the following: 
    • A stable regimen of highly active anti-retroviral therapy (HAART);
    • No requirement for concurrent antibiotics or antifungal agents for the prevention of opportunistic infections;
    • A CD4 count above 250 cells/mcL and an undetectable HIV viral load on standard PCR-based tests within 28 days prior to randomization.
  • No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for two years. Patients with localized prostate cancer who are being followed by an active surveillance program are also eligible. 
  • Female patients of childbearing potential must have a serum pregnancy test prior to randomization. Patients must not be pregnant or nursing due to the potential teratogenic side effects of the protocol treatment. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of protocol treatment, and for 5 months (150 days) after the last dose of all study drugs. A woman is considered to be of "reproductive potential" if she has had a menses at any time in the preceding 12 consecutive months. 
  • Patients must not be known to be allergic to Chinese hamster egg or ovary cell products and must not have any known major allergic reactions to any study drug. 
  • Patients must be offered the opportunity to participate in specimen banking for future studies. 
  • Patients who can complete Patient-Reported Outcome instruments in English or Spanish must agree to complete the EORTC QLQ-C30, the EORTC QLQ-BLM30, the EPIC-26 (bowel domain only), and the EQ-5D-5L per protocol schedule of assessment. 
  • As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system.
Drug, Other, Radiation, Administration of antineoplastic agent, Chemotherapy, Combined chemotherapy and radiation therapy, Drug therapy, Immunotherapy for cancer, Radiation oncology AND/OR radiotherapy
Bladder cancer, Cancer
Atezolizumab, Biological therapy for cancer, Cancer treatment, Carcinoma of urinary bladder, invasive, Chemotherapy, IMRT, Malignant tumor of urinary bladder, Medical Oncology, Radiation therapy, Transitional cell carcinoma of bladder, Urinary system, atezolizumab
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Mayo Clinic — Rochester, MN

MEK-NF-201, A Phase 2b Trial of the MEK 1/2 Inhibitor (MEKi) PD-0325901 in Adult and Pediatric Patients With Neurofibromatosis Type 1 (NF1)-Associated Inoperable Plexiform Neurofibromas (PNs) That Are Causing Significant Morbidity (RENEU)

A Study to Assess the MEK Inhibitor Mirdametinib (PD-0325901) in Patients with Neurofibromatosis Type 1 Associated Plexiform Neurofibromas

Dusica Babovic-Vuksanovic
All
2 years and over
Phase 2
This study is NOT accepting healthy volunteers
0000-101019-P01-RST
19-003466
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Inclusion Criteria:

  • Participant has documented NF1 mutation or a diagnosis of neurofibromatosis type 1 (NF1) using National Institute of Health (NIH) Consensus Conference criteria inclusive of the presence of a plexiform neurofibroma (PN). 
  • Participant has a PN that is causing significant morbidity. 
  • Participant has a PN that cannot be completely surgically removed.
  • Participant has a target tumor that is amenable to volumetric MRI analysis. 
  • Participant is willing to undergo a tumor biopsy pre- and end of treatment if ≥ 18 years of age. 
  • Participant has adequate organ and bone marrow function.
  • Participant can swallow capsules whole if the capsule dosage form is being utilized. This criterion does not apply if participant is utilizing the dispersible tablet dosage form of study treatment;


Exclusion Criteria:
 

  • Participant has abnormal liver function or history of liver disease.
  • Participant has lymphoma, leukemia or any malignancy within the past 5 years (except for resected basal/squamous skin carcinomas without metastases within 3 years). 
  • Participant has breast cancer within 10 years.
  • Participant has active optic glioma or other low-grade glioma requiring treatment. 
  • Participant has abnormal QT interval corrected or other heart disease within 6 months.
  • Participant has a history of retinal pathology, risk factors for retinal vein occlusion or has a history of glaucoma. 
  • Participant has known malabsorption syndrome or gastrointestinal conditions that would impair absorption of PD-0325901. 
  • Participant has received NF1 PN-targeted therapy within 45 days. 
  • Participant has received radiation therapy within 6 months or has received radiation to the orbit at any time. 
  • Participant is unable to undergo or tolerate MRI.
  • Participant has active bacterial, fungal or viral infection.
  • Participant has experienced other severe acute or chronic medical or psychiatric conditions within 1 year.
Behavioral, Drug, Drug therapy
Neurofibroma, Neurofibromatosis
MRI, Mirdametinib [USAN], Nervous system, Neurofibromatosis type 1, Plexiform neurofibroma, Tumor surgically unresectable
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Mayo Clinic — Rochester, MN

A Phase III, Randomized, Double-Blind, Placebo-Controlled, Multi Center Study of Durvalumab Monotherapy or in Combination With Bevacizumab as Adjuvant Therapy in Patients With Hepatocellular Carcinoma Who Are at High Risk of Recurrence After Curative Hepatic Resection or Ablation (EMERALD-2)

A Study to Assess the Effectiveness and Safety of Durvalumab Alone or Combined with Bevacizumab in High Risk of Recurrence HCC Patients After Curative Treatment

Sean Cleary
All
18 years to 150 years old
Phase 3
This study is NOT accepting healthy volunteers
0000-101020-P01-RST
19-005862
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Inclusion Criteria:
 

  • Male and female.
  • Provision of signed and dated written informed consent form (ICF) and any locally required authorization (e.g., Health Insurance Portability and Accountability Act in the US, EU Data Privacy Directive in the EU) obtained from the patient (or legal representative / impartial witness where mandated & allowed by local regulations) prior to any mandatory study-specific procedures, sampling, and analyses, including screening evaluations.
  • Age ≥ 18 years at the time of screening. For patients aged < 20 years and enrolled in Japan, a written informed consent should be obtained from the patient and his or her legally acceptable representative. Patients aged < 21 years must not be enrolled in Egypt or Singapore.
  • Histologically or cytologically (or radiologically for patients undergoing curative ablation) confirmed HCC, newly diagnosed, and successfully completed curative therapy (resection or ablation). (a) Hepatic resection and have the following pathologic and/or radiologic findings from surgery: (i) Any size with microvascular invasion (clear pathologic assessment on microvascular invasion: Yes or No) and/or satellite tumor (ii) 3 or less tumors, with at least one > 5 cm (iii) 4 or more tumors, ≤ 5 cm each (b) Ablation (radiofrequency or microwave, cryoablation, or PEI per institutional standard. Embolisation (e.g., TACE/TAE) is acceptable so long as it is part of the local planned ablative process) where all curative procedures are completed within a 12 week window, and have the following radiologic findings prior to ablation: (i) Solitary tumor, 3 to 5 cm (ii) 2 to 4 tumors, ≤ 5 cm each (iii) Exclude patients with 5 or more tumors.
  • Patients must be randomized within 12 weeks of completion of curative hepatic resection, or final curative ablation procedure.
  • Imaging to confirm disease-free status within 28 days prior to randomization.
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 1 at enrollment.
  • Child-Pugh score of 5 or 6. 8 Patients with active HBV infection (as characterized by positive hepatitis B virus surface antigen [HBsAg] and/or anti-hepatitis B core antibodies (HBcAbs) with detectable HBV deoxyribonucleic acid (DNA) [≥10 IU/mL or above the limit of detection per local laboratory]) must receive antiviral therapy at least after enrollment (sign of ICF) per institutional practice. Patients must remain on antiviral therapy for the study duration and for 6 months after the last dose of study treatment. Patients must show evidence of HBV stabilization or signs of viral response (e.g., reduction HBV DNA levels) prior to randomization. Patients who test positive for anti-HBcAb with undetectable HBV DNA (< 10 IU/mL or under the limit of detection per local laboratory) do not require antiviral therapy. These patients will be tested at every cycle to monitor HBV DNA levels and initiate antiviral therapy if HBV DNA is detected (≥ 10 IU/mL or above the limit of detection per local laboratory). Patients with detectable HBV DNA during the study must initiate and remain on antiviral therapy for the study duration and for 6 months after the last dose of study treatment.
  • Patients with active HCV infection (as characterized by the presence of detectable HCV ribonucleic acid (RNA)) must be managed per local institutional practice for the study duration.
  • Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. A definition of post-menopausal.
  • Adequate organ and marrow function, as defined below. Criteria “a,” “b,” “c,” and “f” cannot be met with transfusions, infusions, or growth factor support administered within 14 days of starting the first dose:
    • Hemoglobin ≥ 9 g/dL;
    •  Absolute neutrophil count ≥ 1000/µL;
    • Platelet count ≥ 65000/µL;
    • Total bilirubin (TBL) ≤ 2.0 × upper limit of normal (ULN);
    • Aspartate aminotransferase (AST) and ALT ≤ 5 × ULN;
    •  Albumin ≥ 2.8 g/dL;
    • International normalized ratio ≤ 1.6 (for patients receiving Warfarin, please consult with the study physician);
    • Urine protein 2+ or less;
    • Tested blood urea nitrogen or creatinine ≤ 1.5 × ULN or calculated creatinine clearance (CL) ≥ 51 mL/min as determined by the Cockcroft-Gault formula (using actual WT) or 24-hour urine creatinine CL;
    • Males: Creatinine CL (mL/min)=WT (kg) × (140
      •Age) 72 × serum creatinine (mg/dL); Females:  Creatinine CL (mL/min) = WT (kg) × (140
      •Age) × 0.85 72 × serum creatinine (mg/dL).


Exclusion Criteria:
 

  • History of deep vein thrombosis, pulmonary embolism, or any other significant thromboembolism (venous port or catheter thrombosis or superficial venous thrombosis are not considered “significant”) during the 3 months prior to randomization.
  • History of significant bleeding disorders, vasculitis, or a significant bleeding episode from the GI tract within 3 months prior to study randomization.
  • History of GI perforation and/or fistulae within 6 months prior to randomization.
  • Any history of nephrotic or nephritic syndrome.
  • Evidence of symptomatic congestive heart failure (New York Heart Association II to IV) or symptomatic or poorly controlled cardiac arrhythmia.
  • History of arterial thrombotic event, including myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack, within 6 months prior to randomization.
  • Uncontrolled arterial hypertension defined by a systolic pressure ≥ 150 mm Hg or diastolic pressure ≥ 90 mm Hg despite standard medical management.
  • Serious or non-healing wound, peptic ulcer, or bone fracture within 28 days prior to randomization.
  • Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC.
  • Evidence, by Investigator assessment, of varices at risk of bleeding on upper endoscopy or contrast-enhanced cross-sectional imaging undertaken at the screening visit, or within 6 months (24 weeks) of randomization.
  • Evidence of distant metastasis (except regional lymph node metastases related to the disease under study, per Appendix F), co-existing malignant disease or macrovascular invasion on baseline imaging.
  • History of hepatic encephalopathy within 12 months prior to randomization or requirement for medications to prevent or control encephalopathy (no lactulose, rifaximin, etc, if used for purposes of hepatic encephalopathy).
  • Evidence of portal vein thrombosis, visible on baseline/eligibility imaging, and patients with Vp1, Vp2, Vp3 and Vp4 (benign portal vein thrombosis is allowed, where not related to tumor thrombus, and anti-thrombotics may be used as needed).
  • Clinically meaningful ascites, defined as ascites requiring non-pharmacologic intervention (e.g., paracentesis) to maintain symptomatic control, within 6 months prior to the first dose of study treatment. (a) Patients with ascites who have required pharmacologic intervention (e.g., diuretics) and who have been on stable doses of diuretics for ascites for ≥ 2 months before randomization are eligible.
  • Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, colitis or Crohn's disease], diverticulitis [except for diverticulosis], systemic lupus erythematosus, sarcoidosis syndrome, or Wegener syndrome [e.g., granulomatosis with polyangiitis, Graves’ disease, rheumatoid arthritis, hypophysitis, and uveitis]). The following are exceptions to this criterion:
    • Patients with vitiligo or alopecia;
    • Patients with hypothyroidism (e.g., following Hashimoto syndrome), stable on hormone replacement;
    • Any chronic skin condition that does not require systemic therapy;
    • Patients without active disease in the last 5 years may be included but only after consultation with the Study Physician;
    • Patients with celiac disease controlled by diet alone.
    • Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, uncontrolled cardiac arrhythmia, active interstitial lung disease (ILD), serious chronic GI conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirements, substantially increase the risk of incurring AEs or compromise the ability of the patient to give written informed consent.
    • History of another primary malignancy except for the following:
      • Prostate cancer of pathologic stage less than or equal to T2cN0M0 determined from a prior prostatectomy without biochemical recurrence and who, in the opinion of the Investigator, are not deemed to require active intervention, or patients with incidental histologic findings of prostate cancer that has not been treated prior to the study and who do not require specific therapy for prostate cancer beyond the surgery described in the Clinical Study Protocol and also are considered to be at low risk for recurrence per the Investigator;
      • Malignancy treated with curative intent and with no known active disease ≥ 5 years before the first dose of study treatment and of low potential risk for recurrence;
      • Adequately treated non-melanoma skin cancer or lentigo malignant without evidence of disease;
      • Adequately treated carcinoma in situ without evidence of disease;
      • Patients with another primary malignancy that is not active or expected to be clinically relevant in the next 5 years may be considered further to discussion with the Study Physician.
  • Active infection, including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis testing in line with local practice) or human immunodeficiency virus (HIV; positive for HIV 1/2 antibodies).
  • Active co-infection with both HBV and hepatitis D virus.
  • Known allergy or hypersensitivity to any of the study treatments or any of the study treatment excipients.
  • History of aneurysm (Patients with a capped aneurysm may be included but only after consultation with the Study Physician).
  • Major surgery (as defined by the Investigator) within 28 days prior to randomization, or central venous access device placement within 7 days prior to randomization (biopsy from any type of surgery within 28 days is not an exclusion criteria, nor are procedures to treat varices).
  • Receipt of routine treatment for chronic condition with nonsteroidal anti-inflammatory agents (e.g., indomethacin, ibuprofen, naproxen, or similar agents) or other anti-platelet agents (e.g., clopidogrel, ticlopidine, dipyridamole, or anagrelide). Require minimum washout period of 5 days prior to randomization. Low dose aspirin (≤ 325 mg/day) is permitted. Prohibited concomitant medications with exceptions.
  • Receipt of prior systemic anticancer therapy for HCC.
  • History of allogeneic organ transplantation or those who are on a waiting list for liver transplantation.
  • Receipt of live attenuated vaccine within 30 days prior to the first dose of study treatment.
    • Note: Patients, if enrolled, should not receive live vaccine while receiving study treatment and up to 90 days after the last dose of study treatment.
  • Current or prior use of immunosuppressive medication within 14 days before the first dose of study treatment. The following are exceptions to this criterion:
    • Intranasal, inhalational, topical steroids, or local steroid injections (e.g., intra-articular injection);
    • Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent;
    • Steroids as pre-medication for hypersensitivity reactions (e.g., CT-scan premedication).
  • Receipt of treatment with herbal medications labelled for the treatment of HCC (e.g., Huaier) within 14 days prior to first dose of study treatment.
  • Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ highly effective birth control from screening to 6 months after the last dose of study treatment. Not engaging in sexual activity, per the patient’s preferred and usual lifestyle, for the total duration of the treatment and 6 months after the last dose of study treatment is an acceptable practice.
  • Judgment by the Investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions, and requirements.
  • Involvement in the planning and/or conduct of the study for both AstraZeneca staff and/or staff at the study site.

Eligibility last updated 10/7/21. Questions regarding updates should be directed to the study team contact.

 

 

Biologic/Vaccine, Drug, Other, Administration of antineoplastic agent, Chemotherapy, Destruction of lesion of liver, Destructive procedure, Drug therapy, Immunotherapy for cancer, Removal of liver lesion
Cancer, Hepatocellular carcinoma, Liver cancer, Liver tumor
Ablation, At risk of malignancy, Bevacizumab, Biological therapy for cancer, Cancer treatment, Chemotherapy, Digestive system, Durvalumab [USAN:INN], Liver cell carcinoma, Liver tumor ablation, Medical Oncology, bevacizumab, durvalumab
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Mayo Clinic — Rochester, MN

A Phase III, Randomized, Double-blind, Placebo-controlled, Multicenter Study of Transarterial Chemoembolization (TACE) in Combination With Either Durvalumab Monotherapy or Durvalumab Plus Bevacizumab Therapy in Patients With Locoregional Hepatocellular Carcinoma (EMERALD-1) (EMERALD-1)

Study to Evaluate Chemoembolization Combined with Durvalumab and Bevacizumab Therapy in Patients With Locoregional Hepatocellular Carcinoma

Nguyen Tran
All
18 years to 110 years old
Phase 3
This study is NOT accepting healthy volunteers
0000-101021-P01-RST
19-006050
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Inclusion Criteria:

  • Male and/or female.
  • Age ≥ 18 years at the time of screening. For patients aged < 20 years and enrolled in Japan, a written informed consent should be obtained from the patient and his or her legally acceptable representative.
  • Confirmed HCC (by imaging or histopathologically from biopsy specimen).
  • No evidence of extrahepatic disease on any available imaging.
  • Disease not amenable to curative surgery or transplantation or curative ablation.
  • Disease must be amenable to TACE and anticipated to require no more than 4 TACE treatments to treat sites of disease within a ≤ 16-week period (Permitted modalities are DEB-TACE or cTACE (using an emulsion of Lipiodol® and a permitted chemotherapeutic agent as per institutional practice, followed by embolizing agents).
  • Child-Pugh score class A to B7.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at enrollment 10. Patients with HBV infection, which is characterized by positive hepatitis B surface antigen (HBsAg) and/or hepatitis B core antibodies (anti-HBcAb) with detectable HBV DNA (≥ 10 IU/ml or above the limit of detection per local lab standard), must be treated with antiviral therapy, as per institutional practice. HBV antiviral therapy must be initiated prior to randomization and patients must remain on antiviral therapy for the study duration and for 6 months after the last dose of study medication. Patients must show evidence HBV stabilization or signs of viral response (e.g., reduction HBV DNA levels) prior to starting IP. Patients who test positive for anti-hepatitis B core (HBc) with undetectable HBV DNA (< 10 IU/ml or under the limit of detection per local lab standard) do not require antiviral therapy prior to randomization. These subjects will be tested at every cycle to monitor HBV DNA levels and initiate antiviral therapy if HBV DNA is detected (≥ 10 IU/ml or above the limit of detection per local lab standard). HBV DNA detectable subjects must initiate and remain on antiviral therapy for the study duration and for 6 months after the last dose of study medication.
  • Patients with HCV infection must have management of this disease per local institutional practice throughout the study. HCV diagnosis is characterized by the presence of detectable HCV ribonucleic acid (RNA) or anti-HCV antibody upon enrollment.
  • At least 1 measurable intrahepatic lesion suitable for repeat assessments according to the following mRECIST criteria:
    • Liver lesions that show typical features of HCC on IV contrast-enhanced CT or MRI scans; i.e., hypervascularity in the arterial phase with washout in the portal or the late venous phase;
    • Viable, non-necrotic portion (arterial phase IV contrast-enhancing) that can be accurately measured at baseline as ≥ 10 mm in the longest diameter.
  • Adequate organ and marrow function as defined below. Criteria “a,” “b,” “c,” and “f” may not be met with transfusions, infusions, or growth factor support administered within 14 days of starting the first dose:
    • Hemoglobin ≥ 9.0 g/dL;
    • Absolute neutrophil count ≥1000/µL;
    • Platelet count ≥ 75000/µL;
    • Total bilirubin ≤ 2.0 × the upper limit of normal (ULN);
    • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 × ULN;
    • Albumin ≥2.8 g/dL;
    • International normalized ratio ≤1.6;
    • 2+ proteinuria or less urine dipstick reading;
    • Calculated creatinine clearance (CL) ≥ 30 mL/min as determined by Cockcroft-Gault (using actual body weight) or 24-hour urine creatinine CL.
    • Males: Creatinine CL = Weight (kg) × (140
      •Age) (mL/min) 72 × serum creatinine (mg/dL);
    • Females: Creatinine CL = Weight (kg) × (140
      •Age) × 0.85 (mL/min) 72 × serum creatinine (mg/dL). 
  • Must have a life expectancy of at least 12 weeks.
  • Upper Endoscopy to evaluate varices and risk of bleeding is required within 6 months of randomization.
  • Body weight >30 kg


Exclusion Criteria:

