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KO-TIP-007: A 2 Cohort, Non-comparative, Pivotal Study Evaluating the Efficacy of Tipifarnib in Patients With Head and Neck Squamous Cell Carcinoma (HNSCC) With HRAS Mutations (AIM-HN) and the Impact of HRAS Mutations on Response to First Line Systemic Therapies for HNSCC (SEQ-HN) (AIM-HN/SEQ-HN)

A Study to Evaluate the Safety and Effectiveness of Tipifarnib in Head and Neck Cancer With HRAS Mutations and Impact of HRAS on Response to Therapy

Katharine Price
All
18 years and over
Phase 2
This study is NOT accepting healthy volunteers
0000-100701-P01-RST
18-008378
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Inclusion Criteria:

•AIM-HN

  • Histologically confirmed head and neck cancer (oral cavity, pharynx, larynx, sinonasal, nasopharyngeal, or unknown primary) of squamous histology not amenable to local therapy with curative intent (surgery or radiation therapy with or without chemotherapy).
  • Documented treatment failure from most recent prior therapy (e.g. tumor progression, clinical deterioration, or recurrence), and from at least one prior platinum-containing regimen in any treatment setting.
  • Known tumor missense HRAS mutation.
  • Measurable disease by RECIST v1.1.
  • ECOG performance status of 0-1.
  • Acceptable liver, renal and hematological function.


Exclusion Criteria:

•AIM-HN

  • Has disease that is suitable for local therapy administered with curative intent.
  • Histologically confirmed salivary gland, thyroid, (primary) cutaneous squamous or nonsquamous histologies (e.g., mucosal melanoma).
  • Known additional malignancy that is progressing or requires active treatment (excluding non-melanoma skin cancer, adjuvant hormonal therapy for breast cancer and hormonal treatment for castration sensitive prostate cancer).
  • Ongoing treatment with an anticancer agent not contemplated in this protocol (excluding adjuvant hormonal therapy for breast cancer and hormonal treatment for castration sensitive prostate cancer).
  • Prior treatment (at least 1 full treatment cycle) with a farnesyltransferase inhibitor (FTI).
  • Any use of investigational therapy within 2 weeks of Cycle 1 Day 1 (C1D1) or 5 half-lives (whichever is longer).
  • Received treatment for unstable angina within prior year, myocardial infarction within the prior year, cerebro-vascular attack within the prior year, history of New York Heart Association grade III or greater congestive heart failure, or current serious cardiac arrhythmia requiring medication except atrial fibrillation.
  • Non-tolerable Grade 2 or ≥ Grade 3 neuropathy or evidence of unstable neurological symptoms within 4 weeks of Cycle 1 Day 1.
  • Major surgery, other than diagnostic surgery, within 2 weeks prior to Cycle 1 Day 1, without complete recovery.
  • Active, uncontrolled bacterial, viral or fungal infections requiring systemic therapy, including known history of infection with human immunodeficiency virus or an active infection with hepatitis B or hepatitis C.
  • Subjects who have exhibited allergic reactions to tipifarnib or structural compounds similar to tipifarnib or to its excipients.
  • Required use of concomitant medications classified as strong inhibitors or inducers of cytochrome P450 3A4 or UDP-glucuronosyltransferase (UGT).
  • Concomitant disease or condition that could interfere with the conduct of the study or that would, in the opinion of the investigator, pose an unacceptable risk to the subjects in this study.
  • Female subjects who are pregnant or lactating

Inclusion Criteria:
SEQ-HN

  • Histologically confirmed head and neck cancer (oral cavity, pharynx, larynx, sinonasal, nasopharyngeal, or unknown primary) of squamous histology.
  • HRAS wildtype determined by a test
  • Will or has received at least one systemic anti-cancer therapy for recurrent or metastatic HNSCC.


Exclusion Criteria:
SEQ-HN

  • Histologically confirmed salivary gland, thyroid, (primary) cutaneous squamous or nonsquamous histologies (e.g., mucosal melanoma).
  • Concomitant disease or condition that could interefere with the conduct of the study or that would, in the opinion of the investigator, pose an unacceptable risk to the subject in this study.
Device, Drug, Administration of antineoplastic agent, Drug therapy
Cancer, Cancer of unknown origin, Head and neck cancer, Laryngeal cancer, Nasopharyngeal carcinoma, Squamous cell carcinoma of the skin
Cancer treatment, Digestive system, Integumentary system, Medical Oncology, Respiratory system, Squamous cell carcinoma of head and neck
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Mayo Clinic — Rochester, MN

MC18C1, Prevention of Paclitaxel-associated Neuropathy with Fingolimod: A Pilot Trial (MC18C1)

A Study to Evaluate Prevention of Paclitaxel-Associated Neuropathy with Fingolimod

Charles Loprinzi
All
18 years and over
Phase 1
This study is NOT accepting healthy volunteers
0000-100721-P01-RST
19-000917
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Inclusion Criteria:

  • Age ≥ 18 years.
  • Ability to complete questionnaires by themselves or with assistance.
  • Paclitaxel at a dose of 80 mg/m^2 given every week for a scheduled course of 12 weeks for treating breast cancer.
  • Life expectancy ≥ 6 months.
  • ECOG Performance Status (PS) 0, 1.
  • Negative pregnancy test (serum or urine) done ≤ 14 days prior to registration, for persons of childbearing potential only.
  • Provide written informed consent.


Exclusion Criteria:

  • Previous exposure to paclitaxel (please note that it is acceptable for patients to receive non-neurotoxic chemotherapy, like AC, before or after the weekly paclitaxel and/or to receive concurrent anti-her 2 therapy).
  • Any of the following because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects:
    • Pregnant persons;
    • Nursing persons;
    • Persons of childbearing potential who are unwilling to employ adequate contraception.
  • Previous diagnosis of diabetic or other peripheral neuropathy.
  • Current or previous use of fingolimod.
  • History of the following preexisting conditions: ischemic heart disease, cardiac arrest, cerebrovascular disease, uncontrolled hypertension, symptomatic bradycardia, macular edema, recurrent syncope, severe untreated sleep apnea, herpes zoster, chronic hepatitis, tuberculosis, systemic fungal infections, skin cancer, or insulin-dependent diabetes.
  • Myocardial infarction, unstable angina, stroke, TIA, decompensated heart failure requiring hospitalization or Class III/IV heart failure < 6 months prior to registration.
  • History or presence of Mobitz Type II second-degree or third-degree AV block or sick sinus syndrome, unless patient has a functioning pacemaker.
  • History of a hypersensitivity reaction to fingolimod or any of the excipients including rash, urticarial, and angioedema upon treatment initiation.
  • Baseline QTC interval ≥ 450 ms (on EKG).
  • Concurrent use of a class Ia or III antiarrhythmic.
  • Drugs with a KNOWN risk of torsades de pointes (Information regarding drug specific risk of QT prolongation can be found at www.crediblemeds.org).
  • Concurrent use of beta blockers, calcium channel blockers or digoxin.
  • Use of immunosuppressive, or immune-modulating therapies that may have immunosuppressive effects.
  • Immunocompromised patients including patients known to be HIV positive.
  • Uncontrolled intercurrent illness including, but not limited to:
    • ongoing or active infection;
    • unstable angina pectoris;
    • cardiac arrhythmia;
    • psychiatric illness/social situations that would limit compliance with study requirements.
  • Receiving any other investigational agent.
  • Family history of a genetic/familial neuropathy.
  • Received a vaccine (inactivated) ≤ 14 days prior to registration.
  • Positive varicella zoster IgM titer, consistent with recent exposure.
Drug, Other, Drug therapy
Breast cancer, Cancer, Cancer-related pain, Peripheral neuropathy
Cancer treatment, Chemotherapy, Chemotherapy for breast cancer, Malignant neoplastic disease, Medical Oncology, Nervous system, Peripheral nervous system, Peripheral neuropathy due to and following chemotherapy, fingolimod, paclitaxel, Fingolimod, Infinnium
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Mayo Clinic — Rochester, MN

MC18C2, Treatment of Established Chemotherapy-induced Neuropathy with Fingolimod: A Pilot Trial (MC18C2)

A Study to Evaluate Treatment of Established Chemotherapy-induced Neuropathy with Fingolimod

Charles Loprinzi
All
18 years and over
Early Phase 1
This study is NOT accepting healthy volunteers
0000-100722-P01-RST
19-001371
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Inclusion Criteria:

  • Age ≥ 18 years old.
  • Pain or symptoms of CIPN of ≥ 3 months duration, for which the patient wants intervention.
    • NOTE: Neurotoxic chemotherapy must have been completed ≥ 3 months (93 days) prior to registration and there must be no further planned neurotoxic chemotherapy for > 2 months after registration.
  • Tingling, numbness or pain was at least a four out of ten problem during the week prior to registration, on a 0-10 scale where zero was no problem and ten was the worst possible problem (patient verbal report to clinician utilizing question in Appendix VI).
  • ECOG Performance Status (PS) 0, 1 or 2.
  • Negative pregnancy test done ≤ 14 days prior to registration, for persons of childbearing potential only.
  • Provided written informed consent.
  • Ability to complete questionnaire(s) by themselves or with assistance.
  • Life expectancy ≥ 6 months.


Exclusion Criteria:

  • Any of the following because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects:
    • Pregnant persons;
    • Nursing persons;
    • Persons of childbearing potential who are unwilling to employ adequate contraception.
  • Previous diagnosis of diabetic or other peripheral neuropathy.
  • Current or previous use of fingolimod.
  • History of the following preexisting conditions: ischemic heart disease, cardiac arrest, cerebrovascular disease, uncontrolled hypertension, symptomatic bradycardia, macular edema, recurrent syncope, severe untreated sleep apnea, Herpes simplex virus (HSV) varicella zoster (VZV), chronic hepatitis, tuberculosis, fungal infections, skin cancer, or diabetes.
  • Myocardial infarction, unstable angina, stroke, TIA, decompensated heart failure requiring hospitalization or Class III/IV heart failure < 6 months prior to registration.
  • History or presence of Mobitz Type II second degree or third degree AV block or sick sinus syndrome, unless patient has a functioning pacemaker.
  • History of hypersensitivity reaction to fingolimod or any of the excipients including rash, urticarial, and angioedema upon treatment initiation.
  • Baseline QTc interval ≥ 450 ms (on patient EKG)
  • Concurrent use of a class Ia or III antiarrhythmic drug
  • Drugs with a known risk of torsades de pointes
  • Concurrent use of beta blockers, calcium channel blockers, or digoxin
  • Use of immunosuppressive or immune-modulating therapies that may have immunosuppressive effects
  • Immunocompromised patients including patients known to be HIV positive.
  • Uncontrolled intercurrent illness including, but not limited to:
    • ongoing or active infection;
    • unstable angina pectoris;
    • cardiac arrhythmia;
    • or psychiatric illness/social situations that would limit compliance with study requirements.
  • Family history of genetic/familial neuropathy.
  • Currently receiving another agent to treat CIPN, such as duloxetine, gabapentin or pregabalin, and not willing to be weaned off of these medications prior to therapy initiation.
  • History of peripheral neuropathy prior to receiving neurotoxic chemotherapy.
  • Received a vaccine (inactivated) ≤ 2 weeks prior to registration.
  • Positive varicella zoster IgM titer, consistent with recent exposure.
Drug, Other, Drug therapy
Cancer
Cancer treatment, Chemotherapy, Malignant neoplastic disease, Medical Oncology, Peripheral neuropathy due to and following chemotherapy, fingolimod
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TNB383B.0001 - A Multicenter, Phase 1, Open-label, Dose-escalation and Expansion Study of TNB-383B, a Bispecific Antibody Targeting BCMA in Subjects With Relapsed or Refractory Multiple Myeloma

A Study of TNB-383B in Subjects With Relapsed or Refractory Multiple Myeloma

Shaji Kumar
All
18 years and over
Phase 1/2
This study is NOT accepting healthy volunteers
0000-100731-P01-RST
19-001323
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Inclusion Criteria:
 

  • Subject must be ≥ 18 years of age.
  • Three or more prior lines of therapy with exposure to a PI, an IMiD, and an anti-CD38 antibody (e.g., daratumumab). In order to be eligible for this study subjects must not be candidates for treatment regimens known to provide clinical benefit in MM.
  • Subject has an Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2.
  • Subject is capable of understanding and complying with parameters as outlined in the protocol and able to sign informed consent.
  • Subject must have adequate bone marrow function, defined as:
    • absolute neutrophil count (ANC) ≥ 1000/mm^3;
    • platelets ≥ 50,000/mm^3;
    • hemoglobin ≥ 8.0 g/dL;
    • Transfusion and / or growth factor support is permitted prior to assessment, but neutrophils, platelets, and hemoglobin must be stable for at least 72 hours after transfusion and / or growth factor administration prior to Screening for the subject to be eligible.
  • Subject must have an eGFR ≥ 30 mL/min as estimated by the MDRD formula.
  • Subject must have total bilirubin ≤ 1.5 × upper limit of normal (ULN; except if the subject has a known diagnosis of Gilbert’s syndrome, in which case bilirubin must be < 3 x ULN).
  • Serum calcium (corrected for albumin) at or below the ULN range (subject may enroll in the setting of hypercalcemia at Screening IF hypercalcemia resolves with standard treatment by Cycle 1 Day 1) prior to study therapy initiation.
  • Measurable Disease: Subject has a diagnosis of MM and documented prior treatment with a PI, an IMiD, and an anti-CD38 mAb (ie, daratumumab) as part of 3 or more lines of therapy. In order to be eligible for this study subjects must not be candidates for treatment regimens known to provide clinical benefit in MM. There is no maximum number of prior regimens and prior bone marrow transplant is acceptable if subject is > 12 weeks (autologous) or > 1 year (allogeneic) status-post transplantation.
  • Measurable disease is defined as at least 1 of the following:
    • Serum M-protein ≥ 0.5 g/dL (≥ 5 g/L);
    • Urine M-protein ≥ 200 mg / 24h;
    • Serum free light chain (FLC) assay: Involved FLC level ≥ 10 mg/dl (≥ 100 mg/L) and an abnormal serum FLC ratio (< 0.26 or > 1.65).
  • Subject has confirmed evidence of relapse / progression from the immediately prior MM therapy, or subject is relapsed / refractory to the immediately prior MM therapy. (‘Refractory’ is defined as subjects with either progressive disease or best response of stable disease to the last therapy; ‘Relapsed / refractory’ is defined as subjects with a history of minimal response [MR] or better response to prior therapy, now with disease progression within 60 days of the last therapy. ‘Relapse’ is defined as previously treated myeloma that progresses and requires initiation of salvage therapy, without meeting IMWG uniform response criteria for relapsed / refractory).
  • Subject has adequate archival tumor bone marrow tissue if available or consents to a fresh pre- treatment bone marrow tumor biopsy.


Exclusion Criteria:

  • Subject has been diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of basal cell or squamous cell carcinoma of the skin, in situ malignancy, low-risk prostate carcinoma after curative therapy, or complete resection / curative therapy of an advanced malignancy.
  • Subject has a history of central nervous system (CNS) involvement by their myeloma.
  • Subject has a history of Grade ≥ 3 peripheral neuropathy.
  • Subject has a history of plasma cell leukemia, POEMS syndrome, or amyloidosis.
  • Subject has received another investigational drug within 21 days of enrollment.
  • Subject has ever received BCMA-targeted therapy. Subjects who have received targeted therapy against non-BCMA targets will not be excluded.
  • Subject has received a peripheral autologous stem cell transplant within 12 weeks or an allogeneic stem cell transplant within 1 year of the first dose of study drug treatment.
  • Subject has any medical or psychiatric condition which in the opinion of the investigator or Study Medical Monitor places the subject at an unacceptably high risk for toxicities, could interfere with successful or safe delivery of therapy, or could interfere with evaluation of the investigational product or interpretation of subject safety or study results. Examples include history of significant mucosal / internal bleeding, major psychiatric illness, drug abuse (including active alcoholism), or known allergy or hypersensitivity to components of the study drug formulation.
  • Subject has received any therapy to treat cancer (including radiation, chemotherapy, biologics, cellular therapies and / or steroids at doses > 20 mg dexamethasone or equivalent) or undergone a major surgical procedure within 21 days, or within 5 half-lives of an anti-cancer drug, prior to the first dose of study treatment, whichever is shorter.
  • Subject has known infection Grade ≥ 2 requiring anti-infective treatment. Upon completion of antibiotics and resolution to Grade ≤ 1, the subject is considered eligible for the study from an infection standpoint.
  • Confirmed positive test results for human immunodeficiency virus (HIV), or subjects with chronic or active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV). Subjects who have a history of HBV or HCV who have documented cures (HBV: hepatitis B surface antigen [HBsAg] negative; HCV: undetectable HCV RNA 24 weeks after the end of treatment) may be enrolled.
  • Major cardiac abnormalities such as but not limited to the following: uncontrolled angina or unstable life-threatening arrhythmias, history of myocardial infarction ≤ 12 weeks before Screening, Class ≥ 3 New York Heart Association congestive heart failure, severe cardiac insufficiency, or persistent QTc prolongation (> 480 msec, QTc Fridericia).
  • If female, subject must not be pregnant or breastfeeding and be either postmenopausal (for at least 12 consecutive months), OR permanently surgically sterile OR for women of childbearing potential practicing at least 1 protocol specified method of female birth control AND 1 protocol specified method of male birth control (vasectomy or condoms), starting at Screening through at least6 months after the last dose of study drug.
  • Subject has unresolved AEs ≥ Grade 2 (NCI CTCAE v5.0) from prior anticancer therapy except for:
    • Alopecia;
    • Peripheral neuropathy (peripheral neuropathy ≥ Grade 3 will be excluded);
    • Anemia or thrombocytopenia (the latter cytopenias must be Grade 4 to trigger exclusion, Grade 3 with symptoms or bleeding, respectively, or return within 72 hours despite transfusion support);
    • Subjects with irreversible toxicity not reasonably expected to be exacerbated by any of the investigational products may be included (e.g., hearing loss) after consultation with the Study Medical Monitor.

Eligibility last updated 2/11/22. Questions regarding updates should be directed to the study team contact.

Drug, Administration of antineoplastic agent, Drug therapy
Cancer, Multiple myeloma
Cancer treatment, Hematopoietic system, Medical Oncology, Relapse multiple myeloma
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Phase II Pre-emptive OsciLLation of ER activitY Levels Through Alternation of Estradiol/Anti-estrogen Therapies Prior to Disease Progression in ER/HER2- Metastatic or Advanced Breast Cancer (POLLY)

A Study to Evaluate Estrogen Receptor (ER) Reactivation Therapy for Breast Cancer

Karthik Giridhar
Female
18 years and over
Phase 2
This study is NOT accepting healthy volunteers
0000-100734-P01-RST
18-010102
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Inclusion Criteria:

  • Women ≥ 18 years of age with clinical stage IV ER+/HER2- breast cancer, or with locally recurrent ER+/HER2- disease not amenable to therapy for curative intent.
  • Patient must have been treated with an anti-estrogen at any time in their disease history. Combination regimens that include an anti-estrogen and any biologic, or targeted therapy, are permitted (e.g., any CDK inhibitor, everolimus, or any other novel biologics), and are considered to be a single hormonal therapy based regimen.
    • Any number of prior lines of anti-estrogen (i.e., hormonal) therapy is permissible. 
    • One line of prior chemotherapy for advanced/metastatic disease is permissible.
  • Histologic documentation of ER strongly+/HER2- breast cancer by core needle biopsy, fine needle aspiration, incisional biopsy, or surgical biopsy of ≥1 site(s) of metastatic or locally advanced disease performed as standard of care within the past 4 months for assessment of eligibility for study participation (except as noted below in c/d/e).
    • ER strongly+ status defined as ER staining by immunohistochemistry in ≥ 50% of malignant cell nuclei with an intensity ≥ 2+ on a scale of 0-3+. These criteria are equivalent to an Allred score ≥ 6.
    • HER2-negative status is defined as immunohistochemistry score of 0-1+, or with a FISH ratio of < 2 if IHC is 2+ or if IHC has not been done (as per ASCO/CAP definitions). In cases of borderline or equivocal HER2 status, eligibility will be determined by the PI.
    • Archived tumor specimens: Excess tumor tissue must be available for research purposes. This will include tumor tissue sufficient to make ≥ 10 five-micron sections; more tumor tissue is preferred. Freshly acquired tumor specimens: As part of a clinically indicated biopsy procedure, an additional 1-3 cores or tissue fragments will be obtained by core needle or surgical biopsy for research purposes and FFPE.
    • Patients with bone-only metastatic disease with a history of ER+/HER2- breast cancer are eligible, and bone biopsy is not required, providing their primary cancer is consistent with the above-described ER and HER2 criteria.
    • Patients with non-bone metastatic disease in whom a safe and accurate biopsy of recurrent/metastatic disease cannot be readily obtained are also eligible, providing their primary cancer is consistent with the above-described ER and HER2 criteria.
    • Patient must be a candidate for treatment with 17B-estradiol and an aromatase inhibitor.
    • If the most recent therapy was in the adjuvant setting, the recurrence-free interval (time from initiation of adjuvant anti-estrogen therapy to clinical evidence of disease recurrence) must have been ≥ 2 years. If the most recent therapy was in the advanced/metastatic setting, the progression-free interval must have been ≥ 4 months (except in the case of investigational hormonal therapies).
    • Patient must be post-menopausal based on either a history of an oophorectomy, or ≥ 1 year of amenorrhea. An elevated serum gonadotropin level and estradiol level in the postmenopausal range (as locally defined) can be used to confirm menopausal status in a subject with < 1 year of amenorrhea.
    • Baseline radiographic staging, including specifically either PET/CT, or CT (CAP) and bone scan.
    • Patient must be capable and willing to provide informed written consent for study participation.
    • The following laboratory values must be confirmed for eligibility within 28 days prior to initiation of study therapy:
      • Hematology panel
        • hemoglobin > 9 g/dL;
        • white blood cell (WBC) count (≥ 2,000/uL);
        • platelet count ≥ 75,000/uL.
      • Serum biochemistry/metabolic panel 
        • creatinine ≤ 1.5 x upper limits of normal (ULN);
        • total bilirubin ≤ 1.5 x upper limits of normal (ULN);
        • ALT and AST ≤ 3.0 x upper limits of normal (ULN) For patients with liver metastasis: < 5 x upper limits of normal (ULN).


Exclusion Criteria:

  • Treatment with fulvestrant within 16 weeks prior to study enrollment.
  • Any other concurrent systemic anti-cancer treatments, including conventional chemotherapeutic agents and biological agents, during the study period.
    • Anti-resorptive bone therapies (e.g., bisphosphonates, denosumab) are permitted.
  • Any investigational cancer therapy in the last 3 weeks.
  • Known CNS disease, unless clinically stable for ≥ 3 months.
  • History of any of the following:
    • deep venous thrombosis;
    • pulmonary embolism;
    • stroke;
    • acute myocardial infarction;
    • congestive heart failure;
    • previous malignancy not treated with curative intent, or with an estimated recurrence risk ≥ 30%.
Drug
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Multiparametric MRI (mpMRI) for Preoperative Staging and Treatment Planning for Newly-Diagnosed Prostate Cancer

A Study to Assess Multiparametric MRI in Evaluating Cancer Stage and Helping Treatment Planning in Patients with Prostate Cancer

Adam Froemming
Male
18 years and over
Phase 2
This study is NOT accepting healthy volunteers
0000-100741-P01-RST
18-010338
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Inclusion Criteria:

  • Recently diagnosed with prostate cancer for whom definitive surgical treatment is indicated.


Exclusion Criteria:
 

  • Not suitable to undergo MRI or receive gadolinium-based contrast agent (severe, untreatable claustrophobia; MRI-incompatible metallic objects or implanted medical devices; renal failure; weight greater than allowable by scanner per institutional standard practice).
  • Prior surgical and/or non-surgical treatment for prostate cancer.
  • Prior hip replacement or other major pelvic surgery
Procedure/Surgery, Multiparametric MRI of prostate
Cancer, Prostate cancer
Cancer treatment, MRI, Malignant tumor of prostate, Medical Oncology, Reproductive system
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A Prospective Comparative Study of Outcomes with Proton and Photon Radiation in Prostate Cancer (COMPPARE) (COMPPARE)

A Study Comparing Proton and Photon Radiation Outcomes in Prostate Cancer Patients

Chunhee Choo
All
30 years to 85 years old
Not Applicable
This study is NOT accepting healthy volunteers
0000-100744-P01-RST
18-008447
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Inclusion Criteria:


- Diagnosis of adenocarcinoma of the prostate.

- 30-85 years of age at the time of consent with a life expectancy estimation (LEE) of ≥ 8 years.

- Localized prostate cancer, as confirmed by staging with PSA, biopsy, Gleason score, DRE with or without mpMRI, and clinical stage.

- Very low-risk, low-risk, intermediate-risk, or high-risk disease based on NCCN Prostate Cancer Risk Group Guidelines and Joint AUA/ASTRO/SUO Guidelines.

- If patient has high-risk disease, nuclear medicine bone imaging must be performed to document the absence of overt metastatic disease in bones.

- ECOG/Zubrod Performance Status 0
•2.

- Candidate for definitive prostate radiotherapy (either IMRT or proton).

- If patient is to be treated with IMRT, all treatment must be planned with IMRT; if patient is to be treated with protons, all treatment must be planned with protons (including pelvic nodes if treated).


Exclusion Criteria:


- Findings of metastatic disease (nodal or distant, N1 or M1).

- Very high-risk prostate cancer based on NCCN Prostate Cancer Risk Group Guidelines and Joint AUA/ASTRO/SUO Guidelines.

- Prior procedures for treatment of prostate cancer, such as radical or robotic prostatectomy, high-intensity focused ultrasound, cryosurgery, or focal prostatectomy
[note that procedures used for benign prostatic hyperplasia symptoms, such as transurethral resection of the prostate (TURP) and GreenLight Laser Therapy, are acceptable].

- Previous prostate cancer treatment with the exception of ADT according to NCCN guidelines.

- History of invasive rectal malignancy or other malignancy in the true pelvis (e.g. bladder, rectum, or reproductive organs), regardless of disease-free interval.

- Active inflammatory bowel disease (i.e., patients requiring medical interventions or who are symptomatic).

- Prior pelvic RT for any reason.

- Documented lack of psychological ability or general health permitting completion of the study requirements and required follow-up.

- Documented diminished capacity to understand the risks and benefits of participation in research and to autonomously provide informed consent.

In addition, because the embedded randomized controlled trial compares fractionation schemes, patients who are receiving pelvic node irradiation may not be enrolled on the
randomized controlled trial.

Radiation, Assessment of quality of life, Intensity modulated radiation therapy, Proton therapy
Cancer, Prostate cancer
Adenocarcinoma of prostate, Cancer treatment, IMRT, Medical Oncology, Proton therapy, Radiation therapy, Reproductive system
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A Prospective Comparative Study of Outcomes with Proton and Photon Radiation in Prostate Cancer (COMPPARE) (COMPPARE)

A Study Comparing Proton and Photon Radiation Outcomes in Prostate Cancer Patients

Ron Smith
All
30 years to 85 years old
Not Applicable
This study is NOT accepting healthy volunteers
0000-100744-P01-MAIJ
18-008447
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Inclusion Criteria:


- Diagnosis of adenocarcinoma of the prostate.

- 30-85 years of age at the time of consent with a life expectancy estimation (LEE) of ≥ 8 years.

- Localized prostate cancer, as confirmed by staging with PSA, biopsy, Gleason score, DRE with or without mpMRI, and clinical stage.