  • Any history of nephrotic or nephritic syndrome.
  • Clinically significant (e.g., active) cardiovascular disease, including:
    • Unstable angina within ≤ 6 months of randomization;
    • New York Heart Association Grade ≥ 2 congestive heart failure;
    • Poorly controlled cardiac arrhythmia despite medication (patient with rate controlled atrial fibrillation are eligible), or any clinically significant abnormal finding on resting ECG.
  • Peripheral vascular disease Grade ≥ 3 (e.g., symptomatic and interfering with activities of daily living requiring repair or revision).
  • Significant traumatic injury during 4 weeks prior to randomization.
  • Known hereditary predisposition to bleeding or thrombosis; any prior or current evidence of bleeding diathesis.
  • Systemic anticoagulation allowed, excluding Vitamin K antagonists.
  • History of arterial thrombotic event, including myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack, within 6 months prior to randomization 
  • Non-healing wound, active ulcer, or bone fracture. Patients with granulating incisions healing by secondary intention with no evidence of facial dehiscence or infection are eligible but require wound examinations every 3 weeks.
  • History of abdominal fistula or GI perforation, nonhealed gastric ulcer that is refractory to treatment, or active GI bleeding within 6 months prior to enrollment.
  • Patients who have had any kind of surgery in the past 28 days (biopsy from any type of surgery within 28 days is not an exclusion criteria. Nor are procedures to treat varices.) 
  • Uncontrolled hypertension defined by a systolic pressure > 150 mmHg or diastolic pressure > 90 mmHg, with or without antihypertensive medication. Patients with initial blood pressure (BP) elevations are eligible if initiation or adjustment of antihypertensive medication lowers pressure to meet entry criteria.
  • Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC.
  • History of hepatic encephalopathy within past 12 months or requirement for medications to prevent or control encephalopathy (no lactulose, rifaximin, etc, if used for purposes of hepatic encephalopathy).
  • Clinically meaningful ascites, defined as ascites requiring non-pharmacologic intervention (e.g., paracentesis) to maintain symptomatic control, within 6 months prior to the first scheduled dose:
    • Patients with ascites that has required pharmacologic intervention (e.g., diuretics) and who have been on stable doses of diuretics for ascites for ≥ 2 months are eligible;
    • Major portal vein thrombosis visible on baseline/eligibility imaging, patients with Vp3 and Vp4 are excluded.
  • Patients with infiltrative-type HCC.
  • History of allogeneic organ transplantation.
  • Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn’s disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [eg, granulomatosis with polyangiitis, Graves’ disease, rheumatoid arthritis, hypophysitis, and uveitis]). The following are exceptions to this criterion:
    • Patients with vitiligo or alopecia;
    • Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement;
    • Any chronic skin condition that does not require systemic therapy;
    • Patients without active disease in the last 5 years may be included but only after consultation with the Study Physician;
    • Patients with celiac disease controlled by diet alone.
    • Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection (except for noted HBV or HCV as detailed above), symptomatic congestive heart failure, poorly controlled diabetes mellitus, uncontrolled hypertension, unstable angina pectoris, uncontrolled cardiac arrhythmia, active ILD, serious chronic GI conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent.
  • History of another primary malignancy except for:
    • Malignancy treated with curative intent and with no known active disease ≥ 5 years before the first dose of IP and of low potential risk for recurrence;
    • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease;
    • Adequately treated carcinoma in situ without evidence of disease.
  • History of leptomeningeal carcinomatosis.
  • History of active primary immunodeficiency.
  • Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis testing in line with local practice) or human immunodeficiency virus (positive HIV 1/2 antibodies).
  • Patients co-infected with HBV and hepatitis D virus (HDV). (HBV infection is indicated by the presence of HBsAg and/or anti-HBcAb with detectable HBV DNA ≥ 10 IU/mL or above the limit of detection per local lab standard ; HDV positive infection is indicated by the presence of anti-HDV antibodies.)
  • Any unresolved toxicity National Cancer Institute (NCI) CTCAE v 5.0 Grade ≥ 2 from previous anticancer therapy, with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria.
  • Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
  • History of allogeneic bone marrow transplant and active chronic graft versus host disease.
  • Receipt of anti-PD-1, anti-PD-L1, or anti-CTLA-4 prior to the first dose of IP.
  • Receipt of prior TACE, prior bland embolization, or prior radioembolization. Use of TACE or TAE as part of a curative therapy (e.g., in conjuntion with ablation or surgery) can be acceptable if it is used in the lesions where curative therapy was attempted. However, TACE or TAE cannot have been used as sole modalities in prior curative therapy.
  • Receipt of prior systemic anticancer therapies for HCC.
  • Receipt of live attenuated vaccine within 30 days prior to the first dose of IP.
    • Note: Patients, if enrolled, should not receive live vaccine while receiving IP and up to 90 days after the last dose of IP.
  • Current or prior use of immunosuppressive medication within 14 days before the first dose of IP. The following are exceptions to this criterion:
    • Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection);
    • Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent;
    • Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
  • Concurrent enrollment in another clinical study, unless it is an observational (noninterventional) clinical study or during the follow-up period of an interventional study.
  • Prior randomization or treatment in a previous durvalumab clinical study regardless of treatment group assignment.
  • Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ highly effective birth control from screening to 6 months after the last dose of IP. Not engaging in sexual activity, as per the patient’s preferred and usual lifestyle, for the total duration of the treatment and 6 months after the last dose of study treatment is an acceptable practice.
  • Judgment by the Investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions, and requirements.
  • Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
Drug, Procedure/Surgery, Other, Administration of antineoplastic agent, Chemotherapy, Drug therapy, Immunotherapy for cancer, Transarterial chemoembolization of hepatic artery
Cancer, Hepatocellular carcinoma, Liver cancer
Bevacizumab, Biological therapy for cancer, Cancer treatment, Chemoembolization, Chemoembolization for liver cancer, Chemotherapy, Digestive system, Durvalumab [USAN:INN], Liver cell carcinoma, Medical Oncology, bevacizumab, durvalumab
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Mayo Clinic — Rochester, MN

Limited Stage Small Cell Lung Cancer (LS-SCLC): A Phase II/III Randomized Study of Chemoradiation Versus Chemoradiation Plus Atezolizumab

Chemoradiation With or Without Atezolizumab in Treating Patients With Limited Stage Small Cell Lung Cancer

Konstantinos Leventakos
All
18 years and over
Phase 2/3
This study is NOT accepting healthy volunteers
0000-101023-P01-RST
19-005349
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Inclusion Criteria:

  • Pathologically (histologically or cytologically) proven diagnosis of limited stage small cell lung cancer (Stage Tx, T1-T4, N0-3, M0, American Joint Committee on Cancer [AJCC] staging, 8th edition [Ed.]), within 60 days prior to registration.
  • Patients must have received one pre-registration cycle of platinum/etoposide chemotherapy prior to study entry, with study registration required within 21 days from day 1 of the pre-registration cycle of chemotherapy and protocol treatment designed to begin 21 days after. If patient has not recovered from pre-registration cycle chemotherapy toxicities, then an additional 14 days is permitted.
  • Patients must have had measurable disease (per Response Evaluation Criteria in Solid Tumors [RECIST], version 1.1) prior to the required cycle of platinum/etoposide chemotherapy.
  • Minimal staging requirements include:
    • History/physical examination within 30 days prior to registration;
    • Positron emission tomography (PET)/computed tomography (CT) scan for staging within 45 days prior to registration;
    • CT chest/abdomen with IV contrast (unless contraindicated based on kidney function) within 45 days prior to registration
      •this can be obtained as part of PET/CT if CT imaging is of diagnostic quality.
      • Note: If contrast allergy exists, premedication per institutional guidelines should be performed prior to obtaining CT with contrast. The only exception to this is a documented life-threatening allergy.
    • Magnetic resonance imaging (MRI) scan of the brain with contrast (preferred) or CT scan of the brain with contrast (allowable if there is a contraindication with MRI with contrast) within 30 days prior to registration. 
    • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 within 30 days prior to registration.
    • Absolute neutrophil count (ANC) ≥ 1, 500/cells/mm^3 (pre-registration cycle)
    • Platelet count ≥ 100,000 cells/mm^3 (pre-registration cycle).
    • Hemoglobin ≥ 9 g/dL (pre-registration cycle).
    • Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (pre-registration cycle).
    • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) ≤ 2.0 x ULN (pre-registration cycle).
    • Glomerular filtration rate (GFR) ≥ 50 mL/min/1.73 m^2 (within 30 days prior to registration).
    • Patients presenting with a pleural effusion will be eligible if thoracentesis is cytologically negative and non-bloody or if pleural fluid is too small a volume to effectively sample by thoracentesis and does not show increased metabolic activity on CT/PET imaging.
    • Negative serum pregnancy test within 14 days of registration for pre-menopausal women of childbearing potential.
    • The patient or a legally authorized representative must provide study-specific informed consent prior to study entry.


Exclusion Criteria:
 

  • Definitive clinical or radiologic evidence of metastatic disease.
  • Definitive surgical resection of small cell lung cancer.
  • Prior invasive malignancy (except non-melanomatous skin cancer, localized prostate cancer, or any early stage cancer treated with curative intent resection) unless disease free for a minimum of 2 years (carcinoma in situ of the breast, oral cavity, or cervix are all permissible).
  • More than 1 cycle of prior platinum-based chemotherapy for SCLC prior to enrollment; note that prior chemotherapy for a different cancer is allowable.
  • Any prior atezolizumab or other immunotherapy agent.
  • Prior radiotherapy to the lungs or mediastinum that would result in clinically significant overlap of radiation therapy fields; prior tangent fields for breast cancer with minimal overlap with target volumes are allowed per approval of study principal investigators (PIs).
  • Patients with cytologically positive pleural or pericardial fluid are not eligible. 
  • An active, known or suspected autoimmune disease. Patients are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger.
  • Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis).
  • History of allogeneic organ transplant
  • History of primary immunodeficiency.
  • Severe, active co-morbidity defined as follows: 
    • Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis, cirrhosis, fatty liver, and inherited liver disease;
    • Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications;
    • Active tuberculosis;
    • Active hepatitis B (chronic or acute) or hepatitis C infection.
      • Note that if hepatitis status is unknown, hepatitis B/C testing is required:
        • Patients with past or resolved hepatitis B infection (defined as having a negative hepatitis B surface antigen [HBsAg]) test, a positive anti-HBc (antibody to hepatitis B core antigen), and a negative viral deoxyribonucleic acid (DNA) test (only obtained if HBsAg is found positive) are eligible.  Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV ribonucleic acid (RNA). (The HCV RNA test must be performed for patients who have a positive HCV antibody test).
    • Known immunosuppressive disease, for example history of bone marrow transplant or chronic lymphocytic leukemia (CLL):
      • CD4 count < 200 cells/microliter.
        • Note that patients who are human immunodeficiency virus (HIV) positive are eligible, provided they are under treatment with highly active antiretroviral therapy (HAART) and have a CD4 count ≥ 200 cells/microliter within 30 days prior to registration. Note also that HIV testing is not required for eligibility for this protocol.
    • Chronic obstructive pulmonary disease (COPD) requiring chronic oral steroid therapy of > 10 mg prednisone daily or equivalent at the time of registration. Inhaled corticosteroids are not exclusionary. 
    • Unstable angina and/or congestive heart failure requiring hospitalization within the last 3 months. 
    • Transmural myocardial infarction within the last 3 months.
    • Clinically significant interstitial lung disease. 
  • A condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
  • Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception for the duration of study treatment and for 150 days after the last dose of study drug (Arm 2); this exclusion is necessary because the treatment involved in this study may be significantly teratogenic.
Drug, Other, Radiation, Administration of antineoplastic agent, Combined chemotherapy and radiation therapy, Drug therapy, Immunotherapy for cancer
Cancer, Lung cancer, Small cell lung cancer
1,2-Diaminocyclohexaneplatinum II citrate, Atezolizumab, Biological therapy for cancer, Cancer treatment, Carboplatin, Chemotherapy, Etoposide, Medical Oncology, Radiation therapy, Respiratory system, Small cell carcinoma of lung, atezolizumab, carboplatin, cisplatin, etoposide
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Mayo Clinic — Rochester, MN

Limited Stage Small Cell Lung Cancer (LS-SCLC): A Phase II/III Randomized Study of Chemoradiation Versus Chemoradiation Plus Atezolizumab

Chemoradiation With or Without Atezolizumab in Treating Patients With Limited Stage Small Cell Lung Cancer

Mina Hanna
All
18 years and over
Phase 2/3
This study is NOT accepting healthy volunteers
0000-101023-P01-ALCL
19-005349
Show full eligibility criteria
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Inclusion Criteria:

  • Pathologically (histologically or cytologically) proven diagnosis of limited stage small cell lung cancer (Stage Tx, T1-T4, N0-3, M0, American Joint Committee on Cancer [AJCC] staging, 8th edition [Ed.]), within 60 days prior to registration.
  • Patients must have received one pre-registration cycle of platinum/etoposide chemotherapy prior to study entry, with study registration required within 21 days from day 1 of the pre-registration cycle of chemotherapy and protocol treatment designed to begin 21 days after. If patient has not recovered from pre-registration cycle chemotherapy toxicities, then an additional 14 days is permitted.
  • Patients must have had measurable disease (per Response Evaluation Criteria in Solid Tumors [RECIST], version 1.1) prior to the required cycle of platinum/etoposide chemotherapy.
  • Minimal staging requirements include:
    • History/physical examination within 30 days prior to registration;
    • Positron emission tomography (PET)/computed tomography (CT) scan for staging within 45 days prior to registration;
    • CT chest/abdomen with IV contrast (unless contraindicated based on kidney function) within 45 days prior to registration
      •this can be obtained as part of PET/CT if CT imaging is of diagnostic quality.
      • Note: If contrast allergy exists, premedication per institutional guidelines should be performed prior to obtaining CT with contrast. The only exception to this is a documented life-threatening allergy.
    • Magnetic resonance imaging (MRI) scan of the brain with contrast (preferred) or CT scan of the brain with contrast (allowable if there is a contraindication with MRI with contrast) within 30 days prior to registration. 
    • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 within 30 days prior to registration.
    • Absolute neutrophil count (ANC) ≥ 1, 500/cells/mm^3 (pre-registration cycle)
    • Platelet count ≥ 100,000 cells/mm^3 (pre-registration cycle).
    • Hemoglobin ≥ 9 g/dL (pre-registration cycle).
    • Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (pre-registration cycle).
    • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) ≤ 2.0 x ULN (pre-registration cycle).
    • Glomerular filtration rate (GFR) ≥ 50 mL/min/1.73 m^2 (within 30 days prior to registration).
    • Patients presenting with a pleural effusion will be eligible if thoracentesis is cytologically negative and non-bloody or if pleural fluid is too small a volume to effectively sample by thoracentesis and does not show increased metabolic activity on CT/PET imaging.
    • Negative serum pregnancy test within 14 days of registration for pre-menopausal women of childbearing potential.
    • The patient or a legally authorized representative must provide study-specific informed consent prior to study entry.


Exclusion Criteria:
 

  • Definitive clinical or radiologic evidence of metastatic disease.
  • Definitive surgical resection of small cell lung cancer.
  • Prior invasive malignancy (except non-melanomatous skin cancer, localized prostate cancer, or any early stage cancer treated with curative intent resection) unless disease free for a minimum of 2 years (carcinoma in situ of the breast, oral cavity, or cervix are all permissible).
  • More than 1 cycle of prior platinum-based chemotherapy for SCLC prior to enrollment; note that prior chemotherapy for a different cancer is allowable.
  • Any prior atezolizumab or other immunotherapy agent.
  • Prior radiotherapy to the lungs or mediastinum that would result in clinically significant overlap of radiation therapy fields; prior tangent fields for breast cancer with minimal overlap with target volumes are allowed per approval of study principal investigators (PIs).
  • Patients with cytologically positive pleural or pericardial fluid are not eligible. 
  • An active, known or suspected autoimmune disease. Patients are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger.
  • Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis).
  • History of allogeneic organ transplant
  • History of primary immunodeficiency.
  • Severe, active co-morbidity defined as follows: 
    • Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis, cirrhosis, fatty liver, and inherited liver disease;
    • Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications;
    • Active tuberculosis;
    • Active hepatitis B (chronic or acute) or hepatitis C infection.
      • Note that if hepatitis status is unknown, hepatitis B/C testing is required:
        • Patients with past or resolved hepatitis B infection (defined as having a negative hepatitis B surface antigen [HBsAg]) test, a positive anti-HBc (antibody to hepatitis B core antigen), and a negative viral deoxyribonucleic acid (DNA) test (only obtained if HBsAg is found positive) are eligible.  Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV ribonucleic acid (RNA). (The HCV RNA test must be performed for patients who have a positive HCV antibody test).
    • Known immunosuppressive disease, for example history of bone marrow transplant or chronic lymphocytic leukemia (CLL):
      • CD4 count < 200 cells/microliter.
        • Note that patients who are human immunodeficiency virus (HIV) positive are eligible, provided they are under treatment with highly active antiretroviral therapy (HAART) and have a CD4 count ≥ 200 cells/microliter within 30 days prior to registration. Note also that HIV testing is not required for eligibility for this protocol.
    • Chronic obstructive pulmonary disease (COPD) requiring chronic oral steroid therapy of > 10 mg prednisone daily or equivalent at the time of registration. Inhaled corticosteroids are not exclusionary. 
    • Unstable angina and/or congestive heart failure requiring hospitalization within the last 3 months. 
    • Transmural myocardial infarction within the last 3 months.
    • Clinically significant interstitial lung disease. 
  • A condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
  • Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception for the duration of study treatment and for 150 days after the last dose of study drug (Arm 2); this exclusion is necessary because the treatment involved in this study may be significantly teratogenic.
Drug, Other, Radiation, Administration of antineoplastic agent, Combined chemotherapy and radiation therapy, Drug therapy, Immunotherapy for cancer
Cancer, Lung cancer, Small cell lung cancer
1,2-Diaminocyclohexaneplatinum II citrate, Atezolizumab, Biological therapy for cancer, Cancer treatment, Carboplatin, Chemotherapy, Etoposide, Medical Oncology, Radiation therapy, Respiratory system, Small cell carcinoma of lung, atezolizumab, carboplatin, cisplatin, etoposide
I'm interested
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Location Contacts
Mayo Clinic Health System — Albert Lea, MN

Limited Stage Small Cell Lung Cancer (LS-SCLC): A Phase II/III Randomized Study of Chemoradiation Versus Chemoradiation Plus Atezolizumab

Chemoradiation With or Without Atezolizumab in Treating Patients With Limited Stage Small Cell Lung Cancer

Amrit Singh
All
18 years and over
Phase 2/3
This study is NOT accepting healthy volunteers
0000-101023-P01-MAIJ
19-005349
Show full eligibility criteria
Hide eligibility criteria

Inclusion Criteria:

  • Pathologically (histologically or cytologically) proven diagnosis of limited stage small cell lung cancer (Stage Tx, T1-T4, N0-3, M0, American Joint Committee on Cancer [AJCC] staging, 8th edition [Ed.]), within 60 days prior to registration.
  • Patients must have received one pre-registration cycle of platinum/etoposide chemotherapy prior to study entry, with study registration required within 21 days from day 1 of the pre-registration cycle of chemotherapy and protocol treatment designed to begin 21 days after. If patient has not recovered from pre-registration cycle chemotherapy toxicities, then an additional 14 days is permitted.
  • Patients must have had measurable disease (per Response Evaluation Criteria in Solid Tumors [RECIST], version 1.1) prior to the required cycle of platinum/etoposide chemotherapy.
  • Minimal staging requirements include:
    • History/physical examination within 30 days prior to registration;
    • Positron emission tomography (PET)/computed tomography (CT) scan for staging within 45 days prior to registration;
    • CT chest/abdomen with IV contrast (unless contraindicated based on kidney function) within 45 days prior to registration
      •this can be obtained as part of PET/CT if CT imaging is of diagnostic quality.
      • Note: If contrast allergy exists, premedication per institutional guidelines should be performed prior to obtaining CT with contrast. The only exception to this is a documented life-threatening allergy.
    • Magnetic resonance imaging (MRI) scan of the brain with contrast (preferred) or CT scan of the brain with contrast (allowable if there is a contraindication with MRI with contrast) within 30 days prior to registration. 
    • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 within 30 days prior to registration.
    • Absolute neutrophil count (ANC) ≥ 1, 500/cells/mm^3 (pre-registration cycle)
    • Platelet count ≥ 100,000 cells/mm^3 (pre-registration cycle).
    • Hemoglobin ≥ 9 g/dL (pre-registration cycle).
    • Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (pre-registration cycle).
    • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) ≤ 2.0 x ULN (pre-registration cycle).
    • Glomerular filtration rate (GFR) ≥ 50 mL/min/1.73 m^2 (within 30 days prior to registration).
    • Patients presenting with a pleural effusion will be eligible if thoracentesis is cytologically negative and non-bloody or if pleural fluid is too small a volume to effectively sample by thoracentesis and does not show increased metabolic activity on CT/PET imaging.
    • Negative serum pregnancy test within 14 days of registration for pre-menopausal women of childbearing potential.
    • The patient or a legally authorized representative must provide study-specific informed consent prior to study entry.


Exclusion Criteria:
 

  • Definitive clinical or radiologic evidence of metastatic disease.
  • Definitive surgical resection of small cell lung cancer.
  • Prior invasive malignancy (except non-melanomatous skin cancer, localized prostate cancer, or any early stage cancer treated with curative intent resection) unless disease free for a minimum of 2 years (carcinoma in situ of the breast, oral cavity, or cervix are all permissible).
  • More than 1 cycle of prior platinum-based chemotherapy for SCLC prior to enrollment; note that prior chemotherapy for a different cancer is allowable.
  • Any prior atezolizumab or other immunotherapy agent.
  • Prior radiotherapy to the lungs or mediastinum that would result in clinically significant overlap of radiation therapy fields; prior tangent fields for breast cancer with minimal overlap with target volumes are allowed per approval of study principal investigators (PIs).
  • Patients with cytologically positive pleural or pericardial fluid are not eligible. 
  • An active, known or suspected autoimmune disease. Patients are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger.
  • Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis).
  • History of allogeneic organ transplant
  • History of primary immunodeficiency.
  • Severe, active co-morbidity defined as follows: 
    • Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis, cirrhosis, fatty liver, and inherited liver disease;
    • Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications;
    • Active tuberculosis;
    • Active hepatitis B (chronic or acute) or hepatitis C infection.
      • Note that if hepatitis status is unknown, hepatitis B/C testing is required:
        • Patients with past or resolved hepatitis B infection (defined as having a negative hepatitis B surface antigen [HBsAg]) test, a positive anti-HBc (antibody to hepatitis B core antigen), and a negative viral deoxyribonucleic acid (DNA) test (only obtained if HBsAg is found positive) are eligible.  Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV ribonucleic acid (RNA). (The HCV RNA test must be performed for patients who have a positive HCV antibody test).
    • Known immunosuppressive disease, for example history of bone marrow transplant or chronic lymphocytic leukemia (CLL):
      • CD4 count < 200 cells/microliter.
        • Note that patients who are human immunodeficiency virus (HIV) positive are eligible, provided they are under treatment with highly active antiretroviral therapy (HAART) and have a CD4 count ≥ 200 cells/microliter within 30 days prior to registration. Note also that HIV testing is not required for eligibility for this protocol.
    • Chronic obstructive pulmonary disease (COPD) requiring chronic oral steroid therapy of > 10 mg prednisone daily or equivalent at the time of registration. Inhaled corticosteroids are not exclusionary. 
    • Unstable angina and/or congestive heart failure requiring hospitalization within the last 3 months. 
    • Transmural myocardial infarction within the last 3 months.
    • Clinically significant interstitial lung disease. 
  • A condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
  • Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception for the duration of study treatment and for 150 days after the last dose of study drug (Arm 2); this exclusion is necessary because the treatment involved in this study may be significantly teratogenic.
Drug, Other, Radiation, Administration of antineoplastic agent, Combined chemotherapy and radiation therapy, Drug therapy, Immunotherapy for cancer
Cancer, Lung cancer, Small cell lung cancer
1,2-Diaminocyclohexaneplatinum II citrate, Atezolizumab, Biological therapy for cancer, Cancer treatment, Carboplatin, Chemotherapy, Etoposide, Medical Oncology, Radiation therapy, Respiratory system, Small cell carcinoma of lung, atezolizumab, carboplatin, cisplatin, etoposide
I'm interested
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Mayo Clinic Health System — Mankato, MN

(ECTx) TG4050.01; A phase I trial evaluating a mutanome-directed immunotherapy in patients with high grade serous carcinoma (HGSC) of the ovary, fallopian tube or peritoneum who experience an asymptomatic relapse

A Study to Evaluate TG4050 in Ovarian Carcinoma

Matthew Block
Female
18 years and over
Phase 1
This study is NOT accepting healthy volunteers
0000-101028-P01-RST
19-005397
Show full eligibility criteria
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Inclusion Criteria:
 

Screening Period

  • Signed written informed consent in accordance to ICH-GCP and national/local regulation before any protocol-related procedures that are not part of normal patient care.
  • Female patients ≥ 18 years of age.
  • Histologically confirmed high grade, stage IIIC or stage IV (FIGO staging) serous ovarian, fallopian or primary peritoneal carcinoma with abnormal CA-125 at diagnosis.
  • Patients who have undergone primary debulking surgery or interval debulking surgery and completed a total of at least 5 cycles of taxane-platinum combination.
    • Note: patients may have received concurrent or maintenance bevacizumab or a PARP inhibitor.
  • Patients must have achieved a complete response to therapy, as demonstrated by no residual disease on most recent CT scan and normal CA-125 not increasing by both the following: > 25% from nadir AND ≥ 10 UI/mL from nadir.
  • Patient who remains disease free at least 6 months from last prior dose of cytotoxic chemotherapy (maintenance therapy with bevacizumab or a PARP inhibitor is allowed).
  • Available tumor tissue, banked from previous abdominal debulking surgery and/or from a core needle biopsy performed at diagnosis if the patient received neoadjuvant chemotherapy, and peripheral blood samples for exome and transcriptome sequencing.