- Very low-risk, low-risk, intermediate-risk, or high-risk disease based on NCCN Prostate Cancer Risk Group Guidelines and Joint AUA/ASTRO/SUO Guidelines.

- If patient has high-risk disease, nuclear medicine bone imaging must be performed to document the absence of overt metastatic disease in bones.

- ECOG/Zubrod Performance Status 0
•2.

- Candidate for definitive prostate radiotherapy (either IMRT or proton).

- If patient is to be treated with IMRT, all treatment must be planned with IMRT; if patient is to be treated with protons, all treatment must be planned with protons (including pelvic nodes if treated).


Exclusion Criteria:


- Findings of metastatic disease (nodal or distant, N1 or M1).

- Very high-risk prostate cancer based on NCCN Prostate Cancer Risk Group Guidelines and Joint AUA/ASTRO/SUO Guidelines.

- Prior procedures for treatment of prostate cancer, such as radical or robotic prostatectomy, high-intensity focused ultrasound, cryosurgery, or focal prostatectomy
[note that procedures used for benign prostatic hyperplasia symptoms, such as transurethral resection of the prostate (TURP) and GreenLight Laser Therapy, are acceptable].

- Previous prostate cancer treatment with the exception of ADT according to NCCN guidelines.

- History of invasive rectal malignancy or other malignancy in the true pelvis (e.g. bladder, rectum, or reproductive organs), regardless of disease-free interval.

- Active inflammatory bowel disease (i.e., patients requiring medical interventions or who are symptomatic).

- Prior pelvic RT for any reason.

- Documented lack of psychological ability or general health permitting completion of the study requirements and required follow-up.

- Documented diminished capacity to understand the risks and benefits of participation in research and to autonomously provide informed consent.

In addition, because the embedded randomized controlled trial compares fractionation schemes, patients who are receiving pelvic node irradiation may not be enrolled on the
randomized controlled trial.

Radiation, Assessment of quality of life, Intensity modulated radiation therapy, Proton therapy
Cancer, Prostate cancer
Adenocarcinoma of prostate, Cancer treatment, IMRT, Medical Oncology, Proton therapy, Radiation therapy, Reproductive system
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Mayo Clinic Health System — Mankato, MN

A Phase III, Double-Blinded, Multicenter, Randomized Study Evaluating the Efficacy and Safety of Neoadjuvant Treatment With Atezolizumab or Placebo in Combination With Platinum-Based Chemotherapy in Patients With Resectable Stage II, IIIA, or Select IIIB Non−Small Cell Lung Cancer

A Study of Neoadjuvant Atezolizumab Plus Chemotherapy Versus Placebo Plus Chemotherapy in Patients With Resectable Stage II, IIIA, or Select IIIB Non-Small Cell Lung Cancer (IMpower030)

Aaron Mansfield
All
18 years and over
Phase 3
This study is NOT accepting healthy volunteers
0000-100766-P01-RST
18-000521
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Inclusion Criteria:

  • Age ≥ 18 years at time of signing Informed Consent Form
  • Ability to comply with the study protocol, in the investigator’s judgement
  • Pathologically documented Stage II, IIIA, or select IIIB (T3N2 only) NSCLC of squamous or non-squamous histology
  • Staging should be based on the 8th edition of the American Joint Committee on Cancer (AJCC) / Union Internationale Contre le Cancer (UICC) NSCLC staging system.
    • T4 primary NSCLC will be allowed only on the basis of size (tumors > 7 cm). Invasion of the diaphragm, mediastinum, heart, great vessels, trachea, recurrent laryngeal nerve, esophagus, vertebral body, carina, and separate tumor nodules in a different ipsilateral lobe is not permitted.
  • Patients with mixed NSCLC histology (squamous and non-squamous) or NSCLC not otherwise specified are eligible.
  • Patients may be screened based on clinical stage, but mandatory preoperative documentation of N2 nodal involvement by invasive mediastinal staging; e.g., CT-guided biopsy, endobronchial ultrasound (EBUS), mediastinoscopy, is required for PET-positive N2 nodes. Pre-operative staging of levels 5/6 nodes is optional.
  • Solid or subsolid appearance of NSCLC on CT scan with no appearance of purely ground-glass opacity (GGO)
  • For subsolid lesions, the tumor size (i.e., clinical T stage) should be measured based on solid component only, exclusive of the GGO component.
  • Evaluation by the operating attending surgeon and involved medical oncologist prior to study enrollment to verify study eligibility for R0 resection with curative intent 
  • PFTs within 6 months of planned resection and repeated at screening, if clinically indicated, including lung volumes, spirometry, and a diffusion capacity
    • If PFTs were performed before 6 months of planned resection or have never been performed, they must be performed during the screening period.
    • Abnormal PFTs may be further evaluated with quantitative ventilation/perfusion scanning or cardiopulmonary exercise testing.
    • Postoperative percent predicted forced expiratory volume in 1 second (FEV1) and diffusion capacity must be ≥ 40% and/or maximal oxygen consumption (VO2max) should be > 10 mL/kg/min.
  • Adequate cardiac function to be eligible for surgical resection with curative intent If clinically indicated, patients with underlying ischemic, valvular, or other significant heart diseases should be evaluated preoperatively by a cardiologist.
  • Measurable disease as assessed by the investigator per RECIST v1.1
  • Eligibility to receive a platinum-based chemotherapy regimen
  • Availability of a representative tumor specimen suitable for determination of PD-L1 status via central testing (results of PD-L1 testing are not required for patient to be randomized into the study)
  • A formalin-fixed paraffin-embedded (FFPE) tumor specimen in a paraffin block (preferred) or at least a minimum of 3 slides containing unstained, freshly cut, serial sections must be submitted along with an associated pathology report before or within 4 weeks after randomization. Any additional slides beyond the required minimum of 3 slides are strongly encouraged for other exploratory biomarker research. If archival tumor tissue is unavailable, tumor tissue must be obtained from a biopsy performed at screening.
  • ECOG Performance Status of 0 or 1
  • Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 14 days prior to initiation of study treatment:
    • ANC ≥ 1.5 x 109/L (1500/µL) without granulocyte colony-stimulating factor support
    • Lymphocyte count ≥ 0.5 x 109/L (500/µL)
    • Platelet count  ≥ 100 x 109/L (100,000/µL) without transfusion
    • Hemoglobin  ≥ 90 g/L (9.0 g/dL)
      • Patients may be transfused to meet this criterion.
    • AST, ALT, and ALP ≤ 2.5 x upper limit of normal (ULN)
    • Serum bilirubin ≤ 1.5 x ULN with the following exception:
      • Patients with known Gilbert disease: serum bilirubin level ≤ 3 x ULN
    • Creatinine clearance ≥ 45 mL/min (calculated using the Cockcroft-Gault formula)
      • For patients intended to receive cisplatin: creatinine clearance ≥ 60 mL/min
    • Serum albumin ≥ 25 g/L (2.5 g/dL)
    • For patients not receiving therapeutic anticoagulation: INR or aPTT ≤ 1.5 x ULN
  • For patients receiving therapeutic anticoagulation: stable anticoagulant regimen
  • Negative HIV test at screening
  • Negative hepatitis B surface antigen (HBsAg) test at screening
  • Negative total hepatitis B core antibody (HBcAb) test at screening, or a positive total HBcAb test followed by a negative hepatitis B virus (HBV) DNA test at screening
    • The HBV DNA test will be performed only for patients who have a positive total HBcAb test.
  • Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening
    • The HCV RNA test will be performed only for patients who have a positive HCV antibody test.
  • For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating eggs, as defined below:
    • Women must remain abstinent or use contraceptive methods with a failure rate of < 1% per year during the treatment period and for 5 months after the last dose of atezolizumab, 30 days after the last dose of nab-paclitaxel, or 6 months after the last dose of pemetrexed, gemcitabine, carboplatin, or cisplatin, whichever is later. Women must refrain from donating eggs during this same period.
    • A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and has not  undergone surgical sterilization (removal of ovaries and/or uterus). The definition of childbearing potential may be adapted for alignment with local guidelines or requirements.
    • Examples of contraceptive methods with a failure rate of < 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices.
    • The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.
  • For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm, as defined below:
    • With female partners of childbearing potential or pregnant female partners, men must remain abstinent or use a condom during the treatment period for 6 months after the last dose of nab-paclitaxel, pemetrexed, gemcitabine, carboplatin, or cisplatin, whichever is later, to avoid exposing the embryo. Men must refrain from donating sperm during this same period.
    • The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods)  and withdrawal are not acceptable methods of contraception of preventing drug exposure.


Exclusion Criteria:

  • Illness or condition that may interfere with a patient’s capacity to understand, follow, and/or comply with study procedures.
  • Any prior therapy for lung cancer, including chemotherapy, or radiotherapy.
  • Major surgical procedure, other than for diagnosis, within 28 days prior to initiation of study treatment, or anticipation of need for non-protocol-mandated major surgical procedure during the study.
  • Non-squamous NSCLC histology with an activating mutation in the epidermal growth factor receptor (EGFR) or with an anaplastic lymphoma kinase (ALK) fusion oncogene.
    • Patients with non-squamous NSCLC histology that have unknown EGFR and/or ALK status require test results at screening. ALK and/or EGFR may be assessed locally or at a central laboratory (for China, testing will only be performed at a central laboratory);
    • If samples are submitted for central testing, additional tissue, cytology, and/or plasma samples are required.
  • Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis, with the following exceptions:
    • Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study;
    • Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study;
    • Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:
      • Rash must cover < 10% of body surface area;
      • Disease is well controlled at baseline and requires only low-potency topical corticosteroids;
      • No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months.
  • History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan.
  • Active tuberculosis.
  • Significant cardiovascular disease (such as New York Heart Association Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident) within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina.
  • History of malignancy other than NSCLC within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate > 90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer.
  • Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia.
  • Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment.
    • Patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study.
  • Prior allogeneic stem cell or solid organ transplantation
  • Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications.
  • Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the last dose of atezolizumab.
  • Current treatment with anti-viral therapy for HBV.
  • Treatment with investigational therapy within 42 days prior to initiation of study treatment
  • Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies.
  • Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 [IL-2]) within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment.
  • Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF-α agents) within 2 weeks prior to initiation of study treatment or anticipation of need for systemic immunosuppressive medication during study treatment, with the following exceptions:
    • Patients who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) may be eligible for the study after Medical Monitor approval has been obtained;
    • Patients who received mineralocorticoids (e.g., fludrocortisone), corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the study..
  • History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins.
  • Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab formulation.
  • Known allergy or hypersensitivity to any component of the chemotherapy regimen the patient will be assigned to.
  • For patients intended to receive cisplatin, any significant hearing impairment per the investigator’s clinical judgement.
  • Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within 5 months after last dose of atezolizumab, 30 days after the last dose of nab-paclitaxel, or 6 months after last dose of pemetrexed, gemcitabine, carboplatin, or cisplatin.
    • Women of childbearing potential must have a negative serum pregnancy test result within 14 days prior to initiation of study treatment.
Biologic/Vaccine, Drug, Administration of antineoplastic agent, Drug therapy
Cancer, Lung cancer, Non-small cell lung cancer
Atezolizumab, Biological therapy for cancer, Cancer treatment, Chemotherapy, Medical Oncology, Non-small cell lung cancer, Respiratory system, atezolizumab
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ANBL1531, A Phase 3 Study of 131I-Metaiodobenzylguanidine (131I-MIBG) or ALK Inhibitor Therapy Added to Intensive Therapy for Children With Newly Diagnosed High-Risk Neuroblastoma (NBL) (ANBL1531)

Iobenguane I-131 or Crizotinib and Standard Therapy in Treating Younger Patients With Newly-Diagnosed High-Risk Neuroblastoma or Ganglioneuroblastoma

Wendy Allen-Rhoades
All
365 days to 30 years old
Phase 3
This study is NOT accepting healthy volunteers
0000-100767-P01-RST
18-007616
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Inclusion Criteria:

  • Patients must be enrolled on ANBL00B1 or APEC14B1 prior to enrollment on ANBL1531.
  • Patients must have a diagnosis of neuroblastoma or ganglioneuroblastoma (nodular) verified by tumor pathology analysis or demonstration of clumps of tumor cells in bone marrow with elevated urinary catecholamine metabolites; the following disease groups are eligible:
    • Patients with International Neuroblastoma Risk Group (INRG) stage M disease are eligible if found to have either of the following features:
    • MYCN amplification (> 4-fold increase in MYCN signals as compared to reference signals), regardless of additional biologic features; OR
    • Age > 547 days regardless of biologic features.
  • Patients with INRG stage MS disease with MYCN amplification.
  • Patients with INRG stage L2 disease with MYCN amplification.
  • Patients > 547 days of age initially diagnosed with INRG stage L1, L2 or MS disease who progressed to stage M without prior chemotherapy may enroll within 4 weeks of progression to stage M.
  • Patients ≥ 365 days of age initially diagnosed with MYCN amplified INRG stage L1 disease who progress to stage M without systemic therapy may enroll within 4 weeks of progression to stage M.
  • Patients initially recognized to have high-risk disease must have had no prior systemic therapy (other than topotecan/cyclophosphamide initiated on an emergent basis and within allowed timing); patients observed or treated with a single cycle of chemotherapy per a low or intermediate risk neuroblastoma regimen (e.g., as per ANBL0531, ANBL1232 or similar) for what initially appeared to be non-high risk disease but subsequently found to meet the criteria will also be eligible; patients who receive localized emergency radiation to sites of life-threatening or function-threatening disease prior to or immediately after establishment of the definitive diagnosis will be eligible.
  • Creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥ 70 mL/min/1.73 m^2 or a serum creatinine based on age/sex as follows:
    • 1 to < 2 years: male = 0.6; female = 0.6;
    • 2 to < 6 years: male = 0.8; female = 0.8;
    • 6 to < 10 years: male = 1; female = 1;
    • 10 to < 13 years: male = 1.2; female = 1.2;
    • 13 to < 16 years: male = 1.5; female = 1.4;
    •  ≥ 16 years: male = 1.7; female = 1.4;
    • Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age; and
    • Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 10 x ULN; for the purposes of this study, ULN for SGPT (ALT) is 45.
  • Shortening fraction of ≥ 27% by echocardiogram, or ejection fraction of > 50% by echocardiogram or radionuclide angiogram.
  • No known contraindication to peripheral blood stem cell (PBSC) collection; examples of contraindications might be a weight or size less than the collecting institution finds feasible, or a physical condition that would limit the ability of the child to undergo apheresis catheter placement (if necessary) and/or the apheresis procedure.


Exclusion Criteria:

  • Patients with INRG stage L2 tumors without amplification of MYCN regardless of tumor histology (may meet criteria for high risk classification but are not eligible for this trial).
  • Patients with bone marrow failure syndromesm.
  • Patients for whom targeted radiopharmaceutical therapy would be contraindicated due to underlying medical disorders.
  • Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs; a pregnancy test is required for female patients of childbearing potential. 
  • Lactating females who plan to breastfeed their infants.
  • Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation.
Drug, Biologic/Vaccine, Procedure/Surgery
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MMRC-085: Myeloma-Developing Regimens Using Genomics (MyDRUG) (Genomics Guided Multi-arm Trial of Targeted Agents Alone or in Combination With a Backbone Regimen) (MyDRUG)

A Study to Evaluate Myeloma-Developing Regimens Using Genomics (MyDRUG)

Shaji Kumar
All
18 years and over
Phase 1/2
This study is NOT accepting healthy volunteers
0000-100769-P01-RST
18-011750
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Inclusion Criteria:
 

  • Have enrolled in the MMRF002 Molecular Profiling Protocol (NCT02884102) “companion’ protocol and have a report that is less than 120 days.
  • ≥ 18 years of age.
  • Willing to consent to the assigned Sub-Protocol.
  • Patient meets all entry criteria for the assigned Sub-Protocol.
  • High risk patients with relapsed refractory multiple myeloma (RRMM), who have:
    • received at least one prior but no more than 3 prior therapies;
    • exposed to both a PI and an IMiD;
    • had early relapse after initial treatment. Early relapse is defined by at least one of the following: (Relapse is defined as the IMWG uniform response criteria (Kumar et al, 2016);
    • Within 3 years of initiation of induction chemotherapy for post ASCT followed by maintenance, or 18 months if unmaintained after ASCT;
    • Within 18 months of initial non-ASCT based therapy.
  • Patients must have progressed after their most recent treatment and require therapy for myeloma.
  • The following laboratory values obtained ≤ 14 days prior to registration:
    • ANC ≥ 1000/ul;
    • Hgb ≥ 8 g/dl;
    • PLT ≥ 75,000/ul (Platelet transfusions to help patients meet eligibility criteria are not allowed within 3 days prior to study drug dosing for any dosing day);
    • Total bilirubin < 1.5 x upper limit of normal (ULN) or if total bilirubin is > 1.5 x ULN, the direct bilirubin must be ≤ 2.0 mg/dL;
    • AST < 3 x ULN;
    • Creatinine Clearance ≥ 30 mL/min by Cockroft Gault Equation.
  • Measurable disease of MM as defined by at least ONE of the following:
    • Serum monoclonal protein ≥ 0.5g by protein electrophoresis;
    • ≥ 200 mg of monoclonal protein in the urine on 24-hour electrophoresis;
    • Serum immunoglobulin FLC ≥10 mg/dL AND abnormal serum immunoglobulin kappa to lambda FLC ratio;
    • Monoclonal bone marrow plasmacytosis ≥30% (evaluable disease).
  • Eastern Cooperative Oncology Group (ECOG) Performance Status 0, 1, or 2.
  • Willingness to return to enrolling institution for follow-up.
  • Disease free of prior malignancies for ≥ 3 year with exception of currently treated basal cell, squamous cell carcinoma of the skin, carcinoma “insitu” of the cervix or breast, or prostate cancer not requiring therapy.
  • Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to ASA may use warfarin or low molecular weight heparin).
  • All study participants must be willing to be registered into the mandatory pomalidomide (POMALYST®) Risk Evaluation and Mitigation Strategy (REMS®) program and be willing and able to comply with the requirements of the POMALYST REMS® program.
  • Females of reproductive potential* must be willing to adhere to the scheduled pregnancy testing as required in the POMALYST REMS® program.
  • Ability to understand the purpose and risks of the study and provide signed and dated informed consent form (ICF) and authorization to use protected health information.

*Female of reproductive potential is any sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy, or 2) has not been naturally postmenopausal (not having menstrual cycles due to cancer therapy does not rule out childbearing potential) for at least 24 consecutive months.

Drug, Drug therapy
Cancer, Multiple myeloma, Plasma cell disorders
Cancer treatment, Hematopoietic system, Immune system, Medical Oncology, Relapse multiple myeloma
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EA6174, STAMP: Surgically Treated Adjuvant Merkel Cell Carcinoma with Pembrolizumab, a Phase III Trial

A Study to Evaluate Pembrolizumab for Surgically Treated Adjuvant Merkel Cell Carcinoma

Svetomir Markovic
All
18 years and over
Phase 3
This study is NOT accepting healthy volunteers
0000-100770-P01-RST
18-010460
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Inclusion Criteria:
 

  • Age ≥ 18 years.
  • Patients must have an ECOG performance Status: 0, 1, or 2; however, those patients with a performance state of 3 because they are wheel chair bound due to congenital or traumatic events more than one year before the diagnosis of Merkel cell carcinoma are eligible).
  • Women must not be pregnant or breast-feeding due to the unknown effects of the study drug in this setting.
  • All women of childbearing potential must have a blood test or urine study within 2 weeks 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).
      • Female of child bearing potential? ______ (Yes or No)
      • Date of blood test or urine study: ___________
  • Women of childbearing potential and sexually active males on Arm A MK-3475 (Pembrolizumab) must use accepted and effective method(s) of contraception or abstain from sex from time of registration, while on study treatment, and continue for 120 days after the last dose of study treatment. For patients on Arm B only receiving radiation therapy, contraception use should be per  institutional standard.
  • Patient must have a histological confirmation of diagnosis of Merkel cell carcinoma (MCC), pathologic stages (AJCC version 8) I-IIIb:
    • Stage I patients with negative sentinel lymph node biopsy are ineligible;
    • Patients who have a positive biopsy or for whom no biopsy was done are eligible;
    • Patients with distant metastatic disease (stage IV) are not eligible;
    • The primary tumor must have grossly negative margins. (Microscopically positive margins are allowed);
    • Cancers of unknown primary that have regional disease only can be included;
    • Complete nodal dissection is not required for eligibility.
  • Patients with all macroscopic Merkel cell carcinoma (either identified by physical exam or imaging) have been completely resected by surgery within 16 weeks before registration.
  • All patients must have disease-free status documented by a complete physical examination and conventional imaging studies within 8 weeks prior to registration.
  • Patient must have the following required values for initial laboratory tests obtained within 4 weeks prior to registration:
    • White Blood Count ≥ 2000/uL:
      • WBC: __________ Date Obtained: __________
    • Absolute neutrophil count (ANC) ≥ 1000/uL:
      • ANC: __________ Date Obtained: __________
    • Platelets ≥ 75 x 103/uL:
      • Platelet: __________ Date Obtained: __________
    • Hemoglobin ≥ 8 g/dL (≥ 80 g/L; may be transfused):
      • Hemoglobin: __________Date Obtained: __________
    • Creatinine ≤ 2.0 x ULN:
      • Creatinine: __________ Institutional ULN : __________
    • AST and ALT ≤ 2.5 x ULN:
      • AST: _______ Institutional ULN: _________
      • Date Obtained: ________________________
      • ALT: _______ Institutional ULN: _________
      • Date Obtained: ________________________
    • Total Bilirubin ≤ 2.0 x ULN, (except patients with Gilbert's Syndrome, who must have a total bilirubin less than 3.0 mg/dL)
      • Bilirubin: __________ Institutional ULN: _____________
      • Date Obtained:____________________________
  • Patients who are HIV+ with undetectable HIV viral load are eligible provided they meet all other protocol criteria for participation.
  • Patients with HBV or HCV infection are eligible provided viral loads are undetectable.
  • Patients on suppressive therapy are eligible.
  • Patients must not be on active immunosuppression, have a history of life threating virus, have had other (beside non-melanoma skin cancers, or recent indolent cancers e.g.: resected low grade prostate cancer) invasive cancer diagnoses in the last two years, or have had immunotherapy of any kind within the last 2 years.
  • Operative notes from patient’s surgical resection must be accessible.


Exclusion Criteria:

  • Patient may not have a history of distant metastatic disease.
    • NOTE: loco-regional recurrent disease is acceptable, as long as this is not metastatic (prior surgery with or without radiation therapy is acceptable).
  • For patients with initial presentation of Merkel cell carcinoma, patient must have no previous systemic therapy or radiation therapy prior to surgery for Merkel cell carcinoma and cannot have completed adjuvant radiation therapy for Merkel Cell Carcinoma more than 6 weeks prior to registration. Patients actively undergoing radiation therapy or having completed adjuvant radiation therapy within 6 weeks of registration are eligible, as long as resection date is within 16 weeks of registration.
  • Patients must not have a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
  •  
Biologic/Vaccine, Other, Radiation, Administration of antineoplastic agent, Drug therapy, Immunotherapy for cancer
Cancer, Merkel cell carcinoma, Non-melanoma skin cancer, Skin cancer
Biological therapy for cancer, Cancer treatment, Integumentary system, Medical Oncology, Merkel cell carcinoma, Pembrolizumab [USAN:INN], pembrolizumab
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AL3818-US-004, A Phase III Study of AL3818 (Catequentinib, Anlotinib) Hydrochloride Monotherapy in Subjects With Metastatic or Advanced Alveolar Soft Part Sarcoma, Leiomyosarcoma and Synovial Sarcoma (APROMISS)

A Study of Catequentinib, Anlotinib in Metastatic or Advanced Alveolar Soft Part Sarcoma, Leiomyosarcoma and Synovial Sarcoma

Brittany Siontis
All
18 years and over
Phase 3
This study is NOT accepting healthy volunteers
0000-100778-P01-RST
18-011002
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Inclusion Criteria:

  • Written informed consent provided before any study-specific procedures are initiated. Subject must be able to understand and be willing to sign a written informed consent form.
  • Male or female at least 18 years of age.
  • Indication A – ASPS:
    • Histologically proven, unresectable, locally advanced or metastatic alveolar soft part sarcoma;
    • Indication B – LMS: Histologically proven, unresectable, recurrent, locally advanced or metastatic leiomyosarcoma (of soft tissue, cutaneous origin, vascular origin and of the bone). (New Recruitment Suspended);
    • Indication C – SS: Histologically proven, unresectable, recurrent, locally advanced or metastatic synovial sarcoma;
    • Indication D – LMS: Histologically proven, unresectable, recurrent, locally advanced or metastatic leiomyosarcoma (of soft tissue, cutaneous origin, and vascular origin).
  • Indication A – ASPS:
    • Subjects with or without prior therapy.
  • Indications B – LMS:
    • Subjects previously treated with at least one prior line of approved therapy. (New Recruitment Suspended).
  • Indication C – SS:
    • Subjects previously treated with at least one prior line of standard systemic therapy, including first-line anthracycline containing regimen (except if medically contraindicated or refused by subject).
  • Indication D – LMS:
    • Treatment of patients with metastatic or advanced leiomyosarcoma (LMS) who have failed at least one prior line of standard therapy and are ineligible for or refuse standard second-line therapy or are suitable for third- and further-line treatment. Patients must have received and progressed on prior therapy and have been treated any line with an anthracycline.
  • Show clinical or objective disease progression after the last administration of the last standard therapy or have stopped standard therapy due to intolerability within 6 months of enrollment (excluding ASPS subjects who have not received prior therapy).
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Has measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 confirmed by CT or MRI scan of the chest, abdomen and pelvis (and other areas of disease) within 28 days prior to enrollment.
  • Life expectancy of at least 3 months.
  • Females of childbearing potential must have a negative pregnancy test (by serum betaHCG) within 7 days prior to the start of treatment.
  • Female of childbearing potential must be surgically sterile (have had a hysterectomy or bilateral oophorectomy, tubal ligation), abstinent (at the discretion of the investigator), or agree to use adequate contraception since signing of the informed consent form until at least 3 months after the last study drug administration. Females of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 2 years. Males must agree to use adequate contraception since signing of the informed consent form until at least 3 months after the last study drug administration. Adequate contraception is defined in the study as any medically recommended method (or combination of methods) at the discretion of the investigator.
  • Adequate hematologic, hepatic and renal function as assessed by the following laboratory requirements conducted within 28 days of enrollment:
    • Total bilirubin ≤ the upper limit of normal (ULN), unless the patient has documented Gilbert’s disease for which the total bilirubin should be ≤ 3;
    • Alanine aminotransferase and aspartate aminotransferase ≤ 2.5 of the ULN (≤ 5 x of ULN for subjects with liver involvement of their cancer);
    • Amylase and lipase ≤ 1.5 x of ULN;
    • Serum creatinine ≤ 1.5 x of ULN;
    • Glomerular filtration rate > 30ml/min/1.73 m^2 according to the Modified Diet in Renal Disease abbreviated formula or creatinine clearance (CrCL) ≥ 60 ml/min (Cockcroft and Gault) or by 24 hour urine collection;
    • International normalize ratio (INR) and the activated partial thromboplastin time (aPTT/PTT) ≤ 1.5 x ULN. (Subjects who are therapeutically treated with an agent such LMWH or heparin will be allowed to participate provided that no prior evidence of an underlying abnormality in coagulation parameters exists);
    • Platelet count ≥ 100,000 cells/mm^3, hemoglobin ≥ 9 g/dL, absolute neutrophil count ≥ 1,500 cells/mm^3.
    • Alkaline phosphatase limit ≤ 2.5 x ULN (< 5 x ULN for subjects with liver involvement of their cancer).
    • Urine protein ≤ 30 mg/dL.  If urine protein is ≥ 30 mg/dL, a 24-hour urine collection will be required and most show total protein excretion ≤ 1,000 mg per 24 hours or spot urine protein (mg/dL) to creatinine (mg/dL) ratio must be ≤ 1.0.
  • Left ventricular ejection fraction (LVEF) of ≥ 50% by ECHO or MUGA within 56 days of enrollment.
  • Two readings of systolic blood pressure ≤ 140 mm Hg and diastolic blood pressure ≤ 90 mm Hg at screening taken at least 5 minutes apart in the sitting position after 5 minutes of rest. Subjects with well managed hypertension who are on oral antihypertensives must be on their current medication(s) and stable dose(s) for at least 2 weeks prior to enrollment.