Treatment Period

  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at treatment period initiation.
  • Patients who have developed an asymptomatic relapse as defined by:
    • Cohort A: CA-125 ≥ 2 times ULN on 2 occasions at least 1 week apart (GCIG criteria) or low volume radiological disease and CA-125 > ULN. Low volume radiological disease is defined as radiologically visible disease excluding intra-hepatic or splenic metastases, ascites or pleural effusion thought to require drainage;
    • Cohort B: patient asymptomatic with measurable disease, excluding intra-hepatic or splenic metastases, ascites or pleural effusion thought to require drainage, whatever serum CA-125 level and for whom further treatment is not planned within 2 months.
    • Longest diameter on CT-scan must not exceed 2 cm for non-nodal lesions and 2.5 cm in short axis for nodal lesions.
  • Adequate hematological, hepatic and renal functions:
    • Hemoglobin ≥ 9.0 g/dL;
    • Neutrophils count ≥ 1.5 x10^9 /L;
    • Lymphocytes count ≥ 0.9 x10^9 /L;
    • Platelets count ≥ 100 x10^9 /L;
    • Total bilirubin ≤ 1.5 x ULN (except for patients with Gilbert’s syndrome);
    • Aspartate aminotransferase (AST) ≤ 2.5 x ULN;
    • Calculated creatinine clearance ≤ 45 mL/min using the Cockroft & Gault formula or ≥ 45 mL/min/1.73m² using other methods.
  • Patients who received standard maintenance therapy will stop before initiation of TG4050 administration. A free-interval of at least 30 days will be respected before first dosing of TG4050 except for PARP inhibitor (at least 14 days).


Exclusion Criteria:
 

Screening Period

  • Patient having received any cancer immunotherapy including cancer vaccines, any antibody/drug targeting T cell co-regulatory proteins such as anti-PD1, anti-PDL1 or anti-CTLA-4.
  • Patients with other active malignancy ≤ 3 years prior to registration except non-melanoma skin cancer, stage 0 in situ carcinoma and recent early stage papillary thyroid cancer. If there is an history of prior malignancy, patient must not be receiving other specific treatment for their cancer.
  • Patient post-organ transplantation, including allogeneic stem cell or bone marrow transplantation. History of blood transfusion within 3 weeks prior to study entry visit.
  • Known history of positive testing for Human Immunodeficiency Virus (HIV) or known AIDS (Acquired Immune Deficiency Syndrome).
  • Any known allergy or reaction to eggs or attributed to compounds of similar chemical or biological composition to therapeutic vaccines/immunotherapeutic products.
  • Positive serology for Hepatis C Virus (HCV) or positive serum Hepatitis B surface antigen (HBsAg) within 3 months prior to or at study entry (tests required).

Treatment Period

  • Measurable disease associated with the appearance of symptoms justifying initiation of further treatment.
  • Major surgery within 4 weeks prior to treatment start.
  • Treatment with another investigational agent within 30 days prior to TG4050 treatment initiation.
  • Patients under chronic treatment with systemic corticosteroids or other immunosuppressive drugs for a period of at least 4 weeks and whose treatment was not stopped 2 weeks prior to TG4050 treatment initiation planned date, with the exception of patients with adrenal insufficiency who may continue corticosteroids at physiological replacement dose, equivalent to ≤ 10 mg prednisone daily. Steroids with no or minimal systemic effect (topical, inhalation) are allowed.
  • Vaccination for the prevention of infectious diseases with a live vaccine during the four-week period prior to TG4050 treatment initiation planned date. Furthermore, patients should not receive any live vaccine during the period of study treatment administration.
  • Patient with any underlying medical condition, that in the opinion of the investigator, could make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety or toxicity of the study treatment.
  • Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia or psychiatric illness/social circumstances that could limit compliance with study requirements.
  • History of myocardial infarction ≤ 6 months.

Eligibility last updated 4/20/22. Questions regarding updates should be directed to the study team contact.

Drug, Administration of antineoplastic agent, Drug therapy, Immunotherapy for cancer
Cancer, Fallopian tube cancer, Ovarian cancer, Peritoneal cancer
Biological therapy for cancer, Cancer treatment, Extraovarian primary peritoneal carcinoma, Genetic mutation, Malignant tumor of fallopian tube, Malignant tumor of ovary, Medical Oncology, Primary adenocarcinoma of fallopian tube, Primary high grade serous adenocarcinoma of ovary, Reproductive system
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Mayo Clinic — Rochester, MN

A Phase 1 Study of TJ011133 Administered Alone or in Combination With Pembrolizumab or Rituximab in Subjects With Relapsed/Refractory Advanced Solid Tumors and Lymphoma

Study of TJ011133 in Participants With Relapsed/ Refractory Advanced Solid Tumors and Lymphoma

Mojun Zhu
All
18 years and over
Phase 1
This study is NOT accepting healthy volunteers
0000-101036-P01-RST
19-005251
Show full eligibility criteria
Hide eligibility criteria

Inclusion Criteria:
 

Part 1 Dose Escalation:

  • Histological or cytological diagnosis of solid tumor or Hodgkin’s Lymphoma who have relapsed or progressed and who are ineligible for all therapies with demonstrated clinical benefit.
    • Note: there is no limit to the number of prior treatment regimens; or
  • Relapsed/refractory CD20 positive, B-cell NHL who have progressed following at least 2 prior systemic therapies. For aggressive histologies, frontline treatment must have included an alkylating agent; or
  • Relapsed/refractory classical Hodgkin’s Lymphoma who have progressed following at least 2 prior systemic therapies and have progressed on checkpoint inhibitors (for Part 1B only);
  • In Part 1A (45 mg/kg dose cohort only), Part 1B or Part 1C, archival tumor tissue and fresh post-treatment tumor biopsy obtained that allows preparation of the number of slides required in the separate study-specific specimen preparation instructions. Samples will be collected, processed and stored according to a separate laboratory manual.

Part 2 Dose Expansion for Combination Therapy with Rituximab:

  • Relapsed/refractory DLBCL including histologically confirmed de novo (NOS) or transformed DLBCL (including transformation from follicular lymphoma of any grade, gastric MALT lymphoma and non-gastric MALT lymphoma) expressing CD20 by IHC (immunohistochemistry) or flow cytometry, primary mediastinal large B‐cell lymphoma, or T‐cell rich large B cell lymphoma, which are relapsed after at least 2 prior lines of systemic therapy including at least one rituximab-containing regimen or refractory disease to rituximab without better available choices.
  • Confirmed marginal zone or follicular lymphoma (Grade 1-3a) expressing CD20+ by IHC or flow cytometry, relapsed after at least 2 prior line of systemic therapy including at least one rituximab-chemotherapy combination regimen or refractory to rituximab-containing regimen without better available choices; for indolent NHL histology, progression following prior treatment with an alkylating agent is allowed but not required.
    • NOTE: Refractory disease is defined as progression within 6 months of last dose of therapy. Relapsed disease is defined as disease recurrence or PD following a response after more than 6 months after last dose. Patients who received CAR-T therapy are allowed but cannot have progressive disease within 3 months of CAR-T therapy.
    • At least one measurable lesion as defined by Lugano criteria (version 2014).
    • Available fresh metastatic biopsy sample prior to study entry and one mandatory on-treatment tumor biopsy in US clinical sites, unless there is difficulty obtaining the sample (e.g., hard to reach tumors or biopsies requiring surgical intervention). Waiver of biopsy samples must be discussed with the medical monitor. Tumor biopsy samples collected should allow for sample preparation as detailed in the separate study-specific specimen preparation instructions. Mandatory archival pre-treatment or optional ontreatment FFPE tumor tissue that allow for sample preparation as detailed in the separate study-specific specimen preparation instructions will be collected from subjects enrolled at sites in China in the NHL cohort of Part 2.

Part 2 Dose Expansion for Combination Therapy with Pembrolizumab:

  • Locally advanced or metastatic NSCLC that expresses PD-L1 (Tumor Proportion Score (TPS) ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum containing chemotherapy and checkpoint therapy.
  • Patients with NSCLC must have progressed on treatment with one prior PD1/L1 inhibitor administered either as monotherapy or in combination with other checkpoint inhibitors or other therapies.
  • Patients who have had more than 1 prior PD-(L)1 inhibitor may be considered after discussion with the Medical Monitor. PD-1/L1 inhibitor treatment progression is defined by meeting all of the following criteria:
    • has received at least 2 doses of the PD-1/L1 inhibitor (must be an approved PD-1/L1 inhibitor);
    • has been on a continuous regimen of the PD-1/L1 inhibitor for at least 4 months without disease progression;
    • has demonstrated radiographic disease progression after PD-1/L1.
  • Epithelial ovarian cancer, fallopian tube, or primary peritoneal cancer with any high-grade serous component and immune-oncology (IO) treatment naive subjects with metastases progressed on or after platinum-containing therapy and are not eligible for further platinum-containing treatment. Patients must meet the following criteria:
    • platinum-refractory, platinum-resistant disease defined by progression of disease on a platinum-containing regimen or recurrence of disease within 180 days of receiving the last dose of platinum-based treatment;
    • must not have progressed during the first 3 months of first line platinum-based therapy or must not have progressed within 3 months after completing first line platinum-based therapy;
    • must not have evidence of bowel obstruction requiring hospitalization and decompression within the past 30 days;
    • must not have ascites that requires therapeutic paracentesis in the last 30 days;
    • must not have tumors with low malignant potential (ie. borderline tumors) or mucinous tumors.
    • Prior lines of therapy to include:
      • Patients must have had 1 to 3 prior lines of therapy including at least one bevacizumab-containing regimen or ineligible for all other available therapies; Or
      • Patients must be in the 4th or 5th line of treatment, irrespective of bevacizumab or who are ineligible for all therapies with demonstrated clinical benefit; Or
      • Patients with known BRCA-positive associated cancer or mutation, prior therapy must include PARP inhibitors (unless contraindicated)
    • At least one measurable lesion as defined by RECIST 1.1 solid tumors.
    • Available fresh metastatic biopsy sample prior to study entry and one mandatory on-treatment tumor biopsy, unless there is difficulty obtaining the sample (e.g., hard to reach tumors or biopsies requiring surgical intervention). Waiver of biopsy samples must be discussed with the medical monitor. Tumor biopsy samples collected should allow for sample preparation as detailed in the separate study-specific specimen preparation instructions.

All Subjects:

  • Males or females, of any race, age ≥ 18 years;
  • Be willing and able to provide written informed consent for the trial.
  • Eastern Cooperative Oncology Group Performance Status 0 or 1.
  • Subjects able to follow the requirements of the study protocol and complete the trial.
  • Women of childbearing potential must:
    • Agree to use at least 2 effective contraceptive methods (1 highly effective method in combination with a barrier method; oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner), one of which must be barrier, from signing the ICF, throughout the study, and for up to 8 weeks following the last dose of TJ011133;
    • If using treatment with rituximab, women of childbearing potential should continue to use effective contraceptive methods for 12 months following treatment with rituximab;
    • If using treatment with pembrolizumab, women of childbearing potential should continue to follow contraceptive guidance during the treatment period and for at least 120 days after the last dose of study treatment;
    • Have a negative serum pregnancy test (sensitivity of at least 25 mIU/mL) at Screening; and have a negative serum or urine pregnancy test (Investigator’s discretion) within 72 hours prior to Cycle 1 Day -1 of study treatment (note that the screening serum pregnancy test can be used as the test prior to Day -1 study treatment if it is performed within the prior 72 hours);
    • Avoid conceiving for 8 weeks after the last dose of TJ011133;
    • Avoid donation of ova from signing the ICF until 8 weeks after the last dose of TJ011133 (12 months after the last dose of rituximab);
    • Agree to ongoing urine pregnancy testing, if clinically indicated, during the course of the study.
  • Males must agree to use a condom (a latex condom is recommended) during sexual contact with a pregnant female or a female of childbearing potential and will avoid donation of sperm or having a female partner conceive from the time of signing the ICF, while participating in the study, during dose interruptions, and for at least 90 days after the last dose of study treatment, even if he has undergone a successful vasectomy.
  • Subject with a QT interval corrected for heart rate using Fridericia's formula (QTcF) and/or QT interval corrected for heart rate using Bazett's formula of ≤ 450 msec for males, ≤ 470 msec for females.
  • No systemic anti-cancer therapy within 4 weeks of starting study treatment or at least 5 half-lives (whichever is shorter) before study drug administration, and all AEs have either resolved or stabilized.
    • Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
  • A 28-day washout period after the completion of programmed death-1 (PD-1)/PD-L1 therapy.
  • Adequate bone marrow function in subjects with solid tumors, including the following:
    • Part 1
    • Absolute neutrophil count ≥ 1500/μL (≥ 1.5 × 10^9 /L) without growth factor support for 7 days (14 days if on pegfilgrastim);
    • Platelet ≥ 100 × 10^3μL (≥ 100 ×10^9 /L) without transfusion within 2 weeks of the first study drug administration;
    • Hemoglobin ≥ 9 g/dL without transfusion within 2 weeks of the first study drug administration;
    • Part 2
    • Absolute neutrophil count ≥ 1500/μL (≥ 1.5 × 10^9 /L) without growth factor support for 7 days (14 days if on pegfilgrastim);
    • Platelet ≥ 75 × 10^3μL (≥ 75 × 109 /L) without transfusion within 2 weeks of the first study drug administration;
    • Hemoglobin ≥ 8 g/dL without transfusion within 2 weeks of the first study drug administration.
    • Adequate bone marrow function in subjects with NHL, including:
    • Part 1
    • Absolute neutrophil count ≥1000/μL (≥ 1.0 × 10^9 /L) without growth factor support for 7 days (14 days if on pegfilgrastim);
    • Platelet ≥ 100 × 10^3μL (≥ 100 × 10^9 /L) without transfusion within 2 weeks of the first study drug administration;
    • Hemoglobin ≥ 9 g/dL without transfusion within 2 weeks of the first study drug administration;
    • Part 2
    • Absolute neutrophil count ≥1000/μL (≥ 1.0 × 10^9 /L) without growth factor support for 7 days (14 days if on pegfilgrastim);
    • Platelet ≥ 50 × 10^3μL (≥ 50 ×10^9 /L) without transfusion within 2 weeks of the first study drug administration. For sites in China, Platelet ≥ 75 × 10^3μL (≥ 50 ×10^9 /L) without transfusion within 2 weeks of the first study drug administration;
    • Hemoglobin ≥ 8 g/dL without transfusion within 2 weeks of the first study drug administration. For sites in China, Hemoglobin ≥ 9 g/dL without transfusion within 2 weeks of the first study drug administration.
  • Adequate renal function and serum creatine ≤ 1.5 × ULN or estimated serum creatinine clearance of ≥60 mL/min using the Cockcroft-Gault equation.
  • Adequate liver function, including:
    • Total serum bilirubin ≤ 1.5 × ULN (≤ 3.0 × ULN if the subject has documented Gilbert syndrome);
    • AST and ALT ≤ 2.5 × ULN; ≤ 5.0 × ULN (if there is liver tumor present).
  • Normal parameters within the following (unless the subject is receiving anticoagulant therapy):
    • Prothrombin Time ≤ 1.5 ULN, or 11 to 15 seconds in the absence of a normal range;
    • Partial thromboplastin time or activated partial thromboplastin time ≤ 1.5 × ULN;
    • International normalized ratio ≤1.5 × ULN.
  • Resolved acute effects of any prior therapy to baseline severity or Grade ≤ 1 NCI CTCAE version 5.0 except for AEs not constituting a safety risk by Investigator judgment


Exclusion Criteria:

  • Has known active CNS metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are radiologically stable; i.e., without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
  • Subjects with Burkitt’s lymphoma, lymphoblastic lymphoma, Richter's transformation, primary effusion lymphoma or chronic lymphocytic leukemia/small lymphocytic lymphoma.
  • Subjects with mantle cell lymphoma with blastoid and TP53 alterations (applies to Part 1 only, all types of mantle cell lymphoma are excluded in Part 2).
  • Impaired cardiac function or clinically significant cardiac diseases, including any of the following:
    • Left ventricular ejection fraction 25% of the bone marrow (non-lymphoma subjects only), or any subject who has received prior radiotherapy within 2 weeks of the start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤ 2 weeks of radiotherapy) to non-CNS disease. For NSCLC subjects, radiation therapy to the lung that is > 30 Gy within 6 months of the first dose of trial treatment is not allowed (Parts 1B and Part 2 in combination with pembrolizumab only).
  • Prior treatment with CD47 or SIRPα inhibitors;
  • A woman of childbearing potential who has a positive urine pregnancy test (e.g., within 72 hours) prior to treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  • Pregnant or nursing females or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 8 weeks for TJ011133, 120 days for pembrolizumab and 12 months for rituximab after the last dose of study treatment.
  • Has a diagnosis of immunodeficiency (known active human immunodeficiency virus, hepatitis B virus/hepatitis C virus infection) or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug.
  • Blood product transfusions within 14 days of Cycle 1 Day 1.
  • Prior autologous stem cell transplant ≤3 months prior to starting TJ011133.
  • Prior allogeneic stem cell transplant with either standard or reduced intensity conditioning.
  • Has received chimeric antigen receptor (CAR) or chimeric antigen receptor T-cell (CAR-T) therapy within 90 days of starting TJ011133 OR has received prior CAR or CAR-T therapy and progressed within 90 days of infusion.
  • Has received any experimental antibodies or a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette–Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed.
  • Received any vaccine within 7 days of planned start of study therapy. Exceptions may apply with SARS-CoV-2 (COVID-19) vaccine, I-Mab Biopharma will provide up-to-date guidance based on evolving current practices.
  • History of AIHA or autoimmune thrombocytopenia.
  • Any bleeding history within 6 months of planned start of study therapy.
  • Any of the following in the previous 12 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, deep venous thrombosis, or pulmonary embolism.
  • Any other significant medical condition, laboratory abnormality, or psychiatric illness that places the subject at unacceptable risk or that would prevent the subject from complying with the study.
  • Second malignancy within the last 3 years (Part 2 dose expansion cohort only) with the exception of cutaneous squamous cell carcinoma or cutaneous basal cell carcinoma or cervical carcinoma in situ.
  • Active graft versus host disease (GVHD) or ongoing immunosuppression for GVHD.
  • Donation of blood from 3 months prior to Screening, plasma from 2 weeks prior to Screening, or platelets from 6 weeks prior to Screening.
  • Has severe hypersensitivity (≥ Grade 3) to pembrolizumab or rituximab and/or any of its excipients;
  • Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
  • Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
  • Has an active infection requiring systemic therapy.
  • Not recovered (i.e., to ≤ Grade 1 or to baseline) from AEs emerging from previous treatments (except alopecia or neuropathy).
  • Incomplete recovery from AEs and/or major surgery (must be ≤ Grade 1).
  • History of a ≥ Grade 3 irAE with prior immunotherapy with the exception of non-clinically significant laboratory abnormalities.
  • Unwilling or unable to comply with study procedures (including follow-up procedures).

Eligibility last updated 1/19/22. Questions regarding updates should be directed to the study team contact.

Biologic/Vaccine, Drug, Administration of antineoplastic agent, Drug therapy, Immunotherapy for cancer
Bladder cancer, Cancer, Diffuse large b-cell lymphoma, Fallopian tube cancer, Lung cancer, Lymphoma, Non-Hodgkin's lymphoma, Non-small cell lung cancer, Ovarian cancer, Peritoneal cancer, Tumors and masses
Biological therapy for cancer, Cancer treatment, Carcinoma of fallopian tube, Carcinoma of peritoneum, Diffuse non-Hodgkin's lymphoma, large cell (clinical), Hematopoietic system, Malignant epithelial tumor of ovary, Malignant tumor of fallopian tube, Malignant tumor of urinary bladder, Medical Oncology, Non-small cell lung cancer, Pembrolizumab [USAN:INN], Primary malignant neoplasm of bladder, Primary malignant neoplasm of the peritoneum, Reproductive system, Respiratory system, Rituximab, Secondary malignant neoplastic disease, Solid tumor configuration, Targeted drug therapy, Urinary system, pembrolizumab, rituximab
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APTO-CG-806-01: A Phase Ia/b Trial to Evaluate the Safety and Tolerability of CG-806 in Patients With CLL/SLL or Non-Hodgkin's Lymphomas

A Study of CG-806 in Patients with Relapsed or Refractory CLL/SLL or Non-Hodgkin's Lymphomas

Jose Villasboas Bisneto
All
18 years and over
Phase 1
This study is NOT accepting healthy volunteers
0000-101039-P01-RST
19-008026
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Inclusion Criteria:
 

  • Age ≥ 18 years  old.
  • Life expectancy of at least 2 months.
  • ECOG Performance Status ≤ 2.
  • Patients must be able to swallow capsules.
  • Adequate hematologic parameters, unless cytopenias are disease caused.
  • Adequate renal, liver and cardiac function parameters.