Exclusion Criteria:

  • Prior treatment with or have known hypersensitivity to AL3818.
  • Indication A – ASPS:
    • Prior treatment with cediranib.
  • Indication B – LMS:
    • Prior treatment with or have known hypersensitivity to dacarbazine. (New Recruitment Suspended).
  • Indication C – SS:
    • Prior treatment with or have known hypersensitivity to dacarbazine.
  • Indication D – LMS:
    • Prior treatment with anlotinib.
  • Previous or concurrent cancer that is distinct in primary site or histology from ASPS, LMS, or SS within 5 years before enrollment except for successfully treated in situ carcinoma, non-melanoma skin cancer and superficial bladder tumors (Ta, Tis and T1).
  • Received last dose of systemic cytotoxic therapy or investigational therapy within 21 days of enrollment or last dose of hormonal therapy, immunotherapy, targeted therapy or any other type of non-cytotoxic anti-cancer therapy within 14 days of enrollment.
  • Prior treatment with extended-field radiotherapy (EFRT) within 28 days of enrollment or prior treatment with any other form of radiotherapy within 14 days of enrollment.
  • Known active CNS metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided that they are stable with no evidence of progression by imaging, and all neurologic symptoms have returned to baseline, and should not be using corticosteroids for at least 7 days prior to study treatment.
  • Cavitary tumors or tumors invading or abutting large blood vessels in the thorax.
  • History of gastrointestinal perforation, abdominal fistula or intra-abdominal abscess within 6 months of enrollment.
  • Known history of bleeding disorders (e.g., von Willebrand disease or hemophilia).
  • Clinically significant bleeding such as gross hematuria, gastrointestinal bleeding and hemoptysis within 6 months prior to enrollment.
  • CTCAE version 4.03 > grade 2 pulmonary hemorrhage or ≥ grade 3 of other forms of bleeding within 28 days prior to enrollment.
  • History of untreated deep venous thrombosis (DVT) within the past 6 months. Patients with recent DVT who are treated with therapeutic anti-coagulating agents (excluding therapeutic warfarin which is exclusionary) for at least 14 days prior to start of study treatment.
  • Use of aspirin (> 325 mg/day) within 10 days prior to the first dose of study treatment. The use of prophylactic therapeutic anti-coagulants are allowed provided that INR or aPTT are within therapeutic limits (according to the medical standard of the enrollment institution) and patient has been on a stable dose of anticoagulants for at least two weeks prior to the first dose of study treatment.
  • Serious non-healing wound, active ulcer.
  • Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to enrollment or minor surgical procedure within 7 days of enrollment.
  • CTCAE version 4.03 ≥ grade 3 peripheral neuropathy.
  • Any unrecovered toxicity reactions of CTCAE version 4.03 ≥ grade 1 caused by any previous therapy (excluding alopecia and neurotoxicity ≤ grade 2).
  • QTcF ≥ 470 msec (per Fridericia’s formula) on electrocardiogram within 28 days of enrollment.
  • Severe and uncontrolled disease, including:
    • Class I and above myocardial ischemia or myocardial infarction, cardiac arrhythmia and Class 2 or above congestive heart failure classified according to New York Heart Association (NYHA);
    • Active or failed to control serious infections (CTCAE version 4.03 ≥ grade 2 infections);
    • Liver disease such as cirrhosis of the liver, decompensated liver disease, chronic active hepatitis needing anti-viral therapy;
    • Renal failure needing hemodialysis or peritoneal dialysis;
    • Poorly controlled diabetes (HgA1C ≥ 8);
    • Untreated and uncontrolled epileptic seizures;
    • History of psychotropic drug abuse and inability to quit;
    • Untreated psychiatric disorders.
  • Known HIV-positive.
  • Had organ transplantation.
  • Clinical conditions affecting the intake and use of oral medications (e.g., inability to swallow, chronic diarrhea, and intestinal obstruction).
Drug, Administration of antineoplastic agent, Drug therapy
Cancer, Leiomyosarcoma, Sarcoma, Soft tissue sarcoma, Synovial sarcoma
Alveolar soft part sarcoma, Anlotinib, Cancer treatment, Chemotherapy, Dacarbazine, Leiomyosarcoma, Medical Oncology, Musculoskeletal system, Synovial sarcoma, dacarbazine
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Phase II Trial to Evaluate Immune-related Biomarkers for Pathological Response in Stage II-III HER2-positive Breast Cancer Receiving Neoadjuvant Chemotherapy with Subsequent Randomization to Multi-epitope HER2 Vaccine vs. Placebo in Patients with Residual Disease Post-neoadjuvant Chemotherapy

A Study to Evaluate Immune-related Biomarkers for Pathological Response in Stage II-III HER2-positive Breast Cancer

Kathryn Ruddy
Female
18 years and over
Phase 2
This study is NOT accepting healthy volunteers
0000-100782-P01-RST
18-009483
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Pre-Registration Inclusion Criteria for All Patients (include Safety Lead-In) :

  • Female age ≥ 18 years.
  • Histologically confirmed adenocarcinoma of the breast stage ≥ T2 OR ≥ N1 based on the 7th edition of TNM staging system from the American Joint Committee on Cancer.
  • Any ER or PR but HER2 positive defined as 3+ staining intensity (on a scale of 0 to 3) by means of IHC analysis OR gene amplification on fluorescence in situ hybridization (FISH) ratio ≥ 2.0.
  • Patients must have adequate pretreatment biopsy sample available.
    • NOTE: Adequate tissue samples defined as core needle biopsy or incisional biopsy or excisional samples that can provide ≥ 3 core needle biopsies with at least 14G needle with 12 unstained sections of 5 micron thickness. Fine needle aspiration (FNA) sample alone is not sufficient.
    • NOTE: Patients without adequate pretreatment biopsy samples must be agreeable to have an additional research biopsy prior to neoadjuvant therapy.
  • ECOG Performance Status (PS) 0, 1, 2.
  • Willing to employ adequate contraception from the time of pre-registration through 6 months after the final vaccine cycle.
  • Willing to receive a tetanus vaccination if subject has not had one <1 year prior to pre-registration.
  • Provide written informed consent.
  • Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study).
  • Willing to provide mandatory tissue and blood samples for correlative research purposes.
  • Negative pregnancy test done ≤ 7 days prior to pre-registration, for persons of childbearing potential only.
    • NOTE: If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.

Pre-Registration – Exclusion Criteria for all patients (include Safety Lead-In):

  • Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:
    • Pregnant person;
    • Nursing person unwilling to stop breast feeding;
    • Person of child bearing potential who are unwilling to employ adequate contraception from the time of registration through 6 months after the final vaccine cycle.
  • Clinical evidence of local recurrence or distant metastases.
    • NOTE: All patients must have either a PET/CT or CT chest, abdomen, and pelvis with bone scan to rule out distant metastases ≤ 90 days prior to pre-registration. If any of these is concerning, follow-up imaging or biopsy should be performed if indicated rule out distant metastases.
  • 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.
  • Immunocompromised patients including patients known to be HIV positive or those on chronic steroids.
    • NOTE: Must be off systemic steroids at least 14 days prior to pre-registration; however, topical steroids, inhalants or steroid eye drops are permitted.
  • 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 situations that would limit compliance with study requirements.
  • Uncontrolled acute or chronic medical conditions including, but not limited to the following:
    • Active infection requiring antibiotics;
    • Congestive heart failure with New York Heart Association class III or IV; moderate to severe objective evidence of cardiovascular disease;
    • Myocardial infarction or stroke < 6 months prior to pre-registration;
    • Significant cardiac arrhythmia or unstable angina.
  • Receiving any other investigational agent.
  • Other active malignancy at time of pre-registration or < 3 years prior to pre-registration.
    • EXCEPTIONS: Non-melanoma skin cancer or carcinoma-in-situ (e.g., of cervix, prostate).
    • NOTE: If there is a history of prior malignancy, they must not be receiving other specific treatment (cytotoxics, monoclonal antibodies, small molecule inhibitors) for their cancer.
  • Known history of autoimmune disease, including Type I diabetes.
  • Any prior hypersensitivity or adverse reaction to GM-CSF.
  • History of trastuzumab-related cardiac toxicity requiring interruption or discontinuation of therapy, even if LVEF fully recovered.
  • Baseline LVEF <50%.
  • Failure to fully recover from acute, reversible effects of prior chemotherapy regardless of interval since last treatment.
  • History of myocardial infarction ≤ 168 days (6 months) prior to pre-registration, or congestive heart failure requiring use of ongoing maintenance therapy for life threatening ventricular arrhythmias.
  • Patients who received tamoxifen or raloxifene or another agent for prevention of breast cancer ≤ 2 months prior to pre- registration.

Registration – Inclusion Criteria (Safety Lead-In):

  • The following laboratory values obtained ≤ 28 days prior to registration:
    • Absolute neutrophil count (ANC) ≥ 1500/mm^3;
    • Platelet count ≥ 75,000/mm^3;
    • Hemoglobin ≥ 9.0 g/dL;
    • Direct bilirubin < 1.5 x upper limit of normal (ULN);
    • Aspartate transaminase (AST) ≤ 3 x ULN;
    • Creatinine ≤ 2 X ULN;
    • • PT/INR/PTT ≤ 1.5 X ULN OR if patient is receiving anticoagulant therapy and PT or PTT is within therapeutic range of intended use of coagulant.
  • Completed planned curative breast surgeries (not including any future breast reconstructive surgery) and any radiation therapy ≥ 30 days prior toregistration.
  • Completed last cycle of chemotherapy ≥ 90 days prior toregistration.
    • NOTE: Prior to randomization, patients must not receive ≥ 6 cycles of T-DM1 maintenance therapy after surgery.
  • Have residual disease with ≥ 1 cm residual tumor in the breast (≥ ypT1c) and/or persistent lymph node positivity after trastuzumab ± pertuzumab based neoadjuvant chemotherapy.
  • Adequate tissue specimens from both pre-treatment biopsy and surgery must be submitted. Adequate tissue samples defined as core needle biopsy or incisional biopsy or excisional samples that can provide ≥ 3 core needle biopsies with at least 14G needle with 12 unstained sections of 5 micron thickness.
    • NOTE: Fine needle aspiration (FNA) sample alone is not sufficient.
  • Negative pregnancy test done ≤7 days prior toregistration, for persons of childbearing potential only.
    • NOTE: If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  • ECOG Performance Status (PS) 0, 1, 2.
  • Willing to employ adequate contraception from the time of registration through 6 months after the final vaccine cycle.

Registration – Exclusion Criteria (Safety Lead In):

  • *No exclusion criteria for registration.

Registration – Inclusion Criteria for Patients with No Residual Disease (pCR)- (PHASE II):

  • ECOG Performance Status (PS) 0, 1, 2.
  • The following laboratory values obtained ≤ 28 days prior to registration:
    • Absolute neutrophil count (ANC) ≥ 1500/mm^3;
    • Platelet count ≥ 75,000/mm^3;
    • Hemoglobin ≥ 9.0 g/dL;
    • Direct bilirubin < 1.5 x upper limit of normal (ULN);
    • Aspartate transaminase (AST) ≤ 3 x ULN;
    • Calculated serum creatinine clearance of ≥ 50 mL/min.
    • PT/INR/PTT ≤ 1.5 X ULN OR if patient is receiving anticoagulant therapy and PT or PTT is within therapeutic range of intended use of coagulants.
  • Negative pregnancy test done ≤ 7 days prior to registration, for person of childbearing potential only.
    • NOTE: If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.

Registration – Exclusion Criteria for Patients with no residual disease (pCR)- (PHASE II)

  • *No exclusion criteria for registration.

Randomization – Inclusion Criteria for Patients with Residual Disease Post Neoadjuvant Tratuzumab ± Pertuzumab-based Chemotherapy (no PCR)- (PHASE II):

  • The following laboratory values obtained ≤ 28 days prior to randomization.
    • Absolute neutrophil count (ANC) ≥ 1500/mm3;
    • Platelet count ≥ 75,000/mm3;
    • Hemoglobin ≥ 9.0 g/dL;
    • Direct bilirubin < 1.5 x upper limit of normal (ULN);
    • Aspartate transaminase (AST) ≤ 3 x ULN;
    • Creatinine ≤ 2 X ULN;
    • PT/INR/PTT ≤ 1.5 X ULN OR if patient is receiving anticoagulant therapy and PT or PTT is within therapeutic range of intended use of coagulant.
  • Completed planned curative breast surgeries (not including any future breast reconstructive surgery) and any radiation therapy ≥ 30 days prior to randomization.
  • Completed last cycle of chemotherapy ≥ 90 days prior to randomization.
    • NOTE: Prior to randomization, patients must not receive ≥ 6 cycles of T-DM1 maintenance therapy after surgery.
  • Have residual disease with ≥ 1 cm residual tumor in the breast (≥ ypT1c) and/or persistent lymph node positivity after trastuzumab ± pertuzumab based neoadjuvant chemotherapy.

* Part of the Active Monitoring Phase of a study. Participants will be required to return to the consenting site for follow-up. Booster vaccinations will occur at 3 and 12 months post completion of the 6 cycles of vaccinations and maintainence TDM-1.

Biologic/Vaccine, Drug, Other
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S1706; A Phase II Randomized Trial of Olaparib (NSC-747856) Administered Concurrently With Radiotherapy Versus Radiotherapy Alone for Inflammatory Breast Cancer

A Study to Compare Administering Olaparib Concurrently With Radiotherapy vs. Radiotherapy Alone in Treating Patients With Inflammatory Breast Cancer

Dean Shumway
All
18 years and over
Phase 2
This study is NOT accepting healthy volunteers
0000-100787-P01-RST
19-000062
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Inclusion Criteria:

  • Patients must have inflammatory breast cancer without distant metastases. All biomarker subtype groups (estrogen receptor [ER], progesterone receptor [PR], HER2) are eligible. Inflammatory disease will be defined per American Joint Committee on Cancer (AJCC) 8th edition with documentation by history/exam and pathology at the time of diagnosis. 
  • All patients must have completed neoadjuvant chemotherapy prior to mastectomy. The chemotherapy regimen is at the discretion of the treating physician but it is recommended that it include at least 4 cycles of anthracycline and/or taxane-based therapy (plus targeted therapy for patients with HER2+ disease). Response to chemotherapy is not a criterion for eligibility (both complete responders and those with residual disease are eligible). Please note that although pathologic complete response (pCR) is not required or excluded, pCR status must be determined post-surgery prior to randomization.
  • All patients must have undergone modified radical mastectomy (with negative margins on ink) with pathologic nodal evaluation (from level I and II axillary lymph node dissection) at least 3 weeks and no more than 12 weeks prior to randomization, unless they receive additional chemotherapy after mastectomy. Patients must not have gross residual tumor or positive microscopic margins after mastectomy. 
  • Additional adjuvant chemotherapy after surgery is allowed at the discretion of the treating physician, either completed prior to randomization or planned for after completion of protocol treatment. If adjuvant chemotherapy is administered after mastectomy, the patient must be randomized at least 3 weeks but no more than 12 weeks after the last dose of adjuvant chemotherapy. 
  • Patients must not have a history of radiation therapy to the ipsilateral chest wall and/or regional nodes. Prior radiation therapy to other body sites is allowed.
  • Patients must not be planning to receive any other investigational agents during radiation therapy. Prior therapy, including prior treatment with olaparib or other PARP inhibitor, is allowed. 
  • Patients must not have a known hypersensitivity to olaparib or any of the excipients of the product.
  • Patients must not have unresolved or unstable grade 3 or greater toxicity from prior administration of another investigational drug and/or prior anti-cancer treatment. 
  • Patients must not be planning to receive strong or moderate CYP3A inhibitors or inducers while on olaparib treatment. Patients receiving strong or moderate CYP3A inhibitors must agree to discontinue use at least 2 weeks prior to receiving olaparib. Patients receiving strong or moderate CYP3A inducers must agree to discontinue use at least 5 weeks prior to receiving olaparib. 
  • Patients must not be planning to receive live virus or live bacterial vaccines while receiving olaparib and during the 30 day follow up period.
  • Patients must not be planning to receive any additional anti-cancer therapy (chemotherapy, endocrine therapy, immunotherapy, biological therapy or other novel agent) while receiving radiotherapy with or without study medication. If a patient is receiving concurrent anti-HER2 targeted therapies, they must not take these medications during the period of radiotherapy (with or without study drug) while enrolled on the study. 
  • Patients must be ≥ 18 years of age.
  • Patients must have Zubrod performance status 0-2. 
  • Patients must have adequate hematologic function as evidenced by all of the following within 28 days prior to registration:
    • Absolute neutrophil count (ANC) >= 1000/mm^3 (within 28 days prior to registration);
    • Platelet count >= 100,000/mm^3 (within 28 days prior to registration);
    • Hemoglobin >= 9.0 g/dL (after transfusion if required and within 28 days prior to registration).
  • Patients must have adequate renal function as evidenced by calculated creatinine clearance >= 51 mL/min by Cockcroft-Gault equation, within 28 days prior to registration.
  • Calculated creatinine clearance = [(140
    •age) x wt (kg) x 0.85 (if female)]/[72 x creatinine (mg/dl)].
  • Patients must have adequate hepatic function as evidenced by all of the following within 28 days prior to registration:  
    • Total bilirubin =< 1.5 x upper limit of normal (ULN) (within 28 days prior to registration).
    • Patients with documented Gilbert's disease may have bilirubin up to 2.5 mg/dL.
    • Serum glutamic-oxaloacetic transaminase (SGOT) =< 2.5 x ULN (within 28 days prior to registration).
    • Serum glutamate pyruvate transaminase (SGPT) =< 2.5 x ULN (within 28 days prior to registration) .
    • Alkaline phosphatase =< 2.5 x ULN (within 28 days prior to registration). 
  • Patients must not have a history of other prior malignancy 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 five years.
  • Female patients must be postmenopausal or have a negative urine or serum pregnancy test within 28 days prior to registration. Female patients of childbearing potential and male patients with partners of childbearing potential, who are sexually active, must agree to the use of two highly effective forms of contraception. 
  • Patients who are breastfeeding must agree to discontinue breastfeeding before receiving olaparib due to potential risk for adverse events in nursing infants secondary to treatment of the mother with olaparib. 
  • Patients must not have active uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris or cardiac arrhythmia. 
  • Patients must be able to swallow and retain oral medications and have no known gastrointestinal disorders likely to interfere with absorption of the study medication. 
  • Patients must not have a history of a resting electrocardiography (ECG) indicating uncontrolled, potentially reversible cardiac conditions (such as unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, Fridericia's formula corrected QT interval [QTcF] prolongation > 500 ms, electrolyte disturbances) or congenital long QCYP3T syndrome. 
  • Patients must not have myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or with features suggestive of MDS/AML. 
  • Patient must not have had major surgery within 2 weeks of starting study treatments and patients must have recovered from any effects of any major surgery. 
  • Patients must not have a history of uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, or extensive interstitial bilateral lung disease on high resolution computed tomography (HRCT) scan. 
  • Patients must not have had previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT). 
  • Patients must not have had whole blood transfusions in the last 120 days prior to randomization.
Drug, Radiation, Administration of antineoplastic agent, Chemotherapy, Drug therapy, Radiation therapy procedure or service
Breast cancer, Cancer, Inflammatory breast cancer
Cancer treatment, Chemotherapy, Chemotherapy for breast cancer, Inflammatory carcinoma of breast, Medical Oncology, Olaparib [USAN:INN], Radiation therapy, Radiation therapy for breast cancer, olaparib
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Phase III Randomized Trial of Standard Systemic Therapy (SST) Versus Standard Systemic Therapy Plus Definitive Treatment (Surgery or Radiation) of the Primary Tumor in Metastatic Prostate Cancer

A Study of Standard Systemic Therapy with or without Definitive Treatment in Treating Participants with Metastatic Prostate Cancer

Matthew Tollefson
Male
18 years and over
Phase 3
This study is NOT accepting healthy volunteers
0000-100794-P01-RST
19-000597
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Inclusion Criteria:
 

STEP 1 REGISTRATION
•DISEASE-RELATED CRITERIA

  • All patients must have a histologically or cytologically proven diagnosis of adenocarcinoma of the prostate. Patients with pure small cell carcinoma* (SCC), sarcomatoid, or squamous cell carcinoma are not eligible. (*morphology must be consistent with SCC; synaptophysin or chromogranin positive by immunohistochemical staining is insufficient to diagnose SCC).
  • Patients must have an intact prostate.
  • Patients must have at least one of the following scans performed, showing evidence of metastatic disease:
    • technetium bone scan; OR
    • CT of abdomen & pelvis; OR
    • MRI of pelvis..
  • Scans must be performed between 42 days prior to start of first hormonal therapy and 14 days following start of first hormonal therapy. Metastatic disease that is detected by PET scan only (NaF, PSMA, FACBC, C11) but not conventional imaging (Tc99 bone scan, CT or MRI) or solitary metastases by conventional imaging, must be confirmed histologically or cytologically.
  • Patients with known brain metastases are not eligible. Brain imaging studies are not required for eligibility if the patient has no neurologic signs or symptoms suggestive of brain metastasis. If brain imaging studies are performed, they must be negative for disease.

STEP 1 REGISTRATION
•PRIOR/CONCURRENT THERAPY CRITERIA

  • Patients must have received no more than 28 weeks of SST, as measured from the date of first hormonal therapy (LHRH agonist or LHRH antagonist) or surgical castration. SST is defined as current NCCN guidelines for metastatic prostate cancer.
  • No prior local therapy for prostate adenocarcinoma is allowed (e.g., brachytherapy, HIFU, cryotherapy, laser ablative therapies). Any prior therapy for benign conditions, such as obstruction, are acceptable (e.g., transurethral resection of the prostate, greenlight laser ablation, microwave ablation).
  • Patients must not have received any prior systemic therapy for prostate cancer, outside of line of SST to be used for duration of study.
  • Patients must not have progressed while on SST.
  • Patients with oligometastatic prostate cancer may receive metastasis directed therapy to up to four sites of disease prior to randomization.

STEP 1 REGISTRATION
•CLINICAL/LABORATORY CRITERIA:

  • Patients must be ≥ 18 years of age.
  • Patients must have a complete physical examination and medical history within 28 days prior to registration.
  • Patients must have a documented PSA:
    • Prior to initiation of SST;
    • Within 28 days prior to registration;
    • Any additional PSAs measured while receiving SST should be recorded.
  • Patients must have a testosterone lab documented within 28 days prior to registration. Any additional testosterone labs measured while receiving SST should be recorded as well as pretreatment initiation if available.
  • No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, adequately treated Stage 0, 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.

STEP 1 REGISTRATION
•SPECIMEN SUBMISSION CRITERIA

  • Patients must be offered the opportunity to participate in translational medicine studies and specimen banking for future studies.

STEP 1 REGISTRATION - QUALITY OF LIFE CRITERIA

  • Patients who can complete Patient-Reported Outcome instruments in English, Spanish or French, must participate in the quality of life studies.

STEP 1 REGISTRATION - REGULATORY CRITERIA

  • 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.

STEP 2 RANDOMIZATION
•DISEASE-RELATED CRITERIA

  • Patients must have no evidence of disease progression during the 28 weeks of SST, as shown by:
    • PSA measure;
    • imaging (bone scan and one of the following: CT of abdomen & pelvis, MRI of abdomen & pelvis, CT of abdomen & MRI of pelvis) within 42 days prior to randomization.
  • Patients must have no evidence of symptomatic deterioration (as defined by physician discretion) within 28 days prior to randomization.
  • Patients must have consultation with a urologist and have surgically resectable disease regardless of definitive treatment intent or randomization.

STEP 2 RANDOMIZATION - PRIOR/CONCURRENT THERAPY CRITERIA

  • Patients must have received at least 22 and no more than 28 weeks of SST, as measured from the date of first hormonal therapy (LHRH agonist or LHRH antagonist) or surgical castration. SST is defined by current NCCN guidelines for metastatic prostate cancer.
  • Patients must not be planning to receive docetaxel after randomization.
  • Any toxicities from SST must have resolved to ≤ Grade 1 (CTCAE Version 5.0) prior to randomization.
  • Patients may have received elective metastasis directed therapy to oligometastatic sites (≤ 4 sites). All treatment must be completed prior to randomization.

STEP 2 RANDOMIZATION - CLINICAL/LABORATORY CRITERIA

  • Patients must have a PSA performed within 28 days prior to randomization.
  • Patients must have a testosterone < 50 ng/dL within 28 days prior to randomization.
  • Patients must have a Zubrod performance status of 0 – 1 within 28 days prior to randomization.
Drug, Other, Procedure/Surgery, Radiation, Prostate destructive procedure, Radiation therapy procedure or service, Radiation oncology AND/OR radiotherapy
Cancer, Prostate cancer
Adenocarcinoma of prostate, Cancer treatment, Medical Oncology, Radiation therapy, Reproductive system
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MC1821 - Randomized Phase II Study of Standard Chemotherapy with Docetaxel with or without Bintrafusp Alfa in Patients with Advanced NSCLC after Progressing on a Combination of Anti-PD-1/PD-L1 Agents and Chemotherapy

A Study to Evaluate Docetaxel With or Without Bintrafusp Alfa to Treat Patients with Advanced Non-small Cell Lung Cancer

Alex Adjei
All
18 years and over
Phase 2
This study is NOT accepting healthy volunteers
0000-100797-P01-RST
19-010887
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Inclusion Criteria:

  • Age ≥ 18 years
  • Histological confirmation of non-small cell lung cancer (NSCLC) with advanced disease.
  • Prior treatment required:
  • Anti-PD1/PD-L1 agent in combination with platinum-based chemotherapy
  • NOTE: Tumor lesions in a previously irradiated area are not considered measurable disease; Disease that is measurable by physical examination only is not eligible.
  •  
  • ECOG Performance Status (PS) 0 or 1.
  • The following laboratory values obtained ≤ 14 days prior to registration:
  • Hemoglobin ≥ 9.0 g/dL
  • Absolute neutrophil count (ANC) ≥ 1500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Total bilirubin ≤ ULN
  • Alanine aminotransferase (ALT/SGPT) and aspartate transaminase (AST/SGOT) ≤ 1.5 × ULN
  • Alkaline phosphatase ≤ 2.5 × ULN
  • PT/INR/aPTT ≤1.5 × ULN OR if patient is receiving anticoagulant therapy INR or aPTT is within target range of therapy
    •  
  • Calculated creatinine clearance ≥ 30 ml/min using the Cockcroft-Gault formula.
  • Negative pregnancy test done ≤7 days prior to registration, for persons of childbearing potential only.
  • NOTE: If a urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  • Willing to use birth control as follows:
  • If able to become pregnant: Willing to use birth control during treatment and for 6 months after last dose of docetaxel and/or bintrafusp alfa, whichever is later.
  • If able to father a child: Willing to use birth control with partners able to become pregnant during treatment and for 3 months after last dose of docetaxel and/or bintrafusp alfa, whichever is later.
  • Provide written informed consent.
  • Willingness to provide mandatory blood specimens for correlative research.
  • Willingness to provide mandatory tissue specimens for correlative research
  • Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study).