Exclusion Criteria:

  • Patients with GVHD requiring systemic immunosuppressive therapy.
  • Uncontrolled leptomeningeal disease, auto-immune hemolytic anemia and uncontrolled and clinical significant disease related metabolic disorde.r 
  • Clinically significant intravascular coagulation. 
  • Treatment with other investigational drugs within 14 days prior to first study treatment administration.
Drug, Radiation, Administration of antineoplastic agent, Drug therapy
Cancer, Chronic lymphocytic leukemia, Leukemia, Lymphoma, Macroglobulinemia, Non-Hodgkin's lymphoma, Recurrent cancer, Waldenstrom macroglobulinemia
CG-806, Cancer treatment, Chronic lymphoid leukemia, disease, Hematopoietic system, Malignant lymphoma - small lymphocytic, Medical Oncology, Non-Hodgkin's lymphoma (clinical), Waldenström macroglobulinemia
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Open label, multi-center, Phase 1b/2 clinical trial to evaluate the safety and efficacy of autologous CAR-BCMA T cells (CT053) in subjects with relapsed and/or refractory multiple myeloma (LUMMICAR STUDY 2)

Open-label, Multi-center, Phase 1b/2 Clinical Trial to Evaluate the Safety and Efficacy of Autologous CAR-BCMA T-cells (CT053) in Patients

Shaji Kumar
All
18 years to 80 years old
Phase 1/2
This study is NOT accepting healthy volunteers
0000-101045-P01-RST
19-007047
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Inclusion Criteria:

  • Voluntarily signed consent.
  • Age of ≥ 18 and ≤ 80 years.
  • Received sufficient prior lines of myeloma therapy.
  • Received treatment with at least one proteasome inhibitor, one IMiD and daratumumab.
  • The patients should have measurable disease per IMWG definition.
  • Estimated life expectancy > 12 weeks.
  • ECOG performance score 0-1.
  • Patients should have reasonable CBC counts, renal and hepatic functions.
  • Sufficient venous access for leukapheresis collection, and no other contraindications to leukapheresis.
  • Women of childbearing age must undergo a serum pregnancy test with negative results before screening, and are willing to use effective and reliable method of contraception for at least 6 months after T cell infusion.
  • Men must be willing to use effective and reliable method of contraception for at least 6 months after T cell infusion.


Exclusion Criteria:

  • Pregnant or lactating women.
  • HIV, active hepatitis C virus (HCV), or active hepatitis B virus (HBV) infection.
  • Any uncontrolled active infection.
  • AEs from previous treatment that have not recovered.
  • Patients who have had anti-BCMA therapy.
  • Patients who have graft versus host disease (GvHD).
  • Patients have received stem cell transplantation less than 12 weeks before leukapheresis.
  • Patients have received any anti-cancer treatment before leukapheresis.
  • Patients have received steroids before leukapheresis or lymphodepletion.
  • Patients have plasma cell leukemia, Waldenström macroglobulinemia, POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome or clinically significant symptomatic immunoglobulin light chain (AL) amyloidosis with evidence of end-organ damage.
  • Patients have been administered live attenuated vaccine before leukapheresis or lymphodepletion.
  • Patients allergic to Flu, Cy, tocilizumab, dimethyl sulfoxide (DMSO) or CT053 CAR BCMA T cell.
  • Patients have clinical significant cardiac conditions that researchers believe that participating in this clinical trial may endanger the health of the patients.
  • Patients have clinical significant pulmonary conditions.
  • Patients are known to have active autoimmune diseases including but not limited to psoriasis, rheumatoid arthritis and other needs of long-term immunosuppressive therapy.
  • Patients with second malignancies in addition to MM are not eligible.
  • Patients have central nervous system (CNS) metastases or CNS involvement.
  • Patients have significant neurologic disorders.
  • Patients are unable or unwilling to comply with the requirements of clinical trial.

Eligibility last updated 11/24/21. Questions regarding updates should be directed to the study team contact.

 

    Biologic/Vaccine, Administration of antineoplastic agent, Drug therapy, Immunotherapy for cancer
    Cancer, Multiple myeloma, Plasma cell disorders
    Biological therapy for cancer, Cancer treatment, Hematopoietic system, Immune system, Medical Oncology, Ningetinib, Relapse multiple myeloma, Cellular therapy
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    EAA173, Daratumumab to Enhance Therapeutic Effectiveness of Revlimid in Smoldering Myeloma (DETER-SMM) (DETER-SMM)

    A Study to Evaluate Lenalidomide and Dexamethasone, with or without Daratumumab, in Treating High-Risk Smoldering Myeloma Patients

    Taxiarchis Kourelis
    All
    18 years and over
    Phase 3
    This study is NOT accepting healthy volunteers
    0000-101050-P01-RST
    19-006110
    Show full eligibility criteria
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    Inclusion Criteria:
     

     

    • Patient must be ≥ 18 years of age.                    
    • Patient must be diagnosed with asymptomatic high-risk smoldering multiple myeloma (SMM) within the past 12 months. High-risk is defined by the presence of 2 or more of the following factors:
      • Abnormal serum free light chain (FLC) ratio of involved to uninvolved >20, but less than 100 if the involved FLC is >10 mg/dL by serum FLC assay;
      • Serum M-protein level > 2 gm/dL;
      • Presence of t(4;14) or del 17p or 1q gain by conventional cytogenetics or FISH studies;
      • > 20% plasma cells on biopsy or aspirate;
    • A bone marrow aspirate and/or biopsy is required to be performed within 28 days prior to randomization and must demonstrate 10-59% clonal plasma cells.
      1.  
    • Patient must have measureable disease as defined by having one or more of the following, obtained within 28 days prior to randomization:
      • ≥ 1 g/dL on serum protein electrophoresis;
      • ≥ 200 mg of monoclonal protein on a 24 hour urine protein electrophoresis.
    • NOTE: In the rare situation where the SPEP is felt to be unreliable, then quantitative immunoglobulin levels on nephelometry or turbidometry can be accepted. SPEP, UPEP, and serum FLC are required to be performed within 28 days prior to randomization.
    • NOTE:      UPEP (on a 24-hour collection) is required; no substitute method is acceptable. Urine must be followed monthly if the baseline urine M-spike is ≥ 200 mg/24 hr, and urine in addition to serum must be followed in order to confirm a VGPR or higher response.
    • Patient must have no lytic lesions, no known plasmacytoma, and no unexplained hypercalcemia (i.e., > 11 mg/dL or 1mg/dL above ULN). Specifically, local interpretation of MRI and PET scans will be used to exclude lytic lesions or plasmacytomas and must be obtained within 60 days prior to randomization.
    • Patient must not have known COPD with FEV1 < 50% or known moderate or severe persistent asthma within 2 years prior to randomization.
    • Patient must have adequate organ and marrow function as defined below (obtained within 28 days prior to randomization):
      • Hemoglobin ≥ 11 g/dL;
      • Platelet count ≥ 100,000 cells/mm^3;
      • Absolute neutrophil count ≥ 1500 cells/mm^3;
      • Calculated creatinine clearance ≥ 30 mL/min;
      • Bilirubin ≤ 1.5 mg/dL;
      • SGPT (ALT) and SGOT (AST) ≤ 2.5 times the upper limit of normal.
    • Patient must not have any prior or concurrent systemic or radiation therapy for the treatment of myeloma. Patient must also not have contraindication to DVT prophylaxis/aspirin.
    • Patient must not have more than one focal marrow lesion on MRI of either pelvis or spine.
    • Concurrent use of erythropoietin is not allowed while on study therapy.
    • Prior or glucocorticosteroid therapy for the treatment of multiple myeloma is not permitted.
    • Prior systemic glucocorticosteroid use for the treatment of non-malignant disorders is permitted; concurrent use after registration on the study should be restricted to the equivalent of prednisone 10 mg per day. Prior or concurrent topical or localized glucocorticosteroid therapy to treat non-malignant comorbid disorders is permitted.
    • Patient must not have active, uncontrolled seizure disorder. Patient must not have had a seizure in the last 6 months.
    • Patient must not have uncontrolled intercurrent illness including uncontrolled hypertension, symptomatic congestive heart failure, unstable angina, uncontrolled cardiac arrhythmia, uncontrolled psychiatric illness or social situation that would limit compliance with the study, or a prior history of Stevens Johnson Syndrome.
    • Patient must have an ECOG performance status 0, 1, or 2.
    • Patients with monoclonal gammopathy of undetermined significance are not eligible.
    • Patient must not have Grade 2 or higher peripheral neuropathy per CTCAE.
    • Patient must not have active, uncontrolled infection.
    • Patient may have a history of current or previous deep vein thrombosis or pulmonary embolism but are required to take some form of anti-coagulation as prophylaxis if they are not currently on full- dose anticoagulation.
    • Patient should not have New York Heart Association classification III or IV heart failure at baseline.
    • Patients with a history of prior malignancy are eligible provided they were treated with curative intent and have been free of disease for the time period considered appropriate for cure of the specific cancer.
    • Patient must agree to register into the mandatory REMS program and be willing and able to comply with the requirements of REMS.
    • Women must not be pregnant due to potential harm to the fetus from Daratumumab and Lenalidomide. All females of childbearing potential (FCBP) must have a blood test or urine study with a sensitivity of at least 25 mIU/mL within 10-14 days prior to the first dose of lenalidomide and again within 24 hours prior to the first dose of lenalidomide. FCBP must also agree to ongoing pregnancy testing while on treatment. A female of childbearing potential is defined as any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria:
      • has achieved menarche at some point;
      • has not undergone a hysterectomy or bilateral oophorectomy; or
      • has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).
      • Females of childbearing potential (FCBP) must either abstain from sexual intercourse for the duration of their participation in the study or agree to use TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME for 1) at least 28 days before starting study treatment; 2) while participating in the study; 3) during dose interruptions; and 4) for at least 28 days after the last dose of protocol treatment (FCBP who are assigned to Arm A and receive daratumumab must extend this contraception requirement to 3 months after the last dose of protocol treatment). Women must also agree to not breastfeed during this same time period. Men must agree to either abstain from sexual intercourse for the duration of their participation in the study or use a latex condom during sexual contact with a FCBP while participating in the study and for 28 days after the last dose of protocol treatment even if they have had a successful vasectomy (Men assigned to Arm A and receive daratumumab must extend this contraception requirement to 3 months after the last dose of protocol treatment).
      • Men must also agree to abstain from donating sperm while on study treatment and for 28 days after the last dose of protocol treatment even if they have had a successful vasectomy. Both women and men must both agree to abstain from donating blood during study participation and for at least 28 days after the last dose of protocol treatment.
      • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of randomization are eligible for this trial. 
      • Patient should not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to daratumumab, lenalidomide, or dexamethasone.
      • For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
      • Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.

     

    Biologic/Vaccine, Drug, Other, Administration of antineoplastic agent, Chemotherapy, Drug therapy, Immunotherapy for cancer
    Cancer, Multiple myeloma, Plasma cell disorders
    Biological therapy for cancer, Cancer treatment, Chemotherapy, Daratumumab [USAN:INN], Dexamethasone, Hematopoietic system, Immune system, Lenalidomide, Medical Oncology, Smoldering myeloma, Targeted drug therapy, daratumumab, dexamethasone, lenalidomide
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    Mayo Clinic — Rochester, MN

    EAA173, Daratumumab to Enhance Therapeutic Effectiveness of Revlimid in Smoldering Myeloma (DETER-SMM)

    A Study to Evaluate Lenalidomide and Dexamethasone, with or without Daratumumab, in Treating High-Risk Smoldering Myeloma Patients

    Mina Hanna
    All
    18 years and over
    Phase 3
    This study is NOT accepting healthy volunteers
    0000-101050-P01-ALCL
    19-006110
    Show full eligibility criteria
    Hide eligibility criteria

    Inclusion Criteria:
     

     

    • Patient must be ≥ 18 years of age.                    
    • Patient must be diagnosed with asymptomatic high-risk smoldering multiple myeloma (SMM) within the past 12 months. High-risk is defined by the presence of 2 or more of the following factors:
      • Abnormal serum free light chain (FLC) ratio of involved to uninvolved >20, but less than 100 if the involved FLC is >10 mg/dL by serum FLC assay;
      • Serum M-protein level > 2 gm/dL;
      • Presence of t(4;14) or del 17p or 1q gain by conventional cytogenetics or FISH studies;
      • > 20% plasma cells on biopsy or aspirate;
    • A bone marrow aspirate and/or biopsy is required to be performed within 28 days prior to randomization and must demonstrate 10-59% clonal plasma cells.
      1.  
    • Patient must have measureable disease as defined by having one or more of the following, obtained within 28 days prior to randomization:
      • ≥ 1 g/dL on serum protein electrophoresis;
      • ≥ 200 mg of monoclonal protein on a 24 hour urine protein electrophoresis.
    • NOTE: In the rare situation where the SPEP is felt to be unreliable, then quantitative immunoglobulin levels on nephelometry or turbidometry can be accepted. SPEP, UPEP, and serum FLC are required to be performed within 28 days prior to randomization.
    • NOTE:      UPEP (on a 24-hour collection) is required; no substitute method is acceptable. Urine must be followed monthly if the baseline urine M-spike is ≥ 200 mg/24 hr, and urine in addition to serum must be followed in order to confirm a VGPR or higher response.
    • Patient must have no lytic lesions, no known plasmacytoma, and no unexplained hypercalcemia (i.e., > 11 mg/dL or 1mg/dL above ULN). Specifically, local interpretation of MRI and PET scans will be used to exclude lytic lesions or plasmacytomas and must be obtained within 60 days prior to randomization.
    • Patient must not have known COPD with FEV1 < 50% or known moderate or severe persistent asthma within 2 years prior to randomization.
    • Patient must have adequate organ and marrow function as defined below (obtained within 28 days prior to randomization):
      • Hemoglobin ≥ 11 g/dL;
      • Platelet count ≥ 100,000 cells/mm^3;
      • Absolute neutrophil count ≥ 1500 cells/mm^3;
      • Calculated creatinine clearance ≥ 30 mL/min;
      • Bilirubin ≤ 1.5 mg/dL;
      • SGPT (ALT) and SGOT (AST) ≤ 2.5 times the upper limit of normal.
    • Patient must not have any prior or concurrent systemic or radiation therapy for the treatment of myeloma. Patient must also not have contraindication to DVT prophylaxis/aspirin.
    • Patient must not have more than one focal marrow lesion on MRI of either pelvis or spine.
    • Concurrent use of erythropoietin is not allowed while on study therapy.
    • Prior or glucocorticosteroid therapy for the treatment of multiple myeloma is not permitted.
    • Prior systemic glucocorticosteroid use for the treatment of non-malignant disorders is permitted; concurrent use after registration on the study should be restricted to the equivalent of prednisone 10 mg per day. Prior or concurrent topical or localized glucocorticosteroid therapy to treat non-malignant comorbid disorders is permitted.
    • Patient must not have active, uncontrolled seizure disorder. Patient must not have had a seizure in the last 6 months.
    • Patient must not have uncontrolled intercurrent illness including uncontrolled hypertension, symptomatic congestive heart failure, unstable angina, uncontrolled cardiac arrhythmia, uncontrolled psychiatric illness or social situation that would limit compliance with the study, or a prior history of Stevens Johnson Syndrome.
    • Patient must have an ECOG performance status 0, 1, or 2.
    • Patients with monoclonal gammopathy of undetermined significance are not eligible.
    • Patient must not have Grade 2 or higher peripheral neuropathy per CTCAE.
    • Patient must not have active, uncontrolled infection.
    • Patient may have a history of current or previous deep vein thrombosis or pulmonary embolism but are required to take some form of anti-coagulation as prophylaxis if they are not currently on full- dose anticoagulation.
    • Patient should not have New York Heart Association classification III or IV heart failure at baseline.
    • Patients with a history of prior malignancy are eligible provided they were treated with curative intent and have been free of disease for the time period considered appropriate for cure of the specific cancer.
    • Patient must agree to register into the mandatory REMS program and be willing and able to comply with the requirements of REMS.
    • Women must not be pregnant due to potential harm to the fetus from Daratumumab and Lenalidomide. All females of childbearing potential (FCBP) must have a blood test or urine study with a sensitivity of at least 25 mIU/mL within 10-14 days prior to the first dose of lenalidomide and again within 24 hours prior to the first dose of lenalidomide. FCBP must also agree to ongoing pregnancy testing while on treatment. A female of childbearing potential is defined as any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria:
      • has achieved menarche at some point;
      • has not undergone a hysterectomy or bilateral oophorectomy; or
      • has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).
      • Females of childbearing potential (FCBP) must either abstain from sexual intercourse for the duration of their participation in the study or agree to use TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME for 1) at least 28 days before starting study treatment; 2) while participating in the study; 3) during dose interruptions; and 4) for at least 28 days after the last dose of protocol treatment (FCBP who are assigned to Arm A and receive daratumumab must extend this contraception requirement to 3 months after the last dose of protocol treatment). Women must also agree to not breastfeed during this same time period. Men must agree to either abstain from sexual intercourse for the duration of their participation in the study or use a latex condom during sexual contact with a FCBP while participating in the study and for 28 days after the last dose of protocol treatment even if they have had a successful vasectomy (Men assigned to Arm A and receive daratumumab must extend this contraception requirement to 3 months after the last dose of protocol treatment).
      • Men must also agree to abstain from donating sperm while on study treatment and for 28 days after the last dose of protocol treatment even if they have had a successful vasectomy. Both women and men must both agree to abstain from donating blood during study participation and for at least 28 days after the last dose of protocol treatment.
      • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of randomization are eligible for this trial. 
      • Patient should not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to daratumumab, lenalidomide, or dexamethasone.
      • For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
      • Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.

     

    Biologic/Vaccine, Drug, Other, Administration of antineoplastic agent, Chemotherapy, Drug therapy, Immunotherapy for cancer
    Cancer, Multiple myeloma, Plasma cell disorders
    Biological therapy for cancer, Cancer treatment, Chemotherapy, Daratumumab [USAN:INN], Dexamethasone, Hematopoietic system, Immune system, Lenalidomide, Medical Oncology, Smoldering myeloma, Targeted drug therapy, daratumumab, dexamethasone, lenalidomide
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    Mayo Clinic Health System — Albert Lea, MN

    (ECTx) HPN536-2001: A Phase 1/2a Open-label, Multicenter, Dose Escalation and Dose Expansion Study of the Safety, Tolerability, and Pharmacokinetics of HPN536 in Patients with Advanced Cancers Associated with Mesothelin Expression Who Have Failed Standard Available Therapy

    Study of HPN536 in Patients with Advanced Cancers Associated With Mesothelin Expression

    Andrea Wahner Hendrickson
    All
    18 years and over
    Phase 1/2
    This study is NOT accepting healthy volunteers
    0000-101055-P01-RST
    19-006158
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    Inclusion Criteria:

    • Patients ≥ 18 years of age.
    • One of the following progressive advanced or metastatic cancers:
      • Epithelial ovarian, fallopian tube, or primary peritoneal cancer (Part 1 and Part 2, Group 1 only) that is platinum refractory or platinum resistant;
      • Pancreatic adenocarcinoma (Part 2, Group 2 only) that is locally advanced, and now with progressive disease on or after front-line treatment;
      • Malignant mesothelioma with epithelioid histology, pleural or primary peritoneal (Part 2, Group 3 only) that is progressive disease following frontline platinum-based chemotherapy;
      • For Part 2 only
        •Measurable disease according to RECIST v1.1 for patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer, pancreatic adenocarcinoma, and peritoneal mesothelioma, and mRECIST v1.1 for patients with pleural mesothelioma;
      • Available archival tissue sample or fresh biopsy tissue sample must be obtained prior to enrollment;
      • For patients previously treated with systemic chemotherapy, targeted therapy, immunotherapy, or treatment with an investigational anticancer agent, discontinuation must have occurred ≥ 2 weeks, or at least 5 half-lives, whichever is longer, prior to start of study drug. The maximum washout period will not exceed 4 weeks;
      • ECOG performance status of 0 or 1;
      • Adequate bone marrow function, including:
        • Absolute neutrophil count (ANC) ≥ 1500/mm^3 or ≥ 1.5 x 10^9/L;
        • Platelets ≥ 100,000/mm3 or ≥ 100 x 10^9/L;
        • Hemoglobin (Hgb) ≥ 0 g/dL.
      • Adequate renal function, including estimated creatinine clearance ≥ 50 mL/min;
      • Adequate liver function, including:
        • Total serum bilirubin ≤ 1.5 x upper limit of normal (ULN) unless the patient has documented Gilbert syndrome in which case the maximum total serum bilirubin should be < 5 mg/dL;
        • Aspartate and alanine transaminase (AST and ALT) ≤ 2.5 x ULN or AST/ALT ≤ 5 x ULN for patients with liver metastases.
      • Serum albumin ≥ 30 mg/mL.