Exclusion Criteria:

  • Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:
    • Pregnant persons;
    • Nursing persons;
    • Persons of childbearing potential who are unwilling to employ adequate contraception.
  • Any of the following prior therapies:
    • Surgery ≤ 4 weeks prior to registration;
    • Chemotherapy ≤ 4 weeks prior to registration;
    • Received single agent anti-PD1/PD-L1 as first line therapy for metastatic disease.
  • 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.
  • 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 situations that would limit compliance with study requirements.
  • Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm.
  • Other active malignancy ≤ 5 years prior to registration.
  • EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix.
  • NOTE: If there is a history of prior malignancy, they must not be receiving other specific treatment for their cancer.
  •  
  • History of myocardial infarction ≤ 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias.
  • 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 ≤ 28 days prior to registration.
  • 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 ≤ 28 days prior to registration;
    • Screening CNS radiographic study ≥ 4 weeks from completion of radiotherapy and ≥ 2 weeks from discontinuation of corticosteroids.
  • History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins.
  • History or current evidence of bleeding disorder, including bleeding diathesis, i.e., any hemorrhage/bleeding event of CTCAE Grade ≥ 2 in ≤ 28 days prior to registration.
  • Taking oral prednisone of ≥ 10 mg daily or equivalent.
  • Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease.

Notes:

  • 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 RNA.
  • 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, Sjögren’s syndrome, Bell’s palsy, Guillain-Barré syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis.

Notes:

  • Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone are eligible.
  • Patients with controlled Type 1 diabetes mellitus on a stable insulin regimen are 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 condition 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).
  • Known active human immunodeficiency virus (HIV) infection (defined as patients who are not on anti-retroviral treatment and have detectable viral load and CD4+ < 500/ml).
    • Note: HIV-positive patients who are well controlled on anti-retroviral therapy are allowed to enroll.
  • History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest computed tomography (CT) scan.
    • Note: History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
  • Severe infections ≤ 4 weeks prior to registration, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia.
  • History of peripheral neuropathy ≥ Grade 2.
  • Known hypersensitivity to docetaxel or polysorbate 80.
Drug, Administration of antineoplastic agent, Chemotherapy, Drug therapy
Cancer, Lung cancer, Non-small cell lung cancer
Bintrafusp alfa, Cancer treatment, Chemotherapy, Docetaxel, Medical Oncology, Non-small cell lung cancer, Respiratory system, docetaxel
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Phase 2 Study of Copanlisib in Combination With Nivolumab in Subjects With Relapsed/Refractory Diffuse Large B-Cell Lymphoma and Primary Mediastinal Large B-Cell Lymphoma

A Study of Copanlisib and Nivolumab in Treating Participants With Recurrent or Refractory Diffuse Large B-cell Lymphoma or Primary Mediastinal Large B-cell Lymphoma

Nabila Bennani
All
18 years and over
Phase 2
This study is NOT accepting healthy volunteers
0000-100804-P01-RST
18-009946
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Inclusion Criteria:

  • Patients must have a histopathologically confirmed diagnosis of diffuse large B-cell lymphoma (DBLCL) or primary mediastinal large B-cell lymphoma.
  • Patients must have measurable disease, defined as at least one lesion that is ≥ 15 mm (≥ 1.5 cm) in the longest axis on cross-sectional imaging and measurable in two perpendicular dimensions per spiral computed tomography (CT) scan or positron-emission tomography (PET)-CT scan.
  • Patients must have disease that is recurrent or refractory to standard therapy; patients must have failed front-line therapy and declined or are not candidates for autologous stem cell transplant (ASCT) or have failed prior ASCT.
  • Age ≥ 18 years.  Because no dosing or adverse event data are currently available on the use of copanlisib and nivolumab combination in patients < 18 years of age, children are excluded from this study, but will be eligible for future pediatric trials. However, if pediatric colleagues and centers are interested in including patients ages 12 to 18 in this trial, this trial then could be available to this group of patients.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
  • Life expectancy of greater than 12 weeks.
  • Patients must have normal organ and marrow function as defined below:
    • White blood cell (WBC) ≥ 3000/mm^3;
    • Absolute neutrophil count (ANC) ≥ 1500/mm^3;
    • Platelet count ≥ 100,000/mm^3;
    • Hemoglobin > 9.0 g/dL;
    • Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (except patients with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL);
    • Aspartate transaminase (AST) ≤ 2.5 x ULN;
    • Serum creatinine ≤ 2.0 mg/dL; OR
    • Calculated creatinine clearance (crcl) ≥ 45 mL/min (if using the Cockcroft-Gault formula):
      • Female CrCl = (140
        •age in years) x weight in kg x 0.85 
                                   72 x serum creatinine in mg/dL
      • Male CrCl = (140
        •age in years) x weight in kg
                                   72 x serum creatinine in mg/dL.
  • Negative urine or serum pregnancy test for females of child bearing potential within 7 days prior to registration:
  • The effects of copanlisib and nivolumab on the developing human fetus are unknown. For this reason, and because the study drugs used in this trial are known to be teratogenic, females of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and for 5 months after the last dose of study drug. Males who are the sexual partners of a female of child-bearing potential must use any contraceptive method with a failure rate of less than 1% per year for the duration of study participation and for a period of 7 months after the last dose of study drug. These periods of required use of contraception have been calculated using the upper limit of the half-life for nivolumab (25 days) and are based on the protocol requirement that females of child-bearing potential use contraception for 5 months and males who are the sexual partners of females of child-bearing potential use contraception for 7 months.
  • Females must not breastfeed for 1 month after last dose.
  • Females of child bearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of nivolumab.
  • A female of child-bearing potential is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal. Menopause is defined clinically as 12 months of amenorrhea in a female over 45 in the absence of other biological or physiological causes. In addition, females under the age of 55 must have a documented serum follicle stimulating hormone (FSH) level less than 40 mIU/mL.
  • Females who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile) and azoospermic males do not require contraception.
  • Should a female of child-bearing potential become pregnant or suspect she is pregnant while she or her partner is participating in this study, she (or the participating partner) should inform the treating physician immediately.
  • Ability to understand and the willingness to sign a written informed consent document.


Exclusion Criteria:

  • Any high grade B-cell lymphoma.
  • Patients who have had chemotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C), anticancer antibodies within 4 weeks, radio or toxin immunoconjugates within 2 weeks, radiation therapy within 3 weeks or major surgery within 2 weeks prior to entering the study:
    • Palliative (limited-field) radiation therapy is permitted if the patient has additional measurable lesions to assess response of therapy.
  • Patients who have not recovered to grade 1 or less from any adverse events due to agents administered more than 4 weeks earlier (excluding alopecia).
  • Patients who are receiving any other investigational agents.
  • Patients should be excluded if they have had prior treatment with a Pi3 kinase inhibitor, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways.
  • Patients who have received autologous stem cell transplant (ASCT) ≤ 8 weeks prior to the first dose of study drug or no adequate count recovery.
  • Patients with a prior history of allogeneic stem cell or solid organ transplantation.
  • Patients with evidence of active disease in the central nervous system (CNS) defined as either the presence of active lesions on MRI obtained within 4 weeks of registration or progressive neurological decline.
  • Patients with primary CNS lymphoma who develop systemic recurrence following standard therapy may be included as long as no active CNS disease is present at the time or enrollment. Similarly, patients with secondary involvement of the CNS from a systemic lymphoma may be included as long as the CNS disease has been optimally treated and they demonstrate no evidence of active CNS disease.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to copanlisib and/or nivolumab.
  • History of severe hypersensitivity reaction to any monoclonal antibody.
  • 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.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, non-healing wound or ulcer, or bone fracture, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Pregnant women are excluded from this study because copanlisib and nivolumab are agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with copanlisib or nivolumab, breastfeeding should be discontinued for 1 month after last dose if the mother is treated with copanlisib or nivolumab.
  • Patients with human immunodeficiency virus (HIV):
  • Patients with human immunodeficiency virus (HIV) are eligible for the study provided they meet the other protocol criteria in addition to the following:
    • Undetectable HIV load by standard PCR clinical assay;
    • Absolute CD4 count of ≥200 mm3;
    • Willing to maintain adherence to combination antiretroviral therapy;
    • No history of AIDS defining condition (other than lymphoma or CD4 cell count < 200 mm3);
    • Likely to have near normal lifespan if not for the presence of relapsed/refractory lymphoma.
  • The Patients with evidence of HBV are eligible provided there is minimal hepatic injury and the patient has undetectable HBV on suppressive HBV therapy. Patient must be willing to maintain adherence to HBV therapy.
  • Patients with previously treated and eradicated hepatitis C virus (HCV) who have minimal hepatic injury are eligible.
  • Patients with active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids, should be excluded; these include but are not limited to patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome should be excluded because of the risk of recurrence or exacerbation of disease; patients with vitiligo, endocrine deficiencies including thyroiditis managed with replacement hormones including physiologic corticosteroids are eligible; patients with rheumatoid arthritis and other arthropathies, Sjögren's syndrome and psoriasis controlled with topical medication and patients with positive serology, such as antinuclear antibodies (ANA), anti-thyroid antibodies should be evaluated for the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible.
  • Patients are permitted to enroll if they have vitiligo, type 1 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 (precipitating event); however, patients with uncontrolled type I or II diabetes mellitus will be excluded; uncontrolled diabetes is defined as hemoglobin A1c (HbA1c) > 8.5%.
  • Patients should be excluded if they have 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; patients are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption); physiologic replacement doses of systemic corticosteroids are permitted, even if < 10 mg/day prednisone equivalents; a brief course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by contact allergen) is permitted.
  • Patients who have had evidence of active or acute diverticulitis, intra-abdominal abscess, and gastrointestinal (GI) obstruction which are known risk factors for bowel perforation should be evaluated for the potential need for additional treatment before coming on study.
  • Patients with other active malignancy ≤ 3 years prior to registration for which active treatment is required must be excluded; patients with composite lymphomas that have a non-B-cell component must be excluded.
    • EXCEPTIONS: Non-melanotic skin cancers or carcinoma-in-situ of the cervix.
  • Copanlisib is primarily metabolized by CYP3A4; therefore, the concomitant use of strong inhibitors of CYP3A4 (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir, indinavir, nelfinavir and saquinavir), and strong inducers of CYP3A4 (e.g., rifampin, phenytoin, carbamazepine, phenobarbital, St. John's Wort) are not permitted from 14 days prior to enrollment until the end of the study.
    • Note: Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. APPENDIX B (Patient Drug Information Handout and Wallet Card) should be provided to patients. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product.
  • Other medications that are prohibited while on copanlisib treatment:
    • Herbal medications/preparations (except for vitamins);
    • Anti-arrhythmic therapy other than beta blockers or digoxin.
Biologic/Vaccine, Drug, Other, Administration of antineoplastic agent, Drug therapy, Immunotherapy for cancer
Cancer, Diffuse large b-cell lymphoma, Lymphoma, Non-Hodgkin's lymphoma, Recurrent cancer
Biological therapy for cancer, Cancer treatment, Copanlisib, Diffuse non-Hodgkin's lymphoma, large cell (clinical), Hematopoietic system, MDX-1106, Medical Oncology, Primary mediastinal (thymic) large B-cell lymphoma, copanlisib, nivolumab
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Actuate 1801: Phase 1/2 Study of 9-ING-41, a Glycogen Synthase Kinase-3 Beta (GSK-3β) Inhibitor, as a Single Agent and Combined With Chemotherapy, in Patients With Refractory Hematologic Malignancies or Solid Tumors

A Study of 9-ING-41 in Patients with Advanced Cancers

Ryan Carr
All
18 years and over
Phase 2
This study is NOT accepting healthy volunteers
0000-100806-P01-RST
18-010674
Show full eligibility criteria
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Inclusion Criteria:


- Patient -

1. Is able to understand and voluntarily sign a written informed consent and is
willing and able to comply with the protocol requirements including scheduled
visits, treatment plan, laboratory tests and other study procedures.

2. Is aged ≥ 18 years

3. Has pathologically confirmed advanced or metastatic malignancy characterized by
one or more of the following:

1. Patient is intolerant of existing therapy(ies) known to provide clinical
benefit for their condition

2. Malignancy is refractory to existing therapy(ies) known to potentially
provide clinical benefit

3. Malignancy has relapsed after standard therapy

4. Malignancy for which there is no standard therapy that improves survival by
at least 3 months

4. Has evaluable tumor(s) by standard radiological and/or laboratory assessments as
applicable to their malignancy
•in Part 3, patients with solid tumors must have
least 1 measurable lesion per response evaluation criteria in solid tumors
(RECIST) v1.1 criteria, measured preferably by computed tomography (CT) scan or
magnetic resonance image (MRI). In the case of patients with glioblastoma
multiforme (GBM) or other central nervous system (CNS) tumors, the tumor must be
measurable, defined as a clearly enhancing tumor with at two perpendicular
diameters at entry equal or superior to 1cm.