    Exclusion Criteria:

    • Previously treated or current brain metastases.
      • Note: Patients with previously treated brain metastases may participate provided they are clinically stable for at least 4 weeks prior to study entry and have no evidence of new or enlarging brain metastases.
    • Concurrent treatment with anti- TNFα therapies, systemic corticosteroids, or other immune suppressive drugs within the 2 weeks prior to Screening.
    • History of or known or suspected autoimmune disease.
    • History of clinically significant cardiovascular disease.
    • Second primary malignancy that has not been in remission for greater than 3 years.
    • Pulmonary, hematologic, renal, hepatic, gastrointestinal, neurological or psychiatric disease that would limit compliance with study requirements
    Biologic/Vaccine, Administration of antineoplastic agent, Drug therapy
    Cancer
    Biological therapy for cancer, Cancer treatment, Gene expression, Malignant neoplastic disease, Medical Oncology, Cellular therapy
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    Mayo Clinic — Rochester, MN

    A Phase 1, Open-Label, Dose-Escalation and Expansion, Multicenter Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of MT-0169 in Patients with Relapsed or Refractory Multiple Myeloma or Non-Hodgkin Lymphoma

    A Study of MT-0169 in Participants With Relapsed or Refractory Multiple Myeloma or non-Hodgkin Lymphoma

    Shaji Kumar
    All
    18 years and over
    Phase 1
    This study is NOT accepting healthy volunteers
    0000-101056-P01-RST
    19-007127
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    Inclusion Criteria
    •Part 1:

    • Patients must be informed about the study and fully consent to participation as demonstrated by signing the written informed consent form (ICF) before any screening procedures.
    • Male or female patients 18 years or older at the time of consent.
    • Confirmed diagnosis of MM per the revised IMWG diagnostic criteria.
    • Patients with RRMM who have failed treatment with, are intolerant to, or are not candidates for available therapies that are known to confer clinical benefit.
    • Must meet all of the following criteria for prior therapy:
      • Must be refractory to ≥ 1 proteasome inhibitor (PI), ≥ 1 immunomodulatory drug (IMiD), and ≥ 1 steroid;
      • Must either have received ≥ 3 prior lines of therapy or ≥ 2 prior lines of therapy if 1 line included a combination of PI and IMiD (prior treatment with an anti-CD38 therapy is permitted).
    • With measurable disease, defined as ≥ 1 of the following:
      • Serum M-protein ≥ 500 mg/dL (≥ 5 g/L) on serum protein electrophoresis (SPEP);
      • Urine M-protein ≥ 200 mg/24 h on urine protein electrophoresis (UPEP).
      • Serum FLC assay result with an involved FLC level ≥ 10 mg/dL (≥ 100 mg/L) if serum FLC ratio is abnormal.
    • Patients with serum M-protein, urine M-protein, or involved immunoglobulin FLC not meeting the measurable disease criteria above will be eligible if they have ≥ 1 of the following:
      • PET imaging with ≥ 1 plasmacytoma lesion with a single diameter of ≥ 2cm;
      • Bone marrow (BM) aspirate/biopsy with plasma cell percentage ≥ 30%
    • With Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1.
    • With normal QT interval corrected by the Fridericia method (QTcF) on screening electrocardiogram (ECG)[ QTcF of ≤ 450 millisecond (ms) in males or ≤ 470 ms in females].
    • Must meet the following clinical laboratory criteria at entry:
      • Total bilirubin ≤1.5 x the upper limit of the normal range (ULN), except for Gilbert's syndrome (direct bilirubin must be < 2.0 x ULN);
      • Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≤ 2.5 x ULN;
      • Estimated glomerular filtration rate (eGFR) ≥ 30 (mL/min/1.73 square meter [m^2]), using the modification of diet in renal disease (MDRD) equation;
      • Absolute neutrophil count (ANC) ≥ 1000 per cubic millimeter (/mm^3) (≥ 1.0*10^9 per liter [/L]); ≥ 750/mm^3 (≥ 0.75 x 10^9/L) may be acceptable for participants with > 50% of plasma cells in BM;
      • Platelet count ≥ 75,000/ mm^3 (≥ 75 x 10^9/L); ≥ 50,000/ mm^3 (≥ 50 X 10^9/L) may be acceptable for participants with > 50% of plasma cells in BM;
      • Hemoglobin ≥ 7.5 g/dL without transfusion within 7 days before the lab test;
      • Serum albumin ≥ 2.5 g/dL.
    • Female patients who:
      • are postmenopausal for at least 1 year prior to screening; OR
      • are surgically sterile; OR
      • If they are of childbearing potential, agree to practice 1 highly effective method of contraception and 1 additional effective barrier method at the same time from study entry through 30 days after the last dose of study drug; OR
      • agree to practice true abstinence if in line with the preferred and usual lifestyle [periodic abstinence (e.g., calendar, ovulation, symptothermal, postovulation methods), withdrawal, spermicides only, and lactational amenorrhea are not acceptable. Female and male condoms should not be used together].
    • Male patients, even if surgically sterilized (postvasectomy) who:
      • Agree to practice effective barrier contraception during the entire study and through 90 days after the last dose of study drug; OR
      • Agree to practice true abstinence if in line with the preferred and usual lifestyle [periodic abstinence (e.g., calendar, ovulation, symptothermal, postovulation methods), withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods. Female and male condoms should not be used together].

    Inclusion Criteria Part 2 (both RRMM and RRNHL patients):

    • ECOG performance score of 0 or 1.
    • Normal QTcF on screening ECG, defined as QTcF of ≤ 450 ms in males or ≤ 470 ms in females.
    • Must meet the following clinical laboratory criteria at study entry:
      • Total bilirubin ≤ 1.5 x the ULN, except for Gilbert's syndrome (direct bilirubin must be < 2.0 x ULN);
      • Serum ALT and AST ≤ 2.5 x ULN;
      • eGFR ≥ 30 mL/min/1.73 m^2(MDRD equation);
      • ANC ≥ 1000 mm^3 (≥ 1.0 x 10^9 /L); a count of ≥ 750/mm^3 (≥ 0.75 x 10^9/L) may be acceptable for participant with > 50% of plasma cells in BM;
      • Platelet count ≥ 75,000/ mm63 (≥ 75 x 10^9/L); a value of ≥ 50,000/ mm3(≥ 50 x 10^9/L) may be acceptable for participants with > 50% of plasma cells in BM;
      • Hemoglobin ≥ 7.5 g/dL without transfusion within 7 days before the lab test;
      • Serum albumin ≥ 2.5 g/dL.
    • Female patients who:
      • are postmenopausal for at least 1 year prior to screening; OR
      • are surgically sterile; OR
      • If they are of childbearing potential, agree to practice 1 highly effective method of contraception and 1 additional effective barrier method at the same time from study entry through 30 days after the last dose of study drug; OR
      • agree to practice true abstinence if in line with the preferred and usual lifestyle [periodic abstinence (e.g., calendar, ovulation, symptothermal, postovulation methods), withdrawal, spermicides only, and lactational amenorrhea are not acceptable. Female and male condoms should not be used together].
    • Male patients, even if surgically sterilized (postvasectomy) who:
      • Agree to practice effective barrier contraception during the entire study and through 90 days after the last dose of study drug; OR
      • Agree to practice true abstinence if in line with the preferred and usual lifestyle [periodic abstinence (e.g., calendar, ovulation, symptothermal, postovulation methods), withdrawal, spermicides only, and lactational amenorrhea are not acceptable. Female and male condoms should not be used together].

    Inclusion Criteria Part 2 for RRNHL patients:

    • Pathologically confirmed diagnosis of the following NHL subtype based on local pathology report:
      • Mantle cell lymphoma (MCL) - Nodal MCL;
      • Diffuse large B-cell lymphoma (DLBCL), DLBCL- NOS, Plasmablastic lymphoma (PbL), Primary effusion lymphoma (PEL),  Primary effusion lymphoma (PMBL);
      • Follicular lymphoma;
      • Burkitt lymphoma (BL);
      • Peripheral T-cell lymphoma (PTCL) - PTCL-NOS (eligible at MTD/RPTD if biopsy evidence of CD38 positivity), Angioimmunoblastic T-cell lymphoma (AITL);
      • Extranodal NK/T-cell lymphoma (ENKTL)-nasal type.
    • RRNHL, having failed treatment with, is intolerant to, or is determined not to be a candidate for available therapies considered standard of care (SOC) or are known to confer clinical benefit.
    • At least 1 measurable site of disease according to the Lugano classification for lymphoma:
      • A measurable nodal lesion with longest diameter (LDi) greater than 1.5cm; OR
      • A measurable extranodal lesion with LDi greater than 1.0cm.
    • Evidence of a CD38 positive tumor. Any of the following are acceptable:
      • Evidence of CD38 expression from most recent biopsy or blood sample [either flow cytometry (FCM) or immunohistochemistry (IHC)]; OR
      • The most recently archived tissue assessed for CD38 expression by IHC; OR
      • Fresh biopsy for CD38 expression assessment by IHC within 35 days of Cycle 1 Day 1; OR
      • Fresh blood sample with circulating NHL cells assessed by FCM within 35 days of Cycle 1 Day 1 (BM biopsy excisional lymph node biopsy, core biopsy of any involved organ are all acceptable methods, find needle aspirate is not. Any level of positive CD38 expression is eligible).

    Inclusion Criteria Part 2 for RRMM patients:

    • Confirmed diagnosis of MM per IMWG diagnosis criteria:
      • RRMM, having failed treatment with, is intolerant to, or is determined not to be a candidate for available therapies considered SOC or are known to confer clinical benefit.
    • Must meet the following criteria for prior therapy:
      • Refractory or intolerant to ≥1 PI and ≥ 1 IMiD;
      • Receipt of ≥ 3 prior lines of therapy or ≥ 2 prior lines of therapy if 1 of those lines included a combination of a PI or IMiD (prior treatment with anti-CD38 therapy is permitted except for patients enrolled in the anti-CD38 therapy naïve cohort);
      • Daratumumab RR cohorts: RR to daratumumab at any time during treatment. Patients RR to other anti-CD38 therapies are excluded;
      • Anti-CD38 therapy naïve cohort: must not have received any prior anti CD-38 therapy.
    • Measurable disease, defined as ≥ 1 of the following:
      • Serum M-protein ≥ 50 mg/dL (≥ 5 g/L) on SPEP;
      • Urine M-protein ≥ 200 mg/24 hours on UPEP.;
      • Serum FLC assay result with and involved FLC level ≥ 10 mg/dL (≥ 100mg/L), provided the serum FLC ratio is abnormal.
    • Serum M-protein, urine M-protein or involved immunoglobulin FLC not meeting measurable disease criteria if at least 1 of the following criteria is met:
      • BM aspirate/biopsy showing plasma cell percentage ≥ 30%;
      • PET imaging showing at least 1 plasmacytoma lesion with a single diameter ≥ 2 cm.

    Exclusion Criteria for Part 1 (RRMM patients only):

    • With polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes (POEMS) syndrome, monoclonal gammopathy of unknown significance, smoldering myeloma, solitary plasmacytoma, amyloidosis, Waldenström macroglobulinemia, or Immunoglobulin M (IgM) myeloma.
    • With sensory or motor neuropathy of NCI CTCAE V5 Grade ≥ 3.
    • Have received final dose of any of the following treatments/procedures within the following interval before the first dose of MT-0169:
      • Myeloma-specific therapy, including PIs and IMiDs: 14 days;
      • Anti-CD38 (a) therapy: Isatuximab 90 days; daratumumab 60 days;
      • Corticosteroid therapy for myeloma: 7 days;
      • Radiation therapy for localized bone lesions: 14 days;
      • Major surgery:30 days;
      • Autologous stem cell transplant: 90 days;
      • Investigational therapy: 30 days.
    • Have received an allogeneic stem cell transplant or organ transplantation.
    • Have not recovered to Grade ≤ 1 or baseline, from adverse reactions to prior myeloma treatment or procedures (chemotherapy, immunotherapy, radiation therapy) excluding alopecia and Grade 2 neuropathy.
    • With clinical signs of central nervous system (CNS) involvement of MM.
    • With a history of myelodysplastic syndrome or another malignancy other than MM except for the following: any malignancy that has been in complete remission for 3 years, adequately treated local basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ, superficial bladder cancer, or asymptomatic prostate cancer without known metastatic disease and not requiring therapy or requiring only hormonal therapy and with normal prostate-specific antigen level for ≥ 1 year before the start of study therapy.
    • With known or suspected light chain amyloidosis of any organ (amyloid on the BM biopsy without other evidence of amyloidosis is acceptable).
    • With any of the following cardiovascular conditions:
      • Congestive heart failure (NYHA) class ≥ II or left ventricular ejection fraction (LVEF < 40%, cardiac myopathy, active ischemia, or any other uncontrolled cardiac condition such as angina pectoris or myocardial infarction or clinically significant arrhythmia requiring therapy including anticoagulants within the past 6 months or at screening;
      • Resting tachycardia (heart rate of > 100 bpm) at screening;
      • Clinically significant uncontrolled hypertension at screening;
      • Cardiac MRI at screening demonstrates evidence of infiltrative disease of the myocardium.
    • With a history of document significant pleural or pericardial effusions within 3 months before the start of treatment, including:
      • Pericarditis (any Grade);
      • Pericardial effusion (Grade ≥ 2);
      • Non-malignant pleural effusion (Grade ≥ 2);
      • Malignant pleural effusion (Grade ≥ 2).
    • Patients with a history of noncardiogenic pulmonary edema associated with diffuse peripheral edema and a history of intravascular hypovolemia associated with systemic antineoplastic therapy.
    • With chronic or active infection requiring systemic therapy, history of symptomatic viral infection that has not been fully cured.
      • With HIV and an undetectable viral load and CD4+ T-cell (CD4+) counts ≥ 350 cells/mL may be allowed but patient must be taking appropriate opportunistic infection prophylaxis if clinically relevant;
      • With positive HBV serology may be allowed if undetectable viral load, receiving antiviral prophylaxis for potential HBV reactivation per institutional guidelines;
      • With positive HCV serology may be allowed if quantitative PCR for plasma HCV RNA is below the lower limit of detection. Concurrent antiviral HCV treatment per institutional guidelines is allowed.
    • Have received a live attenuated vaccine within 28 days of first dose of MT-0169.
    • With a history of ≥ Grade 2 systemic inflammatory response syndrome (SIRS)/ cytokine release syndrome (CRS) reactions following infusion with any monoclonal antibodies or Chimeric Antigen Receptor (CAR) T therapy.
    • With a chronic condition requiring systemic corticosteroids at > 10 mg/day of prednisone or equivalent.
    • Are lactating and breastfeeding or have a positive serum pregnancy test during the screening period or patients of reproductive potential who are not employing an effective birth control.
    • With a concurrent medical or psychiatric illness that would preclude study conduct and assessment including, but not limited to, uncontrolled medical conditions, uncontrolled and active infection, uncontrolled risk of bleeding, uncontrolled diabetes mellitus, pulmonary disease, alcoholic liver disease, or primary biliary cirrhosis.
    • With known allergy or intolerance to any of the drugs used in the study or excipients in the MT-0169 formulation.
    • With a history of hypersensitivity or serious toxic reaction to kanamycin or another aminoglycoside.

    Exclusion Criteria for Part 2 NHL patients only:

    • With known CNS lymphoma (exception allowed if history of CNS disease and evidence of SD on neuroimaging separated in time by at least 4 weeks and within 4 weeks of Cycle 1 Day 1).   
    • Have received a final dose of any of the following treatments/procedures within the following minimum interval before the first dose of MT-0169:
      • Nitrosoureas: 6 weeks;
      • Chemotherapy: 4 weeks;
      • Small molecules (< 0.9 kDa): 5 half-lives or at least 2 weeks:
      • Therapeutic antibodies: 4 weeks;
      • Radio/toxin -immunoconjugates: 12 weeks;
      • Radiation therapy to a target lesion (measurable disease): 4 weeks
      • Radiation therapy to a nontarget lesion (radiation therapy to non-target lesions may be permitted): 2 weeks
      • Investigational chemotherapeutic agents or antibodies: 4 weeks
      • Daratumumab: 60 days
      • Isatuximab: 90 days
      • (MCL) Bruton's tyrosine kinase inhibitors: 2 weeks or 5 half-lives, whichever is longer
      • Major surgery (determined by the principal investigator with the Sponsor): 4 weeks
      • Autologous stem cell transplant: 100 days
      • Allogenic stem cell transplant: 180 days (patients with graft vs host disease > Grade 1 will be excluded).
    • With a history of myelodysplastic syndrome or malignancy (other than NHL) except for the following: any malignancy in complete remission for 3 years, adequately treated local basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ, superficial bladder cancer, or asymptomatic prostate cancer without known metastatic disease and not requiring therapy or requiring only hormonal therapy and with normal prostate-specific antigen level for ≥ 1 year before the start of study therapy.

    Exclusion Criteria for Part 2 RRMM patients only:

    • With POEMS syndrome, monoclonal gammopathy of unknown significance, smoldering myeloma, solitary plasmacytoma, amyloidosis, Waldenström macroglobulinemia, IgM myeloma.
    • Have received a final dose of any of the following treatments/procedures within the following interval before the first dose of MT-0169:
      • Myeloma-specific therapy, including PIs and IMiDs: 14 days;
      • Anti-CD38 therapy
        •Isatuximab: 90 days;
      • Anti-CD38 therapy
        •Daratumumab: 60 days;
      • Corticosteroid therapy for myeloma: 7 days;
      • Radiation therapy for localized bone lesions: 14 days;
      • Major surgery: 30 days;
      • Autologous stem cell transplant: 90 days;
      • Investigational therapy: 30 days.
    • Have received an allogenic stem cell or organ transplant.
    • With clinical signs of CNS involvement of MM.
    • With a history of myelodysplastic syndrome or another malignancy other than MM except or any malignancy in complete remission for 3 years, adequately treated local basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ, superficial bladder cancer, or asymptomatic prostate cancer without known metastatic disease and not requiring therapy or requiring only hormonal therapy and with normal prostate-specific antigen level for >1 year before the start of study therapy.
    • With known or suspected light chain amyloidosis of any organ (amyloid on BM biopsy without other evidence of amyloidosis is acceptable).

    Exclusion Criteria for Part 2 (both RRMM and NHL patients):

     

    • Failed to recover to Grade ≤ 1 or baseline from adverse reactions to prior treatment or procedures (chemotherapy, immunotherapy, radiation therapy) excluding alopecia and stable Grade 2 neuropathy.
    • With any of the following cardiovascular conditions:
      • Congestive heart failure (NYHA) class ≥ II LVEF < 40%, cardiac myopathy, active ischemia, or any other uncontrolled cardiac condition such as angina pectoris or myocardial infarction or clinically significant arrhythmia requiring therapy including anticoagulants within the past 6 months or at screening;
      • Resting tachycardia (heart rate of >100 bpm) at screening;
      • Clinically significant uncontrolled hypertension at screening;
      • Cardiac MRI at screening demonstrating infiltrative disease of the myocardium 12. With a history of documented significant pleural or pericardial effusions, specifically any of the following within 3 months before the start of study treatment:
      • Pericarditis (any grade);
      • Pericardial effusion (Grade ≥ 2);
      • Non-malignant pleural effusion (Grade ≥ 2); OR
      • Malignant pleural effusion (Grade ≥ 3).
    • With a history of noncardiogenic pulmonary edema associated with peripheral edema and a history of intravascular hypovolemia associated with antineoplastic therapy.
    • With chronic or active infection requiring systemic therapy and a history of symptomatic viral infection that is not fully controlled or cured. The following exceptions apply for those with positive serologies of HIV, HBV, or HCV:
      • With HIV and undetectable viral load and CD4+ T-cell (CD4+) counts ≥ 350 cells/mL may be enrolled, but must be taking appropriate opportunistic infection prophylaxis, if clinically relevant;
      • With positive HBV serology are eligible if they have an undetectable viral load and the patient will receive antiviral prophylaxis for potential HBV reactivation per institutional guidelines;
      • With positive HCV serology are eligible if qPCR for plasma HCV RNA is below the lower limit of detection. Concurrent antiviral HCV treatment per institutional guidelines is allowed.
    • Have received a live attenuated vaccine within 28 days of the first dose of MT-0169.
    • With a history of Grade ≥ 2 SIRS/CRS reactions following infusion with any mAbs or CAR T therapy.
    • With a chronic condition requiring systemic corticosteroids ≥ 10 mg/day of prednisone or equivalent.
    • With a known allergy or intolerance to any of the drugs in the study or excipients in the MT-0169 formulation.
    • Are lactating and breastfeeding or have a positive serum pregnancy test during the screening period or male or female patients of reproductive potential who are not employing effective birth control.
    • With a concurrent medical or psychiatric illness that would preclude study conduct and assessment including, but not limited to, uncontrolled medical conditions, uncontrolled and active infection, uncontrolled risk of bleeding, uncontrolled diabetes mellitus, pulmonary disease, alcoholic liver disease, or primary biliary cirrhosis.
    • With a history of hypersensitivity or serious toxic reactions to kanamycin or another aminoglycoside.

     

    Drug, Administration of antineoplastic agent, Drug therapy
    Cancer, Multiple myeloma
    Cancer treatment, Hematopoietic system, Medical Oncology, Relapse multiple myeloma
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    Mayo Clinic — Rochester, MN

    S1803, Phase III Study of Daratumumab/rHuPH20 (NSC-810307) Lenalidomide or Lenalidomide as Post-Autologous Stem Cell Transplant Maintenance Therapy in Patients With Multiple Myeloma (MM) Using Minimal Residual Disease to Direct Therapy Duration (DRAMMATIC Study) (DRAMMATIC)

    A Study to Evaluate Daratumumab/rHuPh20 +/- Lenalidomide as Post-ASCT Maintenance for Multiple Myeloma with Minimal Residual Disease (MRD) to Direct Therapy Duration

    Rahma Warsame
    All
    18 years to 75 years old
    Phase 3
    This study is NOT accepting healthy volunteers
    0000-101060-P01-RST
    19-009968
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    Registration Step 1
    •Study Entry Post-Induction and Pre-Maintenance

    • Except where otherwise indicated below that test is required in a shorter timeframe, all tests for establishing baseline disease status must be completed within 60 days prior to registration. All test results must be documented on the Baseline Tumor Assessment Form for Multiple Myeloma and the Onstudy Form.

    Inclusion Criteria:

    • Patients must have had a confirmed diagnosis of symptomatic multiple myeloma that required systemic induction therapy prior to autologous stem cell transplantation (ASCT). Patients with smoldering myeloma are not eligible. Patients with purely nonsecretory MM as measured by electrophoresis and immunofixation and the absence of Bence Jones proteins in the urine are not eligible.
    • Patients must have measurable M protein in the serum (defined as ≥ 0.5g/dL) or urine (defined as ≥ 200 mg/24h). Patients with plasma cell leukemia are not eligible. Patients with disease measurable by serum light chain assay alone are eligible (defined as ≥ 100 mg/L on involved light chain).
    • Patients must not have any organ involvement by amyloidosis or evidence of amyloidosis related organ dysfunction.
    • Patients must not have progressive disease at any time prior to registration.
    • Patients must not be refractory to either lenalidomide or daratumumab/rHuPH20. 
    • Patients must not be intolerant to either lenalidomide or daratumumab/rHuPH20.
    • Patients must have initiated induction therapy within 12 months prior to registration Step 1 and have received at least two cycles of induction therapy.
    • Patients must be registered to Step 1 prior to registration to Step 2. Registration to Step 1 may take place prior to or after autologous stem cell transplant (ASCT), but after completion of induction therapy.
    • Patients must not have received any investigational agents within 14 days prior to registration.
    • Patients must be willing and able to take DVT prophylaxis (aspirin, low molecular weight heparin, warfarin, or equivalent oral anticoagulation).
    • Patients must be ≥ 18 and ≤ 75 years of age at time of registration to Step 1.
    • Patients must have history and physical exam within 28 days prior to registration.
    • Patients must have Zubrod Performance Status ≤ 2.
    • Patients must have evidence of adequate renal function, as defined by:
      • creatinine clearance (CrCl) ≥ 30 mL/min., as measured by a 24-hour urine collection, or estimated by the Cockcroft and Gault formula; or
      • serum creatinine < 2.5 mg/dL. Values must be obtained within 28 days prior to registration. Estimated creatinine clearance = (140
        •age) x wt (kg) x 0.85 (if female) 72 x creatinine (mg/dl).
    • Patients must have adequate hepatic function defined by the following within 42 days prior to registration:
      • Total bilirubin ≤ 1.5 x IULN (institutional upper limit of the norm); AND
      • AST and ALT ≤ 3.0 x IULN o. Patients must not have chronic obstructive pulmonary disease with a forced expiratory volume in 1 second (FEV1) < 50% of predicted normal. FEV1 is required for patients suspected of having chronic obstructive pulmonary disease and are not eligible if FEV1 is < 50% of predicted normal. p. Patients must not have moderate or severe persistent asthma within the past 2 years and must not have currently uncontrolled asthma of any classification.
    • Patients must meet one of the following criteria:
      • Be acceptable for transplant per institutional guidelines and the criteria evidencing this must be documented on the S1803 Onstudy Form; OR
      • Note that these are guidelines and not required criteria.)
      • Have completed autologous stem cell transplant within 180 days prior to registration.
    • Patients must not have had prior autograft or allograft, or prior organ transplant requiring immunosuppressive therapy.
    • Patient’s with human immunodeficiency virus (HIV) are eligible providing they are on effective antiretroviral therapy and have undetectable viral load at their most previous viral load test and within 6 months prior to registration.
    • Patients must not have known allergy to any of the study drugs.
    • Patients with uncontrolled bacterial, viral or fungal infections (currently taking medication and with progression or no clinical improvement) at time of enrollment are not eligible.
    • Patients must not have known central nervous system (CNS) involvement with multiple myeloma, defined as CSF positivity for plasma cells at any time or a parenchymal CNS plasmacytoma at time of enrollment. Lumbar puncture is not required.
    • Patients must not be seropositive for hepatitis C (except in the setting of sustained virologic response, defined as undetectable viral load at least 12 weeks after completion of antiviral therapy). HCV testing is only required if clinically indicated or if the patient has a history of HCV.
    • Patients must be able to take and swallow oral medication (capsules) whole. Patients may not have any known impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of study drug (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
    • No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for three years. 
    • Patients must not have any uncontrolled intercurrent illness including (not limited to):
      • Symptomatic CHF (NYHA III/IV), unstable angina pectoris or coronary angioplasty, or stenting within 6 months prior to registration, Unstable cardiac arrhythmia (ongoing cardiac dysrhythmias of NCI CTCAE v5.0 Grade ≥ 2), intracardiac defibrillators, known cardiac metastases, or abnormal cardiac valve morphology (≥ Grade 3), or known psychiatric illness that would limit study compliance.
    • For patients who have not yet received transplant:
      • Patients must be willing and able to return to the transplant center for their assigned treatment after randomization. Note that patients need not have a direct relationship with the transplant center in order to register.
    • Patients must submit specimens for MRD.  Note that patients are not ineligible based solely on archival specimens being unavailable.
    • Patients must be offered participation in specimen banking for future research. 
    • Patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines.
    • As a part of the OPEN registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system.


    Exclusion Criteria:

    • Patients with smoldering myeloma are not eligible. Patients with purely non-secretory MM as measured by electrophoresis and immunofixation and the absence of Bence Jones proteins in the urine are not eligible. Patients must have measurable M protein in the serum (defined as ≥ 0.5g/dL) or urine (defined as ≥ 200 mg/24h). Patients with plasma cell leukemia are not eligible.
    • Patients must not have any organ involvement by amyloidosis or evidence of amyloidosis related organ dysfunction.
    • Patients must not have progressive disease at any time prior to registration.
    • Patients must not be refractory to either lenalidomide or daratumumab/rHuPH20.
    • Patients must not be intolerant to either lenalidomide or daratumumab/rHuPH20.
    • Patients must not have received any investigational agents within 14 days prior to registration.
    • Patients must not have chronic obstructive pulmonary disease with a forced expiratory volume in 1 second (FEV1) < 50% of predicted normal. FEV1 is required for patients suspected of having chronic obstructive pulmonary disease and are not eligible if FEV1 is < 50% of predicted normal.
    • Patients must not have moderate or severe persistent asthma within the past 2 years and must not have currently uncontrolled asthma of any classification.
    • Patients must not have had prior autograft or allograft, or prior organ transplant requiring immunosuppressive therapy.
    • Patients must not have known allergy to any of the study drugs.
    • Patients with uncontrolled bacterial, viral or fungal infections (currently taking medication and with progression or no clinical improvement) at time of enrollment are not eligible.
    • Patients must not have known central nervous system (CNS) involvement with multiple myeloma, defined as CSF positivity for plasma cells at any time or a parenchymal CNS plasmacytoma at time of enrollment. Lumbar puncture is not required.
    • Patients must not be seropositive for hepatitis C (except in the setting of sustained virologic response, defined as undetectable viral load at least 12 weeks after completion of antiviral therapy). HCV testing is only required if clinically indicated or if the patient has a history of HCV.
    • No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for three years.
    • Patients must not have any uncontrolled intercurrent illness including (not limited to): Symptomatic CHF (NYHA III/IV), unstable angina pectoris or coronary angioplasty, or stenting within 6 months prior to registration, Unstable cardiac arrhythmia (ongoing cardiac dysrhythmias of NCI CTCAE v5.0 Grade ≥ 2), intra-cardiac defibrillators, known cardiac metastases, or abnormal cardiac valve morphology (≥ Grade 3), or known psychiatric illness that would limit study compliance.

    Registration Step 2 - First Randomization (Post-ASCT, Pre-Maintenance)

    Inclusion Criteria:

    • Patients must have completed ASCT within 180 days prior to registering to Step 2.
    • Patients must not have received any other maintenance therapy post-ASCT and prior to Step 2 registration.
    • Patients must not have had progressive disease between induction and registration to Registration Step 2.
    • Patients must have one of the following performed within 60 days prior to registration for disease assessment: diagnostic quality skeletal survey, whole body CT scan, MRI, or PET.
    • Patients must have Zubrod Performance Status ≤ 2 f. Patients must have adequate bone marrow function as evidenced by platelets ≥ 75,000/mm^3 and ANC ≥ 1,000/mm^3 within 28 days prior to first randomization:
    • Patients must have adequate hepatic function defined by the following within 28 days prior to first randomization:
      • Total bilirubin ≤ 1.5 x IULN (institutional upper limit of the norm) AND 2. AST and ALT ≤ 3.0 x IULN.
    • Patients must have evidence of adequate renal function, as defined by creatinine clearance (CrCl) ≥ 30 mL/min., as measured by a 24-hour urine collection, or estimated by the Cockcroft and Gault formula, or have a serum creatinine < 2.5 mg/dL within 28 days prior to first randomization. Estimated creatinine clearance = (140
      •age) x wt (kg) x 0.85 (if female) 72 x creatinine (mg/dl).
    • All ASCT-related toxicities must have recovered to ≤ Grade 1 (except for alopecia, fatigue and amenorrhea) prior to first randomization. 
    • Mucositis and gastrointestinal symptoms must have resolved to ≤ Grade 1.
    • Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10-14 days prior to registration. FCBP must agree to have a second pregnancy test within 24 hours prior to starting Cycle 1. Further, FCBP must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control: one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before starting lenalidomide. FCBP must also agree to ongoing pregnancy testing and must agree to not become pregnant for at least 3 months after the last dose of study treatment. A FCBP is a female who:
      • has achieved menarche (first menstrual cycle) at some point;
      • has not undergone a hysterectomy (the surgical removal of the uterus) or bilateral oophorectomy (the surgical removal of both ovaries); or
      • has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time during the preceding 24 consecutive months). Men must agree to use a latex condom during sexual contact with a FCBP, even if they have had a successful vasectomy, during the study treatment and for 3 months after the last dose of study treatment.
    • Patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines.


    Exclusion Criteria:

    • Patients must not have received any other maintenance therapy post-ASCT and prior to Step 2 registration.
    • Patients must not have had progressive disease between induction and registration to Registration Step 2.

    Registration Step 3
    •Second Randomization (Post 24 Months Maintenance)

      Inclusion Criteria:

      • Patients must have completed 24 cycles of protocol maintenance with either lenalidomide or lenalidomide + daratumumab/rHuPH20.
      • Patients must have 24-month MRD by NGS test results available and must be MRD negative. Patients whose PCR results are indeterminable will be considered to have positive results.
      • Patients must be in very good partial remission (VGPR) or better by IMWG response criteria.
      Biologic/Vaccine, Drug
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      Mayo Clinic — Rochester, MN

      NRG-BR004, A Randomized, Double-Blind, Phase III Trial of Taxane/Trastuzumab/Pertuzumab with Atezolizumab or Placebo in First-Line HER2-Positive Metastatic Breast Cancer

      A Study of Taxane, Trastuzumab, and Pertuzumab With or Without Atezolizumab in Treating Metastatic Breast Cancer Patients

      Ciara O'Sullivan
      All
      18 years and over
      Phase 3
      This study is NOT accepting healthy volunteers
      0000-101062-P01-RST
      19-006737
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      Inclusion Criteria:
       

      • Adults, 18 years or older.
      • The patient must have signed and dated an Institutional Review Board (IRB)-approved consent form that conforms to federal and institutional guidelines.
      • Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
      • Histologically confirmed adenocarcinoma of the breast with locally recurrent, unresectable disease or metastatic disease confirmed as described below; eligible patients include those with either: 
        • De novo metastatic disease presenting without prior history of HER2-positive breast cancer: 
          • Diagnosis should have been made from a biopsy of a metastatic disease site, but biopsy from the breast primary or involved regional lymph nodes is acceptable if biopsy of the metastatic sites was thought to carry excessive risk for the patient.
        • Locally recurrent or metastatic disease following prior therapy for early breast cancer: Diagnosis must have been made from the biopsy of the locally recurrent or metastatic disease.
        • There must be an interval of ≥ 6 months between completion of neoadjuvant/adjuvant HER2-targeted therapy and documentation of locally recurrent or metastatic HER2-positive disease by biopsy.
      • Patients must have measurable disease based on RECIST 1.1, as determined by the site, to be eligible.
      • The tumor specimen obtained at the time of diagnosis of locally recurrent or metastatic disease must have been determined to be HER2-positive based on central testing according to American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines (Wolff 2018); HER2 status will initially be assessed using a Food and Drug Administration (FDA)-cleared IHC assay; positive is defined as IHC 3+ staining intensity; if HER2 IHC results are equivocal (2+), then HER2 status will be determined using a FDA-cleared HER2 in situ hybridization (ISH) test according to ASCO/CAP guidelines; sites can send biopsy specimens for central testing which have been determined to be HER2-positive or initially equivocal by either IHC or ISH on local testing.
      • The tumor specimen obtained at the time of diagnosis used for HER2 testing must also have central testing for PD-L1 status; patients will be eligible irrespective of PD-L1 testing result including PD-L1 indeterminant.
      • The tumor specimen obtained at the time of diagnosis used for HER2 and PD-L1 testing should also have central testing for estrogen receptor (ER) and progesterone receptor (PgR) according to current ASCO/CAP guideline recommendations for hormone receptor testing; patients with 1% ER and PgR staining by IHC will be classified as negative; if sufficient material for central confirmation of ER and PgR is unavailable, local testing results for ER and PgR may be used for eligibility.
      • Localized palliative radiation therapy is allowed for symptom management if completed ≥ 14 days prior to randomization.
      • Patients must have imaging of the chest/abdomen/pelvis, preferably with a computed tomography (CT) scan, and a bone scan within 4 weeks prior to randomization; (NOTE: if a patient is unable to receive CT contrast, a magnetic resonance imaging [MRI] of the abdomen/pelvis and non-contrast chest CT should be performed; positron emission tomography/computed tomography [PET/CT] is not an acceptable alternative).
      • MRI of the brain (or contrast CT scan of the brain if patients are unable to undergo MRI) must be obtained in patients with symptoms suggesting possible central nervous system (CNS) metastatic disease; neuroimaging is recommended but not required in asymptomatic patients.
      • Absolute neutrophil count (ANC) must be ≥ 1200/mm^3 (within 14 days prior to randomization).
      • Platelet count must be ≥ 100,000/mm^3 (within 14 days prior to randomization).
      • Hemoglobin must be ≥ 8 g/dL (within 14 days prior to randomization).
      • Total bilirubin must be ≤ 1.5 x upper limit of normal (ULN) for the lab or direct bilirubin ≤ ULN for patients with bilirubin levels > 1.5 x ULN (within 14 days prior to randomization).
      • Aspartate aminotransferase (AST) and alanine aminotransaminase (ALT) must be ≤ 2.5 x ULN for the lab or ≤ 5 x ULN for patients with liver metastases (within 14 days prior to randomization).
      • Serum creatinine ≤ 1.5 x ULN or measured or calculated creatinine clearance ≥ 50 mL/min using the Cockroft-Gault formula for patients with creatinine levels > 1.5 x ULN for the lab (within 14 days prior to randomization).
      • Patients not receiving anti-coagulant therapy must have prothrombin time (PT) and international normalized ratio (INR) ≤ 1.5 x ULN within 14 days prior to randomization; for laboratories that do not report an ULN for the INR assay, use ≤ 1.5 as the value for the ULN; patients receiving anti-coagulants should have a baseline INR assessed, but the value does not affect eligibility.
      • A serum thyroid-stimulating hormone (TSH), free T4, and AM (morning) cortisol must be obtained within 14 days prior to randomization to obtain a baseline value and be within normal limits for the local laboratory.
      • Left ventricular ejection fraction (LVEF) assessment must be performed within 6 weeks prior to randomization; (LVEF assessment performed by echocardiogram is preferred; however, multigated acquisition scan (MUGA) scan may be substituted based on institutional preferences); the LVEF must be ≥ 55% regardless of the cardiac imaging facility's lower limit of normal.
      • Administration of atezolizumab may have an adverse effect on pregnancy and poses a risk to the human fetus, including embryo-lethality; women of child-bearing potential and men must agree to use adequate contraception (non-hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 5 months (150 days) after the last dose of atezolizumab/placebo and 7 months after the last dose of trastuzumab and pertuzumab; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.


      Exclusion Criteria:
       

      • Patients with known primary central nervous system (CNS) malignancy or symptomatic CNS metastases are excluded, with the following exceptions: 
        • Patients with asymptomatic untreated CNS disease may be enrolled, provided all of the following criteria are met: 
          • Evaluable or measurable disease outside the CNS;
          • No metastases to brain stem, midbrain, pons, medulla, cerebellum, or within 10 mm of the optic apparatus (optic nerves and chiasm);
          • No history of intracranial hemorrhage or spinal cord hemorrhage;
          • No ongoing requirement for dexamethasone for CNS disease; patients on a stable dose of anticonvulsants are permitted;
          • No neurosurgical resection or brain biopsy within 28 days prior to randomization.
        • Patients with asymptomatic treated CNS metastases may be enrolled, provided all the criteria listed above are met as well as the following: 
          • Radiographic demonstration of improvement upon the completion of CNS directed therapy and no evidence of interim progression between the completion of CNS directed therapy and the screening radiographic study;
          • No stereotactic radiation or whole-brain radiation within 4 weeks prior to randomization;
          • Screening CNS radiographic study 4 weeks from completion of radiotherapy and 2 weeks from discontinuation of corticosteroids.
      • Known leptomeningeal carcinomatosis.
      • Patients with metastatic disease limited to the CNS.
      • History of systemic anti-cancer therapy (e.g., chemotherapy, targeted therapy) for metastatic breast cancer (MBC) with the exception of administration of trastuzumab or lapatinib concurrently with radiation therapy for brain metastases; toxicities related to lapatinib should be ≤ grade 1, per the CTCAE version (v)5.0 and must have been completed at least 2 weeks prior to randomization.
      • History of exposure to cumulative doses of doxorubicin greater than 360 mg per square meter of body-surface area or its equivalent.
      • Prior treatment with mTOR inhibitors or CDK 4/6 inhibitors in combination with endocrine therapy for treatment of metastatic disease.
      • Prior treatment with CD137 agonists or immune checkpoint-blockade therapies, including anti-CD40, anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies.
      • History of non-breast malignancies (except for in situ cancers treated only by local excision and basal cell and squamous cell carcinomas of the skin) within 5 years prior to randomization.
      • Uncontrolled hypertension defined as sustained systolic blood pressure (BP) > 150 mmHg or diastolic BP > 90 mmHg; (patients with initial BP elevations are eligible if initiation or adjustment of BP medication lowers pressure to meet entry criteria).
      • History of asymptomatic LVEF decline to < 40% during or after prior HER2-targeted therapy.
      • Cardiac disease (history of and/or active disease) that would preclude the use of the drugs included in the treatment regimens; this includes but is not confined to: 
        • Active cardiac disease;
        • Angina pectoris that requires the current use of anti-anginal medication;
        • Ventricular arrhythmias except for benign premature ventricular contractions; 
        • Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication; 
        • Conduction abnormality requiring a pacemaker; 
        • Valvular disease with documented compromise in cardiac function; or 
        • Symptomatic pericarditis.
      • History of cardiac disease:
        • Prior myocardial infarction documented by elevated cardiac enzymes or persistent regional wall abnormalities on assessment of left ventricular (LV) function; 
        • History of documented congestive heart failure (CHF) defined as symptomatic heart failure with an LVEF < 40%; or 
        • Documented cardiomyopathy.
      • Nervous system disorder (paresthesia, peripheral motor neuropathy, or peripheral sensory neuropathy) ≥ grade 2, per the Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0. 
      • History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins. 
      • Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells or other recombinant antibodies.
      • Known allergy or hypersensitivity to the components of the atezolizumab formulation or to any of the study drugs or excipients, (e.g., Cremophor EL).
      • History or risk of autoimmune disease, including, but not limited to, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjogren's syndrome, Bell's palsy, Guillain-Barre syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis: 
        • Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone may be eligible;
        • Patients with controlled type 1 diabetes mellitus on a stable insulin regimen may be eligible;
        • Patients with eczema, psoriasis, lichen simplex chronicus of vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided that they meet the following conditions: 
          • Patients with psoriasis must have a baseline ophthalmologic exam to rule out ocular manifestations;
          • Rash must cover less than 10% of body surface area (BSA);
          • Disease is well controlled at baseline and only requiring low-potency topical steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%, flucinolone 0.01%, desonide 0.05%, aclometasone dipropionate 0.05%); 
          • No acute exacerbations of underlying conditions within the last 12 months (not requiring psoralen plus ultraviolet A radiation [PUVA], methotrexate, retinoids, biologic agents, oral calcineurin inhibitors; high potency or oral steroids).
      • Treatment with systemic immunosuppressive medications (including but not limited to interferons, IL-2) within 4 weeks or 5 half-lives of the drug, whichever is longer, prior to randomization 
      • Treatment with systemic immunosuppressive medications (including but not limited to prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti−tumor necrosis [anti-TNF] factor agents) within 14 days prior to randomization or anticipation of need for systemic immunosuppressive medications during the study.
        • Note: Intranasal and inhaled corticosteroids or systemic corticosteroids at doses that do not exceed 10 mg/day of prednisone or an equivalent corticosteroid are allowed.
      • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 2 weeks prior to randomization. 
      • Active hepatitis B virus (HBV) infection, defined as having a positive hepatitis B surface antigen (HBsAg) test at screening; patients with a past or resolved HBV infection, defined as having a negative HBsAg test and a positive total hepatitis B core antibody (HBcAb) test at screening, are eligible for the study if active HBV infection is ruled out on the basis of HBV deoxyribonucleic acid (DNA) viral load per local guidelines
        •Active hepatitis C virus (HCV) infection, defined as having a positive HCV antibody test at screening confirmed by a polymerase chain reaction (PCR) positive for HCV ribonucleic acid (RNA).
      • Patients with clinically active tuberculosis. 
      • Patients known to be human immunodeficiency virus (HIV) positive are eligible if they meet the following criteria within 4 weeks prior to randomization:
        • A stable regimen of highly active anti-retroviral therapy (HAART); and
        • No requirement for concurrent antibiotics or antifungal agents for the prevention of opportunistic infections; and
        • A CD4 count above 250 cells/mcL and an undetectable HIV viral load on standard PCR-based tests.
      • Severe infection within 4 weeks prior to randomization, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia. 
      • Prior allogeneic stem cell or solid organ transplantation.
      • Symptomatic peripheral ischemia. 
      • History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis or ≥ grade 1 pulmonary fibrosis, per the CTCAE v5.0, on screening chest CT scan.
      • Administration of a live, attenuated vaccine within 4 weeks prior to randomization or anticipation that such vaccine will be required during the study:
        • Patients must agree not to receive live, attenuated influenza vaccine (e.g., FluMist) within 4 weeks prior to randomization, during treatment or within 5 months following the last dose of atezolizumab/placebo. 
      • Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease.
      Biologic/Vaccine, Drug, Other, Administration of antineoplastic agent, Chemotherapy, Drug therapy, Immunotherapy for cancer
      Breast cancer, Cancer
      Atezolizumab, Biological therapy for cancer, Cancer treatment, Chemotherapy, Chemotherapy for breast cancer, Malignant tumor of breast, Medical Oncology, Metastatic human epidermal growth factor 2 positive carcinoma of breast, Trastuzumab, atezolizumab, paclitaxel, pertuzumab, trastuzumab
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      Mayo Clinic — Rochester, MN

      A Phase 2, Open-Label, Single-Arm, Multicenter Study to Evaluate the Efficacy and Safety of Pemigatinib in Participants With Previously Treated Locally Advanced/Metastatic or Surgically Unresectable Solid Tumor Malignancies Harboring Activating FGFR Mutations or Translocations (FIGHT-207) (FIGHT-207)

      A Study to Evaluate the Effectiveness and Safety of Pemigatinib in Previously-treated, Locally Advanced/Metastatic or Surgically Unresectable Solid Tumor Malignancies Harboring Activating FGFR Mutations or Translocations (FIGHT-207)

      Amit Mahipal
      All
      18 years and over
      Phase 2
      This study is NOT accepting healthy volunteers
      0000-101072-P01-RST
      19-008116
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      Inclusion Criteria:
       

      • Histologically or cytologically confirmed solid tumor malignancy that is advanced or metastatic or is surgically unresectable. 
      • Radiographically measurable disease (per RECIST v1.1 or RANO for primary brain tumors). Tumor lesions located in a previously irradiated area or in an area subjected to other loco-regional therapy are considered measureable if progression has been clearly demonstrated in the lesion. 
      • Documentation of an FGFR1-3 gene mutation or translocation. 
      • Objective progression after at least 1 prior therapy and no therapy available that is likely to provide clinical benefit. Participants who are intolerant to or decline the approved therapy are eligible only if they have no therapy available that is likely to provide clinical benefit. 
      • Eastern Cooperative Oncology Group performance status 0 to 2.
      • Baseline archival tumor specimen (if < 12 months from date of screening) or willingness to undergo a pretreatment tumor biopsy to obtain the specimen. Must be a tumor block or approximately 15 unstained slides from biopsy or resection of primary tumor or metastasis. 
      • Willingness to avoid pregnancy or fathering children.


      Exclusion Criteria:
       

      • Prior receipt of a selective FGFR inhibitor in the past 6 months. 
      • Receipt of anticancer medications or investigational drugs for any indication or reason within 28 days before first dose of pemigatinib. 
      • Cannot be a candidate for potentially curative surgery. 
      • Current evidence of clinically significant corneal or retinal disorder as confirmed by ophthalmologic examination. 
      • Radiation therapy administered within 2 weeks of enrollment/first dose of study treatment.
      • Untreated brain or central nervous system (CNS) metastases or brain or CNS metastases that have progressed (e.g., evidence of new or enlarging brain metastasis or new neurological symptoms attributable to brain or CNS metastases). 
      • Known additional malignancy that is progressing or requires active treatment. 
      • History of calcium and phosphate hemostasis disorder or systemic mineral imbalance with ectopic calcification of soft tissues.
      • Clinically significant or uncontrolled cardiac disease. 
      • Active chronic or current infectious disease requiring systemic antibiotic, antifungal, or antiviral treatment within 2 weeks before enrollment (participants with asymptomatic chronic infections on prophylactic treatment are allowed). 
      • Evidence of active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection (defined as elevated transaminases or cirrhosis; chronic HBV/HCV infection with no cirrhosis and no elevated transaminases is allowed). 
      • Known HIV infection. 
      • Use of any potent CYP3A4 inhibitors or inducers or moderate CYP3A4 inducers within 14 days or five half-lives (whichever is longer) before the first dose of study drug/treatment. 
      • Women who are pregnant or breastfeeding.
      Drug, Administration of antineoplastic agent, Drug therapy
      Brain tumor, Cancer, Tumors and masses
      Cancer treatment, Carrier of chromosome translocation, Genetic mutation, Intracranial tumor, Malignant neoplastic disease, Medical Oncology, Nervous system, Pemigatinib, Secondary malignant neoplastic disease, Solid tumor configuration, Tumor surgically unresectable, pemigatinib
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      Mayo Clinic — Rochester, MN

      TED16132, An Open-label, First-in-human, Single Agent, Dose-escalation and Expansion Study for the Evaluation of Safety, Pharmacokinetics, Pharmacodynamics and Anti-tumor Activity of SAR442085 in Patients With Relapsed or Refractory Multiple Myeloma (RRMM)

      A Study of SAR442085 in Relapsed or Refractory Multiple Myeloma

      Prashant Kapoor
      All
      18 years and over
      Phase 1
      This study is NOT accepting healthy volunteers
      0000-101086-P01-RST
      19-008701
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      Inclusion Criteria:
       

      • Participant must be at least 18 years of age or of the country's legal age of majority if the legal age is >18 years old at the time of signing the informed consent. 
      • Participant has given voluntary written informed consent. 
      • Participant has been previousy diagnosed with multiple myeloma based on standard criteria. 
      • Part A:
        • Participant has received at least 3 prior lines of therapy for multiple myeloma, or at least 2 prior lines of therapy if at least 1 of those lines consisted of 2 or more multi-agent regimens (eg, multi-agent induction regimen with autologous stem cell transplantation, followed by maintenance regimen). 
        • Prior therapy for multiple myeloma has included at least 1 proteasome inhibitor (bortezomib, carfilzomib, ixazomib), at least 1 immunomodulatory agent (lenalidomide, thalidomide, pomalidomide), at least 1 anti-CD38 monoclonal antibody and at least 1 steroid. 
        • Participant had at least a minimal response (MR) to the anti-CD38 antibody containing regimen and had last dose of anti-CD38 monoclonal antibody at least 9 months prior to study entry, except the last cohort(s) of Part A who are anti CD38 naïve. 
      • Part B and the last cohort(s) of Part A:
        • Participant has received at least 3 prior lines of therapy for multiple myeloma, or at least 2 prior line of therapy if at least 1 of those lines consisted of 2 or more multi-agent regimens (eg, multi-agent induction regimen with autologous stem cell transplantation, followed by maintenance regimen).
        • Prior therapy for multiple myeloma has included at least 1 proteasome inhibitor (bortezomib, carfilzomib, ixazomib), at least 1 immunomodulatory agent (lenalidomide, thalidomide, pomalidomide) and at least 1 steroid.
        • Prior therapy has not included an anti-CD38 monoclonal antibody. 
      • Participant has myeloma disease progression on or after last therapy. 
      • Participant must have measurable disease as defined as at least one of the following: 
        • Serum M protein ≥0.5 g/dL (≥5 g/L);
        • Urine M protein ≥200 mg/24 hours;
        • Serum FLC assay: Involved FLC assay ≥10 mg/dL (≥100 mg/L) and an abnormal serum;
        • FLC ratio (<0.26 or >1.65). 
      • A male participant must agree to use contraception during the intervention period and for at least 150 days after the last dose of study drug and refrain from donating sperm during this period.
      • A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: 
        • Not a woman of childbearing potential (WOCBP);
        • A WOCBP who agrees to follow the contraceptive guidance during the intervention period and for at least 150 days after the last dose of study intervention.


      Exclusion Criteria:
       

      • Participant is diagnosed or treated for another malignancy within 3 years prior to enrollment, with the exception of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, superficial bladder carcinoma or low risk prostate cancer. 
      • Participant has an Eastern Cooperative Oncology Group (ECOG) performance status score > 2.
      • Participant has a history of Chronic obstructive pulmonary disease (COPD) or asthma. 
      • Participant has not recovered from adverse reactions to prior myeloma treatment or procedures (chemotherapy, immunotherapy, radiation therapy) to NCI CTCAE Grade ≤1 or baseline (exception: alopecia).
      • Participant has congestive heart failure (New York Heart Association) Grade ≥ II; cardiac myopathy, active ischemia, or any other uncontrolled cardiac condition such as angina pectoris, clinically significant arrhythmia requiring therapy including anticoagulants, or clinically significant uncontrolled hypertension, QT interval corrected by the Fridericia method > 480 msec (Grade ≥ 2). 
      • Participant has had acute myocardial infarction within 6 months before first dose of study medication. 
      • Participant has ongoing sensory or motor neuropathy of National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Grade ≥ 3. 
      • Participant has active autoimmune disease including autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura, inflammatory bowel syndrome, pneumonitis or any chronic condition requiring a higher corticosteroid systemic equivalent than prednisone 10 mg daily.
      • Known acquired immunodeficiency syndrome (AIDS) or related illnesses or human immunodeficiency virus (HIV) disease requiring antiretroviral treatment, or to have active hepatitis A, B (defined as a known positive hepatitis B surface antigen (HBsAg) result or positive HepB DNA), or C (defined as a known quantitative hepatitis C [HCV] ribonucleic acid RNA results greater than the lower limits of detection of the assay or positive HCV antigen) infection.
      • Participant has positive Coombs test at baseline. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
      Drug, Administration of antineoplastic agent, Drug therapy
      Cancer, Multiple myeloma, Plasma cell disorders
      Cancer treatment, Hematopoietic system, Immune system, Medical Oncology, Relapse multiple myeloma, Targeted drug therapy
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      MK-1026-001 A Phase 1/2 Dose Escalation Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of MK-1026 in Selected Subjects with Relapsed or Refractory Hematologic Malignancies

      A Study of MK-1026 in Patients with Selected Hematologic Malignancies

      Sameer Parikh
      All
      18 years and over
      Phase 1/2
      This study is NOT accepting healthy volunteers
      0000-101099-P01-RST
      19-010567
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      Inclusion Criteria:

      • Signed written informed consent granted prior to initiation of any study-specific procedures. 
      • 18 years of age and older.
      • For the dose escalation cohorts, relapsed or refractory subjects with a diagnosis of B-cell NHL, CLL/SLL and WM who have received at least two prior systemic therapies . Subjects must have failed or are intolerant to standard therapies and cannot be a candidate for standard salvage regimens. Subjects with low grade lymphoma must be progressing and requiring treatment.. 
      • For the expansion cohorts, the following criteria must be met:
        • Cohort A: Relapsed/Refractory (R/R) CLL/SLL subjects with at least 2 prior systemic therapies and previously treated with a covalent BTKi who must have a documented BTK mutation on C481 residue;
        • Cohort B: R/R CLL/SLL subjects who have failed or were intolerant to a BTKi with documentation of the absence of BTK mutation on C481 residue. In this study, intolerance to standard therapy is defined as having experienced a grade 3 or higher adverse event that was caused by the standard therapy and resulted in treatment discontinuation;
        • Cohort C: Richter's transformation subjects who have failed at least one prior therapy;
        • Cohort D: Follicular Lymphoma (FL) subjects who have failed at least 2 prior systemic therapies and are histology grade 1, 2, or 3A;
        • Cohort E: Mantle Cell Lymphoma (MCL) subjects who have failed at least 2 prior systemic therapies;
        • Cohort F: Marginal Zone Lymphoma (MZL) subjects who have failed at least 2 prior systemic therapies;
        • Cohort G: High-grade B-cell lymphoma subjects who have failed at least 2 prior systemic therapies and have known MYC and BCL2 and/or BCL6 translocations;
        • Cohort H: Waldenström macroglobulinemia (WM) subjects who have failed at least 2 prior systemic therapies.
      • Disease status requirement: 
        • For CLL subjects, symptomatic disease that mandates treatment (Hallek et al. 2018); 
        • For B-cell NHL subjects, measurable disease by imaging scan;
        • For WM, serum immunoglobulin M (IgM) with a minimum IgM level of ≥ 2 times the upper limit of normal (ULN). 
      • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. 
      • Good organ function:
        • Creatinine clearance of ≥ 60 mL/min as estimated by the Cockcroft-Gault equation or by 24-hour urine collection;
        • Total bilirubin ≤ 1.5 x institutional ULN (total bilirubin of ≤ 3 x institutional ULN in subjects with documented Gilbert's syndrome);
        • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × institutional ULN;
        • Platelet count ≥ 50,000/µL;
        • Absolute neutrophil count (ANC) ≥ 1000/µL;
        • Hemoglobin (Hgb) ≥ 8.0 g/dL, stable for ≥ 1 week.
      • For men and women of child-bearing potential, willing to use adequate contraception (e.g., latex condom, cervical cap, diaphragm, abstinence, etc.) for the entire duration of the study.
      • Female subjects of child-bearing potential must have a negative serum pregnancy test within 14 days of the first day of drug dosing.
      • Ability to swallow oral medications without difficulty.


      Exclusion Criteria:

      • Had immunotherapy, radiotherapy, radioimmunotherapy, biological therapy, chemotherapy, or treatment with an investigational product within 5 half-lives or four weeks (whichever is shorter) prior to treatment initiation, or oral therapy within 5 half-lives or one week (whichever is shorter) prior to treatment initiation. 
      • Transformation of FL to a more aggressive subtype of lymphoma or grade 3b FL.
      • Subjects currently being treated with the following drugs:
        • CYP 2C9 substrates with a narrow therapeutic index (such as warfarin, phenytoin);
        • CYP 2C8 substrates with a narrow therapeutic index (such as paclitaxel);
        • CYP 2C19 substrates with a narrow therapeutic index (such as S-mephenytoin);
        • CYP 2D6 substrates with a narrow therapeutic index (such as thioridazine, pimozide);
        • P-gp substrates with a narrow therapeutic index (such as digoxin)
          • Note: A washout period of at least 5 times the half-life after the last dose of any of the above treatments is required for a subject to be eligible for study enrollment. 
      • Prior allogeneic bone marrow transplant. 
      • Active central nervous system (CNS) involvement. 
      • Pregnant or breast-feeding women. 
      • Has significant, ongoing co-morbid conditions which would preclude safe delivery of the study drug. 
      • Uncontrolled illness including but not limited to ongoing or active infection, symptomatic congestive heart failure (New York Heart Association [NYHA] Class III or IV heart failure), unstable angina pectoris, cardiac arrhythmia, cardiac infarction in the past six months, and psychiatric illness that would limit compliance with study requirements. 
      • QTc prolongation (defined as a QTc > 450 msecs) or other significant electrocardiogram (ECG) abnormalities including 2nd degree atrioventricular (AV) block type II, 3rd degree AV block, or bradycardia (ventricular rate less than 50 beats/min). If the screening ECG has a QTc > 450 msecs, the ECG can be submitted for a centralized, cardiologic evaluation. 
      • Active human immunodeficiency virus (HIV) infection, Hepatitis B, or Hepatitis C infection. 
      • Other medical or psychiatric illness or organ dysfunction which, in the opinion of the Investigator, would either compromise the subject's safety or interfere with the evaluation of the safety of the study agent.
      • History of prior cancer within < 1 year, except for basal cell or squamous cell carcinoma of the skin, cervical cancer in situ or other in situ carcinomas.
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      A Phase I/II Study of MCLA-128, a Full Length IgG1 Bispecific Antibody Targeting HER2 and HER3, in Patients With Solid Tumors (eNRGy)

      A Study of MCLA-128 in Patients with Solid Tumors Harboring an NRG1 Fusion

      Wen Wee Ma
      All
      18 years and over
      Phase 2
      This study is NOT accepting healthy volunteers
      0000-101101-P01-RST
      19-007454
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      Inclusion Criteria:

      • Age 18 years or older;
      • At least one measurable lesion according to RECIST v1.1 OR evaluable disease for a limited number of patients (up to 10) in Group H.
      • Performance status of ECOG 0, 1 or 2.
      • Estimated life expectancy of at least 12 weeks;
      • Toxicities incurred as a result of previous anti-cancer therapy resolved to ≤ Grade 1 (as defined by NCI CTCAE v4.03) except for alopecia, Grade 2 sensory neurotoxicity, or any other toxicity that in the opinion of the Investigator does not affect the assessment of adverse events related to the study drug.
      • Treatment with anti-cancer medication or investigational drugs within the following intervals before the first dose of MCLA-128:
        • > 14 days or > 5 half-lives prior to study entry, whichever is shorter;
        • > 14 days for radiotherapy.
        • Note: A less than 1-week wash-out period is permitted only for palliative radiation to non-CNS disease with Sponsor approval.
      • Patient has recovered from prior surgery or other procedure or complication to ≤ Grade 2 or to baseline condition that in opinion of the Investigator does not affect the assessment of adverse events related to the study drug;
      • Laboratory values at Screening:
        • Absolute neutrophil count ≥ 1.5 x 10^9 /L without colony stimulating factor support for at least 7 days prior to Screening;
        • Platelets ≥ 100 x 10^9 /L without transfusion support for at least 7 days prior to Screening;
        • Hemoglobin ≥ 8 g/dL or ≥ 5 mmol/L;
        • Alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≤ 3 x upper limit of normal (ULN) and total bilirubin ≤ 1.5 x ULN; in cases of metastatic liver involvement, ALT/AST ≤ 5 x ULN and total bilirubin ≤ 2 x ULN will be allowed; in cases of antecedents of Gilbert’s syndrome when total bilirubin ≤ 3.0 x ULN or direct bilirubin ≤ 1.5 x ULN will be allowed;
        • Estimated glomerular filtration rate (GFR) of > 30 mL/min based on the Cockroft-Gault formula.
      • Able to provide at baseline a mandatory tumor biopsy sample (FFPE), preferably a block. If safe/feasible, a fresh FFPE biopsy sample is preferred; archival tissue is acceptable (preferably not more than 2 years old).
        • NOTE #1: For patients who received afatinib or other HER-targeting agents, a biopsy collected after the last line of treatment is strongly preferred to assess for mechanisms of acquired resistance.
        • NOTE #2: For patients with a locally confirmed NRG1 gene fusion, when archival tissue is not available and collection of a fresh biopsy is not safe or feasible during the screening period, these patients will be allowed to enroll in the MCLA128-CL01 trial provided they meet all other inclusion/exclusion criteria.
      • Negative pregnancy test results available as defined by a blood human chorionic gonadotropin (hCG) test during Screening and within 7 days of Cycle 1, Day 1 in women of childbearing potential (defined as women ≤50 years of age or history of amenorrhea for ≤12 months prior to study entry).
        • NOTE: Women with amenorrhea associated with prior treatment with antineoplastic medications are still considered as being of child-bearing potential.
      • Sexually active male and female patients of childbearing potential must agree to use one of the following highly effective methods of birth control during the entire duration of the study and for 6 months after final administration of MCLA-128:
        • combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:
          • oral;
          • intravaginal;
          • transdermal.
        • progestogen-only hormonal contraception associated with inhibition of ovulation 1:
          • oral;
          • injectable;
          • implantable.
        • intrauterine device (IUD);
        • intrauterine hormone-releasing system (IUS);
        • bilateral tubal occlusion;
        • vasectomized partner;*
        • sexual abstinence;**
        • Note that double barrier methods are not considered to be highly effective birth control methods.
        • * Note that sterility in female patients must be confirmed in the patients’ medical records and be defined as any of the following: surgical hysterectomy with bilateral oophorectomy, bilateral tubular ligation, natural menopause with last menses > 1 year ago; radiation induced oophorectomy with last menses > 1 year ago; chemotherapy induced menopause with 1-year interval since last menses; 1Note that a vasectomized partner is only a highly effective birth control method provided that partner is the sole sexual partner of the woman of childbearing potential trial participant and that the vasectomized partner has received medical assessment of the surgical success.
        • ** Note that sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the clinical trial and the preferred and usual lifestyle of the subject.
      • Ability to give written, informed consent prior to any study-specific Screening procedures, with the understanding that the consent may be withdrawn by the patient at any time without prejudice.
      • Capable of understanding the mandated and optional protocol requirements, is willing and able to comply with the study protocol procedures and has signed the main informed consent document. For any optional biopsy sampling (tissue and/or blood) and long-term sample storage, additional consent is required.
      • Patients must have received prior standard therapy appropriate for their tumor type and stage of disease, or in the opinion of the Investigator, would be unlikely to tolerate or derive clinically meaningful benefit from appropriate standard of care therapy or no satisfactory alternative treatment options are available.
      • Histologic or cytologic diagnosis of locally-advanced, unresectable or metastatic solid tumor malignancy with a documented NRG1 gene fusion, identified through molecular assays such as next generation sequencing-based assays [DNA or RNA], as routinely performed at CLIA or other similarly-certified laboratories. The following tumor types are included:
        • Group F: NSCLC;
        • Group G: pancreatic adenocarcinoma;
        • Group H: any other solid tumor.
        • NOTE: Patients harboring fusions that are predicted to be non-functional; i.e., lack of EGF-domain, will not be included in the study. For equivocal cases, including those with NRG1 as the upstream partner, the Sponsor will manually review genomic results and may request collateral testing, approve, or deny the case.


      Exclusion Criteria:

      • Pregnant or lactating.
      • Presence of an active uncontrolled infection or an unexplained fever greater than 38.5°C during Screening up to the first scheduled day of dosing. At the discretion of the Investigator, patients with tumor fever or a clinically insignificant minor infection may be enrolled (i.e., mild upper respiratory infection).
      • Known hypersensitivity to any of the components of MCLA-128 or history of severe hypersensitivity reactions to human or humanized monoclonal antibodies, including therapeutic antibodies.
      • Patients with the following infectious diseases are excluded:
        • known HIV;
        • active Hepatitis B infection (HBsAg positive) without receiving antiviral treatment
        • Note: Patients with active hepatitis B (HBsAg positive) must receive antiviral treatment with lamivudine, tenofovir, entecavir, or other antiviral agents, starting at least ≥ 7 days before the initiation of the study treatment; Patients with antecedents of Hepatitis B (anti-HBc positive, HBsAg and HBV-DNA negative) are eligible;
        • positive test for Hepatitis C ribonucleic acid (HCV RNA)
        • Note: Patients in whom HCV infection resolved spontaneously (positive HCV antibodies without detectable HCV-RNA) or those that achieved a sustained response after antiviral treatment and show absence of detectable HCV RNA ≥ 6 months (with the use of IFN-free regimens) or ≥ 12 months (with the use of IFN-based regimens) after cessation of antiviral treatment are eligible;
      • Known symptomatic or unstable brain metastases. Patients with asymptomatic brain metastases are eligible to participate if the metastases have been radiographically and clinically stable for at least one month. If on steroids for this indication, the patient must be on a stable dose for at least one month;
      • Patients with leptomeningeal metastases;
      • Previous or concurrent malignancy, excluding non-basal cell carcinoma of skin or carcinoma in situ of the uterine cervix unless the tumor was treated with curative or palliative intent and in the opinion of the Investigator, with Sponsor agreement, the previous or concurrent malignancy condition doesn’t affect the assessment of safety and efficacy of the study drug;
      • Presence of NYHA Class III or IV congestive heart failure or LVEF < 50% or history of significant cardiac disease, unstable angina, congestive heart failure, myocardial infarction, or ventricular arrhythmia requiring medication.
      • Presence of any other medical or psychological condition deemed by the Investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate or participate in the study, or interfere with the interpretation of the results.
      Drug, Administration of antineoplastic agent, Drug therapy
      Cancer, Tumors and masses
      Alteration of genetic material, Cancer treatment, Genetic mutation, Malignant neoplastic disease, Medical Oncology, Solid tumor configuration, Targeted drug therapy
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      MC1933 Development of Patient Derived Xenografts in Patients with Breast Cancer who have Residual Disease after Neoadjuvant Systemic Therapy (BEAUTY-3) (DPDXMST)

      A Study to Evaluate the Development of Patient Derived Xenografts in Patients With Breast Cancer

      Judy Boughey
      All
      18 years and over
      This study is NOT accepting healthy volunteers
      0000-101103-P01-RST
      19-009192
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      Inclusion Criteria:

      • Age ≥ 18 years.
      • Diagnosis of invasive breast cancer treated with neoadjuvant systemic therapy.
      • Surgically resectable disease following neoadjuvant systemic treatment.
      • At least one of the following must be true:
        • Received at least 2 weeks of neoadjuvant endocrine therapy;
        • Received at least 2 months of neoadjuvant chemotherapy with suggestion of residual disease on imaging;
        • Began neoadjuvant chemotherapy or endocrine therapy but discontinued due to evidence of progressive disease by MRI, US, or physical examination.
      • Provide written informed consent.
      • Willing to return to enrolling institution for breast cancer surgery.
      • Willingness to provide mandatory blood specimens for future research on breast cancer at Mayo Clinic.
      • Willingness to provide mandatory tissue specimens for future research on breast cancer at Mayo Clinic.
      • Willingness to provide mandatory tissue specimens for the generation of PDX and organoids to be used future research on breast cancer at Mayo Clinic.


      Exclusion Criteria:

      • Ineligible for surgery.
      • History of prior malignancy < 3 years prior to registration.
      • Exceptions for non-melanoma skin cancer, papillary thyroid cancer, non-invasive cancer (e.g., carcinoma in situ of the cervix).

      Eligibility last updated 7/25/23. Questions regarding updates should be directed to the study team contact.

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      TAS-120-201: A Phase 2 Study of TAS-120 in Metastatic Breast Cancers Harboring Fibroblast Growth Factor Receptor (FGFR) Amplifications

      A Study of TAS-120 in Patients With Metastatic Breast Cancer

      Karthik Giridhar
      All
      18 years and over
      Phase 2
      This study is NOT accepting healthy volunteers
      0000-101106-P01-RST
      19-010514
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      Inclusion Criteria:

      • Histologically or cytologically confirmed recurrent locally advanced or metastatic breast cancer not amenable to treatment with curative intent, meeting all of the criteria for 1 of the following cohorts:

      Cohort 1

      • HR+ HER2- breast cancer harboring an FGFR2 gene amplification. HR+ HER2- breast cancer is defined per the local pathology report as estrogen receptor (ER) >1% and/or progesterone receptor (PR) >1%, HER2-negative per American Society of Clinical Oncology (ASCO) and the College of American Pathologists (CAP) guidelines, 2018,
      • Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1,
      • Has received 1-3 prior endocrine-containing therapies and up to 2 prior chemotherapy regimens for advanced/metastatic disease;
      • Has received prior treatment with a CDK4/6 inhibitor or is ineligible for such: 
        • Treatment (per Investigator decision); 
        • Has experienced disease progression/recurrence within 1 month following the completion of any endocrine therapy for advanced/metastatic breast cancer.

      Cohort 2

      • TNBC harboring an FGFR2 gene amplification. TNBC is defined as negative for ER, PR and HER2. Negative for ER and PR includes the following:
        • Local pathology report classifies them as negative, Allred Score of 2 or below or <1% staining. HER2-negative per ASCO / CAP guidelines, 2018;
        • Measurable disease per RECIST 1.1;
        • Has received at least 1 prior chemotherapy or chemotherapy/immunotherapy;
        • (PD-L1/PD-1 inhibitors) regimen for advanced/metastatic disease;
        • Has experienced disease progression/recurrence during or after the most recent prior chemotherapy for advanced/metastatic breast cancer.

      Cohort 3

      • TNBC or HR+ HER2- breast cancer (defined as above) harboring an FGFR2 gene amplification.
      • Non measurable, evaluable disease per RECIST 1.1. Patients with bone-only disease must have lytic or mixed lytic-blastic lesions.
      • Other criteria for either HR+ HER2- breast cancer or TNBC should be met as described for Cohort 1 and 2, respectively.

      Cohort 4

      • HR+ HER2- breast cancer (defined as above) harboring an FGFR1 high-level gene amplification.
      • Measurable disease per RECIST 1.1.
      • Has received 1-2 prior endocrine-containing therapies and no more than 1 prior chemotherapy regimen for advanced/metastatic disease. Prior treatment with fulvestrant is not permitted.
      • Has received prior treatment with a CDK4/6 inhibitor or is ineligible for such: 
        • Treatment (per Investigator decision);
        • Pre/peri-menopausal patients must be on goserelin. Patients must have commenced treatment with goserelin or an alternative GnRH agonist at least 4 weeks prior to the first dose of fulvestrant. If patients have received an alternative GnRH agonist prior to study entry, they must switch to goserelin for the duration of the trial. Postmenopausal is defined as at least one of the following criteria: age ≥60 years; age <60 years and cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; and serum estradiol and follicle-stimulating hormone level within the laboratory's reference range for postmenopausal females; or documented bilateral oophorectomy;
        • Has experienced disease progression/recurrence within 1 month following the completion of any endocrine therapy for advanced/metastatic breast cancer.
      • Archival or (preferably) fresh tumor tissue must be available for central laboratory confirmation of FGFR amplification.
      • The patient has adequate organ function as defined by the following criteria:
        • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 × the upper limit of normal (ULN); if liver function abnormalities are due to underlying liver metastases, AST and ALT ≤ 5 × ULN;
        • Total bilirubin ≤ 1.5 × ULN or ≤ 3 × ULN in case of Gilbert's syndrome;
        • Absolute neutrophil count (ANC) ≥ 1.0 × 10^9/L without hematopoietic growth factor support;
        • Platelet count ≥ 75 × 10^9/L without transfusion support (that is, excluding measurements obtained within 3 days after transfusion of platelets);
        • Hemoglobin ≥ 9.0 g/dL without transfusion support (that is, excluding measurements within 7 days after transfusion of packed red blood cells or whole blood);
        • Serum phosphorus ≤ ULN;
        • Creatinine clearance (calculated or measured value): ≥ 40 mL/min.


      Exclusion Criteria:

      A patient must not meet any of the following exclusion criteria to be eligible for this study:

      • History and/or current evidence of any of the following disorders:
        • Non-tumor related alteration of the calcium-phosphorus homeostasis that is considered clinically significant in the opinion of the Investigator;
        • Ectopic mineralization/calcification, including but not limited to soft tissue, kidneys, intestine, or myocardia and lung, considered clinically significant in the opinion of the Investigator;
        • Retinal or corneal disorder confirmed by retinal/corneal examination and considered clinically significant in the opinion of the Investigator;
        • Corrected QT interval using Fridericia's formula (QTcF) > 470 msec. Patients with an atrioventricular pacemaker or other condition (for example, right bundle branch block) that renders the QT measurement invalid are an exception and the criterion does not apply.
      • Treatment with any of the following within the specified time frame prior to the first dose of TAS-120:
        • Major surgery within 4 weeks (the surgical incision should be fully healed);
        • Radiotherapy for extended field within 4 weeks or limited field radiotherapy within 2 weeks;
        • Any prior systemic therapy regardless of the stop date, but the patient must have recovered to eligibility levels from prior toxicity;
        • Any investigational agent received within 30 days or 5 half-lives (whichever is shorter);
        • Prior treatment with an FGFR inhibitor.

      Cohort 4 only

      • Prior treatment with fulvestrant, or known hypersensitivity to fulvestrant.
      • A serious illness or medical condition(s) including but not limited to the following:
        • Known acute systemic infection;
        • Myocardial infarction, severe/unstable angina, or symptomatic congestive heart failure within the previous 6 months;
        • History or current evidence of serious uncontrolled ventricular arrhythmia;
        • Chronic diarrhea diseases considered to be clinically significant in the opinion of the Investigator;
        • Congenital long QT syndrome, or any known history of torsade de pointes, or family history of unexplained sudden death;
        • Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or TAS-120 administration, or may interfere with the interpretation of study results, and in the judgment of the Investigator would make the patient inappropriate for entry into this study;
        • Brain metastases that are untreated or clinically or radiologically unstable (that is, have been stable for <1 month);
        • History of another primary malignancy that is currently clinically significant or currently requires active intervention.
      • Pregnant or lactating female
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      Patient-derived Organoid as a New Personalized Tool for Colorectal Cancer Peritoneal Disease Treatment

      A Study to Assess a New Personalized Tool for Colorectal Cancer Peritoneal Disease Treatment

      Joleen Hubbard
      All
      18 years and over
      This study is NOT accepting healthy volunteers
      0000-101127-P01-RST
      19-004196
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      Inclusion Criteria:

      • Age ≥ 18 years old.
      • Metastatic CRC patients with synchronous or metachronous peritoneal metastasis.
      • Patients who plan to undergo either diagnostic laparoscopy with tissue biopsy of the peritoneal metastases or cytoreductive surgery of the peritoneal metastases as part of routine clinical care.
      • Patients willing to consent for biopsy.


      Exclusion Criteria:
       

      • Patients who will not have tissue biopsy from diagnostic laparoscopy or tumor resection from cytoreductive surgery as part of routine clinical care.
      • Women known to be pregnant.
      • Non-English speaking, students, prisoners.
      Cancer, Colon cancer, Peritoneal cancer, Rectal cancer
      Cancer treatment, Digestive system, Malignant neoplasm of colon and/or rectum, Medical Oncology, Secondary malignant neoplasm of colon and/or rectum, Secondary malignant neoplasm of peritoneum
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      A Phase 1/2 Study of GRT-C903/GRT-R904, a Vaccine Targeting Shared Neoantigens, in Combination With Immune Checkpoint Blockade for Patients With Advanced Solid Tumors

      A Study of a Personalized Cancer Vaccine Targeting Shared Neoantigens

      Amit Mahipal
      All
      18 years and over
      Phase 1/2
      This study is NOT accepting healthy volunteers
      0000-101128-P01-RST
      19-008520
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      Inclusion Criteria:
       

      For Phase 1

      • MSS-CRC who are currently receiving systemic treatment with a fluoropyrimidine and oxaliplatin and/or irinotecan that may include a VEGF or EGFR targeting therapy as their 1L or 2L therapy for metastatic disease OR who have experienced disease progression following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan that may include a VEGF or EGFR targeting therapy, but have not initiated a new line of therapy;
      • NSCLC who are currently receiving systemic treatment with an anti-PD-(L)1 antibody in combination with cytotoxic, platinum-based chemotherapy OR who have experienced disease progression following treatment an anti-PD-(L)1 antibody in combination with cytotoxic, platinum-based chemotherapy (or antiPD-(L)1 alone if patient refuses platinum-based chemotherapy), but have not initiated a new line of therapy;
      • PDA who are currently receiving systemic cytotoxic chemotherapy as their 1L therapy for metastatic disease OR who have experienced disease progression on 1L systemic cytotoxic chemotherapy, but have not initiated a new line of therapy;
      • Any solid tumor histology where the patient has experienced disease progression with all available therapies known to confer clinical benefit.

      For Phase 2

      • MSS-CRC who are currently receiving systemic treatment with a fluoropyrimidine and oxaliplatin and/or irinotecan that may include a VEGF or EGFR targeting therapy as their 1L therapy for metastatic disease OR who have experienced disease progression following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan that may include a VEGF or EGFR targeting therapy and have not received additional lines of systemic therapy in the metastatic setting;
      • NSCLC who are currently receiving systemic treatment with an anti-PD-(L)1 antibody in combination with cytotoxic, platinum-based chemotherapy OR who have experienced disease progression following treatment an anti-PD-(L)1 antibody followed by cytotoxic, platinum-based chemotherapy (or anti-PD-(L)1 alone if patient refuses platinum-based chemotherapy) and have not received additional lines of systemic therapy in the metastatic setting (Patients whose tumor harbors KRAS G12C may also receive a targeted therapy that inhibits KRAS G12C as prior therapy in addition to pembrolizumab and platinum-based chemotherapy);
      • PDA who are currently receiving systemic cytotoxic chemotherapy as their 1L therapy for metastatic disease OR who have experienced disease progression on 1L systemic cytotoxic chemotherapy and have received no more than 1 prior line of therapy in the metastatic setting;
      • Any solid tumor histology where the patient has experienced disease progression with all available therapies known to confer clinical benefit.
      • Patient’s tumor possesses one of the mutations as determined per local institutional standard.
      • ≥ 18 years of age.


      Exclusion Criteria:
       

      • Tumors with genetic characteristics as follows:
        • For NSCLC, patients with a known genetic driver alteration in EGFR, ALK, ROS1, RET, or TRK;
        • Patients with known MSI-high disease based on institutional standard.
      • Known exposure to chimpanzee adenovirus within the prior 5 months or any history of anaphylaxis in reaction to a vaccination or hypersensitivity to study drug components.
      • Bleeding disorder (e.g., factor deficiency, coagulopathy) or history of significant bruising or bleeding following IM injections or blood draws.
      • Patient has received prior therapy consisting of anti-CTLA-4, anti-PD-1, anti-PD-L1, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways, with the exception of patients with NSCLC or a mutation-positive solid tumor.
      • History of allogenic/solid organ transplant .
      • Active, known, or suspected autoimmune disease.
      • Active tuberculosis or recent (<2 week) clinically significant infection, or evidence of active hepatitis B or hepatitis C.
      • Known history of positive test for human immunodeficiency (HIV) or known acquired immunodeficiency syndrome (AIDS) Complete inclusion and exclusion criteria are listed in the clinical study protocol.
      Biologic/Vaccine, Administration of antineoplastic agent, Drug therapy, Immunotherapy for cancer, Prescription of therapeutic regimen, Oncolytic virus therapy
      Cancer, Colon cancer, Lung cancer, Non-small cell lung cancer, Pancreatic cancer, Rectal cancer
      Biological therapy for cancer, Cancer treatment, Digestive system, Malignant neoplasm of colon and/or rectum, Malignant tumor of pancreas, Medical Oncology, Metastatic non-small cell lung cancer, Non-small cell lung cancer, Respiratory system, Secondary malignant neoplasm of colon and/or rectum, Secondary malignant neoplasm of pancreas, Solid tumor configuration, Virotherapy
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      Mayo Clinic — Rochester, MN

      Phase 2 Study of Novel SEQUEnced Immunotherapy (Pembrolizumab) With Anti-angiogenesis and Chemotherapy in Advanced Gastric and gastroesophageaL Junction (GEJ) Adenocarcinoma (SEQUEL)

      Novel SEQUEnced Immunotherapy With Anti-angiogenesis and Chemotherapy in Advanced gastroesophageaL Adenocarcinoma (SEQUEL)

      Harry Yoon
      All
      18 years and over
      Phase 2
      This study is NOT accepting healthy volunteers
      0000-101133-P01-RST
      19-010617
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      Inclusion Criteria:

      • Written informed consent and HIPAA authorization for release of personal health information prior to registration.
        • NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
      • Age ≥ 18 years at the time of consent.
      • ECOG Performance Status (PS) of 0-1within 28 days prior to registration.
        • NOTE:  Within 0-3 days prior to the anticipated C1D1, ECOG PS must be 0-1.
      • Archived tumor tissue must be available and identified during screening and shipped after subject registration. If archived tissue is not available and the subject is not undergoing a standard of care biopsy, the subject is not eligible for trial participation.
      • PD-L1 results are required, if available. If PD-L1 testing has not been done, it should be ordered as standard of care prior to C1D1. PD-L1 testing must be performed by a CLIA certified lab using the Dako 22C3 antibody.
      • Histologically or cytologically proven adenocarcinoma of the stomach or GEJ.
      • Metastatic, recurrent, or locally advanced unresectable disease.
      • Measurable disease per RECIST v1.1.
      • Candidate for pembrolizumab, ramucirumab, and paclitaxel.
      • Demonstrate adequate organ function as defined in the table below. All screening labs to be obtained within 28 days prior to registration.
        • NOTE: Labs must also be obtained within 10 days prior to C1D1 treatment.
      • Willingness to provide tissue and blood samples for correlative research purposes.
        • NOTE: Enrollment in parallel biopsy protocol, if open for enrollment, is required. Parallel biopsy protocol entitled: “Exploration of tumor biology in patients with metastatic esophageal and gastric cancer (biorepository protocol for prospective tissue collection)”.
      • Females of childbearing potential must have a negative pregnancy test within 72 hours prior to registration. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
        • NOTE: Females are considered of child bearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months
      • Females of childbearing potential and males must be willing to abstain from heterosexual intercourse or to use 2 forms of effective methods of contraception from the time of informed consent (females)/prior to C1D1 (males) until 120 days after treatment discontinuation.
      • Willingness to return to the enrolling institution for follow up.


      Exclusion Criteria:

      • Past medical history of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease (relevant for ramucirumab).
      • Any of the following cardiac criteria (relevant for ramucirumab):
        • Mean resting corrected QT interval (QTc using Fridericia’s formula) > 470 msec;
        • Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG; e.g., complete left bundle branch block, third degree heart block, second degree heart block, PR interval > 250msec.;
        • Symptomatic heart failure, uncontrolled hypokalemia despite repletion, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives;
          • NOTE: Factors that increase risk of QTc prolongation or risk of arrhythmia, such as concomitant medications, may require increased monitoring during Combination Therapy. 
        • The patient has experienced any arterial thromboembolic events, including but not limited to myocardial infarction, transient ischemic attack, cerebrovascular accident, or unstable angina, within 6 months prior to first dose of protocol therapy;
        • The patient has uncontrolled or poorly-controlled hypertension (> 160 mmHg systolic or > 100 mmHg diastolic for > 4 weeks) despite standard medical management.
      • The patient has experienced any Grade 3-4 GI bleeding within 3 months prior to first dose of protocol therapy (relevant for ramucirumab).
      • Cirrhosis at a level of Child-Pugh B (or worse) or cirrhosis (any degree) and a history of hepatic encephalopathy or clinically meaningful ascites resulting from cirrhosis. Clinically meaningful ascites is defined as ascites from cirrhosis requiring diuretics or paracentesis (relevant for ramucirumab).
      • Any hemoptysis (defined as bright red blood or ≥ 1/2 teaspoon) within 2 months prior to first dose of protocol therapy or with radiographic evidence of intratumor cavitation or has radiologically documented evidence of major blood vessel invasion or encasement by cancer (relevant for ramucirumab).
      • The patient has a prior history of GI perforation/fistula (within 6 months of first dose of protocol therapy) or risk factors for perforation (relevant for ramucirumab).
      • The patient has a serious or nonhealing wound, ulcer, or bone fracture within 28 days prior to first dose of protocol therapy (relevant for ramucirumab).
      • The patient has undergone major surgery within 28 days prior to first dose of protocol therapy prior to the first dose of protocol therapy. The patient has elective or planned major surgery to be performed during the course of the clinical trial (relevant for ramucirumab).
      • Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.
      • Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
        • NOTE: Inhaled steroids or steroid injections for joint disease are allowed.
      • Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
      • Disease progression according to RECIST v1.1 or irRECIST, or treatment intolerance, during prior therapy with an anti-PD-1, anti-PD-L1, or anti- PD-L2 agent.
        • NOTE: Stable or responsive disease on anti-PD-1/L1-L2 therapy (without concurrent cytotoxic therapy) is allowed.
      • Weight loss ≥ 5% during prior anti-PD-1, anti-PD-L1, or anti- PD-L2-containing therapy (from time of initiation of such therapy to most recent dose).
      • Prior therapy combining anti-angiogenesis agent with cytotoxic agent(s).
        • NOTE: Prior single-agent anti-angiogenesis therapy (eg, ramucirumab monotherapy) is allowed.
      • Patients known to be HIV positive.
      • Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
      • Prior severe allergic reactions to a monoclonal antibody or hypersensitivity to pembrolizumab or any of its excipients.
      • Has had a prior anti-cancer monoclonal antibody (mAb) within 3 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 3 weeks earlier.
      • Other active malignancy which requires current treatment and which in the opinion of the site investigator is likely to interfere with evaluation of disease assessment.
        • NOTE: Continuation of hormonal therapies is allowed.
      • Patients with known active central nervous system (CNS) metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
      • Uncontrolled intercurrent illness which in the opinion of the investigator poses unacceptably high risk when combined with study treatment, including but not limited to the following:
        • Symptomatic congestive heart failure;
        • Unstable angina pectoris;
        • Severely impaired lung function
        • Known history of active TB (Bacillus Tuberculosis);
        • Uncontrolled diabetes as defined by fasting serum glucose >1.5 x ULN;
        • NOTE: Optimal glycemic control should be achieved before starting trial therapy.
      • Significant underlying liver disease such as severe cirrhosis or hepatic impairment.
      • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
      • Has an active infection requiring systemic therapy prior to therapy initiation.
      • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject’s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
      • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
      • Has known history of or any evidence of active, non-infectious pneumonitis.
      • Currently uncontrolled hyper/hypothyroidism or hyper/hypocortism if in the opinion of the investigator they pose unacceptably high risk when combined with study treatment.
      • Received live vaccine or live attenuated vaccine within 30 days prior to registration.
        • NOTE: Administration of killed vaccines is allowed.
      • Prior pancreatitis that was symptomatic or required medical intervention ≤ 6 months prior to registration (known toxicity of pembrolizumab).
      • Prior enteritis that was symptomatic or required medical intervention ≤ 6 months prior to registration (known toxicity of pembrolizumab).
      • Pre-existing motor or sensory neurotoxicity grade 3 or higher.
      • For patients who received tive RT, there must be no evidence of disease progression on clinical or imaging exams for at least two weeks prior to first dose of treatment.
      • Parenteral or oral corticosteroids in the last two weeks prior to starting sudy treatment.
      • Prior solid organ or allogeneic transplant.

      Eligibility last updated 10/13/21. Questions regarding updates should be directed to the study team contact.

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      Mayo Clinic — Rochester, MN