5. Has laboratory function within specified parameters (may be repeated):

1. Adequate bone marrow function: absolute neutrophil count (ANC) ≥ 500/mL;
hemoglobin ≥ 8.5 g/dL, platelets ≥ 50,000/mL

2. Adequate liver function: transaminases (aspartate aminotransferase/ alanine
aminotransferase, AST/ALT) and alkaline phosphatase ≤ 3 (≤ 5 X the upper
limit of normal (ULN) in the setting of liver metastasis or infiltration
with malignant cells) x ULN; bilirubin ≤ 1.5 x ULN

3. Adequate renal function: creatinine clearance ≥ 60 mL/min (Cockcroft and
Gault)

4. Adequate blood coagulation: international normalized ratio (INR) ≤ 2.3

5. Serum amylase and lipase ≤ 1.5 x ULN

6. Has adequate performance status (PS): Eastern Co-operative Oncology Group (ECOG)
PS 0-2

7. Has received the final dose of any of the following treatments/ procedures with
the specified minimum intervals before first dose of study drug (unless in the
opinion of the investigator and the study medical coordinator the treatments/
procedures will not compromise patient safety or interfere with study conduct and
with IDMC agreement):

- Chemotherapy, immunotherapy, or systemic radiation therapy
•14 days or ≥ 5
half-lives (whichever is shorter)

- Focal radiation therapy
•7 days

- Systemic and topical corticosteroids
•7 days

- Surgery with general anesthesia
•7 days

- Surgery with local anesthesia
•3 days

8. May continue endocrine therapies (e.g. for breast or prostate cancer) and/or
anti-human epidermal growth factor (Her2) therapies while on this study

9. Women of childbearing potential must have a negative baseline blood or urine
pregnancy test within 72 hours of first study therapy. Women may be neither
breastfeeding nor intending to become pregnant during study participation and
must agree to use effective contraceptive methods (hormonal or barrier method of
birth control, or true abstinence) for the duration of study participation and in
the following 90 days after discontinuation of study treatment

10. Male patients with partners of childbearing potential must take appropriate
precautions to avoid fathering a child from screening until 90 days after
discontinuation of study treatment and use appropriate barrier contraception or
true abstinence

11. Must not be receiving any other investigational medicinal product


Exclusion Criteria:


- Patient -

1. Is pregnant or lactating

2. Is known to be hypersensitive to any of the components of 9-ING-41 or to the
excipients used in its formulation

3. Has not recovered from clinically significant toxicities as a result of prior
anticancer therapy, except alopecia and infertility. Recovery is defined as ≤
Grade 2 CTCAE Version 4.03

4. Has significant cardiovascular impairment: history of congestive heart failure
greater than New York Heart Association (NYHA) Class II, unstable angina, or
stroke within 6 months of the first dose of 9-ING-41, or cardiac arrhythmia
requiring medical treatment detected at screening

5. Has had a myocardial infarction within 12 weeks of the first dose of 9-ING-41 or
has electrocardiogram (ECG) abnormalities that are deemed medically relevant by
the investigator or study medical coordinator

6. Has known symptomatic rapidly progressive brain metastases or leptomeningeal
involvement as assessed by CT scan or MRI. Patients with stable asymptomatic
brain metastases or leptomeningeal disease or slowly progressive disease are
eligible provided that they have not required new treatments for this disease in
a 28-day period before the first dose of study drug, and anticonvulsants and
steroids are at a stable dose for a period of 14 days prior to the first dose of
study drug

7. Has had major surgery (not including placement of central lines) within 7 days
prior to study entry or is planned to have major surgery during the course of the
study (major surgery may be defined as any invasive operative procedure in which
an extensive resection is performed, e.g. a body cavity is entered, organs are
removed, or normal anatomy is altered. In general, if a mesenchymal barrier is
opened (pleural cavity, peritoneum, meninges), the surgery is considered major)

8. Has any medical and/or social condition which, in the opinion of the investigator
or study medical coordinator would preclude study participation

9. Has received an investigational anti-cancer drug in the 14-day period before the
first dose of study drug (or within 5 half-lives if longer) or is currently
participating in another interventional clinical trial

10. Has a current active malignancy other than the target cancer

11. Is considered to be a member of a vulnerable population (for example, prisoners)

Part 3 ARMB
Inclusion Criteria:
Patient -

1. Is able to understand and voluntarily sign a written informed consent and is willing
and able to comply with the protocol requirements including scheduled visits,
treatment plan, laboratory tests and other study procedures

2. Is aged ≥ 18 years

3. Has pathologically confirmed metastatic pancreatic cancer AND is previously untreated
with systemic agents in the recurrence/metastatic setting.

4. Must have at least 1 measurable lesion per RECIST v1.1, measured preferably by
computed tomography (CT) scan or magnetic resonance image (MRI)

5. Has laboratory function within specified parameters (may be repeated):

e. Adequate bone marrow function: absolute neutrophil count (ANC) ≥ 500/mL; hemoglobin
≥ 8.5 g/dL, platelets ≥ 75,000/mL f. Adequate liver function: transaminases (aspartate
aminotransferase/ alanine aminotransferase, AST/ALT) and alkaline phosphatase ≤ 3 (≤
10 X the upper limit of normal (ULN) in the setting of liver metastasis or
infiltration with malignant cells) x ULN; bilirubin ≤ 1.5 x ULN Adequate renal
function: creatinine clearance ≥ 30 mL/min (Cockcroft and Gault)

6. Has Eastern Co-operative Oncology Group (ECOG) PS 0 or 1

7. Has received the final dose of any of the following treatments/ procedures with the
specified minimum intervals before first dose of study drug:

- Focal radiation therapy
•7 days

- Surgery with general anesthesia
•7 days

- Surgery with local anesthesia
•3 days

8. May have received treatment with fluorouracil or gemcitabine as a radiation sensitizer
in the adjuvant setting if the treatment was received at least 6 months before study
enrollment

9. May have received neoadjuvant chemotherapy with FOLFIRINOX if last dose given at least
6 months before study enrollment

10. May have received prior cytotoxic doses of systemic chemotherapy in the adjuvant
setting if last dose given at least 6 months before study enrollment

11. Women of childbearing potential must have a negative baseline blood or urine pregnancy
test within 72 hours of first study therapy. Women may be neither breastfeeding nor
intending to become pregnant during study participation and must agree to use
effective contraceptive methods (hormonal or barrier method of birth control, or true
abstinence) for the duration of study participation and in the following 90 days after
discontinuation of study treatment

12. Male patients with partners of childbearing potential must take appropriate
precautions to avoid fathering a child from screening until 90 days after
discontinuation of study treatment and use appropriate barrier contraception or true
abstinence

13. Must not be receiving any other investigational medicinal product

Patient who meets ANY of the following criteria is not eligible for this Part 3 study Arm
B:


Exclusion Criteria:


1. Is pregnant or lactating

2. Is known to be hypersensitive to any of the components of 9-ING-41 or to the
excipients used in its formulation

3. Has endocrine or acinar pancreatic carcinoma

4. Has not recovered from clinically significant toxicities as a result of prior
anticancer therapy, except alopecia and/or infertility. Recovery is defined as ≤ Grade
2 severity per CTCAE, v5.0

5. Has significant cardiovascular impairment: history of congestive heart failure greater
than New York Heart Association (NYHA) Class II, unstable angina, or stroke within 6
months of the first dose of study therapy, or uncontrolled cardiac arrhythmia

6. Has had a myocardial infarction within 12 weeks of the first dose of study therapy or
has electrocardiogram (ECG) abnormalities that are deemed medically relevant by the
investigator

7. Has symptomatic rapidly progressive brain metastases or leptomeningeal involvement as
assessed by CT scan or MRI. Patients with stable brain metastases or leptomeningeal
disease or slowly progressive disease are eligible provided that they have not
required new treatments for this disease in a 28-day period before the first dose of
study drug, and anticonvulsants and steroids are at a stable dose for a period of 14
days prior to the first dose of study drug

8. Has had major surgery (not including placement of central lines) within 7 days prior
to study entry or is planned to have major surgery during the course of the study
(major surgery may be defined as any invasive operative procedure in which an
extensive resection is performed, e.g., a body cavity is entered, organs are removed,
or normal anatomy is altered. In general, if a mesenchymal barrier is opened (pleural
cavity, peritoneum, meninges), the surgery is considered major)

9. Has any medical and/or social condition which, in the opinion of the investigator or
study medical coordinator would preclude study participation.

10. Has received an investigational anti-cancer drug in the 14-day period before the first
dose of study drug (or within 5 half-lives if longer) or is currently participating in
another interventional clinical trial.

11. Has a current active malignancy other than pancreatic cancer

12. Is considered to be a member of a vulnerable population (for example, prisoners).

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Eligibility last updated 2/9/23. Questions regarding updates should be directed to the study team contact.

Drug, Administration of antineoplastic agent, Drug therapy
Malignant neoplastic disease
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MS200647_0005: A Multicenter, Double Blind, Randomized, Controlled Study of M7824 With Concurrent Chemoradiation Followed by M7824 Versus Concurrent Chemoradiation Plus Placebo Followed by Durvalumab in Participants With Unresectable Stage III Non-small Cell Lung Cancer

A Study to Evaluate M7824 with Concurrent Chemoradiation (cCRT) in Unresectable Stage III Non-small Cell Lung Cancer (NSCLC)

Aaron Mansfield
All
18 years and over
Phase 2
This study is NOT accepting healthy volunteers
0000-100808-P01-RST
19-002241
Show full eligibility criteria
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Inclusion Criteria:

  • Are ≥ 18 years of age at the time of signing the informed consent.
    • In Japan, if a patient is < 20 years, the written informed consent from his/her parent or guardian will be required in addition to the patient’s written consent.
  • Participants must have measurable or non-measurable but evaluable disease assessed by the Investigator. Participants must have histologically documented NSCLC who present with Stage III locally advanced, unresectable disease (International Association for the Study of Lung Cancer Staging Manual in Thoracic Oncology [IASLC Staging Manual in Thoracic Oncology], v8).
  • 3. Availability of tumor material (< 6 months old) adequate for biomarker analysis is mandatory for all participants and central laboratory confirmation is required. For participants enrolled in the safety run-in, PD-L1 expression will be tested retrospectively by a central laboratory. For participants enrolled in the expansion part of the study, PD-L1 expression must be tested by the central laboratory and results available before randomization. Only results from the central laboratory testing will be used for randomization and if PD-L1 status is non-evaluable, the participant is not eligible for this study. Tumor samples obtained by endoscopic biopsies, core needle biopsies, excisional biopsies, punch biopsies, and surgical specimens that are < 6 months old and adequate for biomarker analysis are acceptable. Biopsies obtained by fine needle aspiration are not acceptable.
  • Participants with tumor harboring an EGFR sensitizing (activating) mutation, ALK translocation, ROS-1 rearrangement are eligible. These tests are not required for enrollment in the study.
  • Participants with ongoing post-obstructive pneumonia due to the tumor are eligible.
  • If a pleural effusion is present, the following criteria must be met to exclude malignant involvement (incurable T4 disease):
    • When pleural fluid is visible on both the CT scan and on a chest x-ray, a thoracentesis is required to confirm that the pleural fluid is cytologically negative;
    • Participants with exudative pleural effusions are excluded, regardless of cytology;
    • Participants with effusions that are minimal; i.e., are too small to safely tap are eligible.
  • Participants must be at least 3 weeks from prior thoracotomy (if performed).
  • Participants must have adequate pulmonary function defined as a forced expiratory volume in 1 second (FEV1) ≥ 1.2 liters or ≥ 50% of predicted normal volume measured within 3 weeks prior to randomization. If participants do not meet the above criteria, treatment with inhaled steroids and bronchodilators can be initiated if clinically indicated and eligibility can be reassessed after 1-2 weeks.
  • ECOG performance status of 0 to 1 at Screening and on the day of first dose.
  • Life expectancy ≥ 12 weeks.
  • Have adequate organ function as indicated by the following laboratory values:
    • Adequate hematological function defined by absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L, platelet count ≥ 100 × 109/L, and hemoglobin ≥ 9 g/dL;
    • Adequate hepatic function defined by a total bilirubin level ≤ 1.5 × upper limit of normal (ULN), an aspartate aminotransferase (AST) level ≤ 3.0 × ULN, an alanine aminotransferase (ALT) level ≤3.0 × ULN and alkaline phosphatase ≤ 2.5 ULN;
    • Adequate renal function defined by creatine ≤ 1.5 × ULN or calculated creatinine clearance (CrCl) ≥ 50 mL/min for participant with Cr > 1.5 × ULN (GFR can also be used).
      • Note: CrCl  should be calculated per institutional standard. If no local guideline is available, CrCl should be calculated using the Cockcroft-Gault Method:
      • CrCl = ((140-age) * weight (kg) * (0.85 for females only)) / (72 * creatinine).
    • Adequate coagulation function defined as international normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 × ULN unless the participant is receiving anticoagulant therapy and activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless the participant is receiving anticoagulant therapy.
  • Contraceptive use by males or females will be consistent with local regulations on contraception methods for those participating in clinical studies.
    • Male Participants:
      • Contraceptive measures should be continued as per guidance specified in labeling document for approved chemotherapies. If not specified, continue measures similar to investigational agent i.e agree to the following during the study intervention period and for at least 6 months after the last dose of study intervention
      • Refrain from donating sperm; PLUS, either:
        • Abstain from intercourse with a WOCBP;
          • OR
        • Use a male condom: When having sexual intercourse with a WOCBP, who is not currently pregnant, and advise her to use a highly effective contraceptive method with a failure rate of < 1% per year, since a condom may break or leak.
    • Female Participants:
      • Are not pregnant or breastfeeding, and at least one of the following conditions applies:
        • Not a WOCBP.
          • OR
        • If a WOCBP, use a highly effective contraceptive method (i.e., with a failure rate of < 1% per year), preferably with low user dependency, for the following time periods:
          • Before the first dose of the study intervention(s), if using hormonal contraception:
          • Has completed at least one 4-week cycle of an oral contraception pill and either had or has begun her menses; OR
          • Has used a depot contraceptive or extended-cycle oral contraceptive for least 28 days and has a documented negative pregnancy test using a highly sensitive assay.
          • During the intervention period.
        • Contraceptive measures should be continued as per guidance specified in labeling document for approved chemotherapies. If not specified, continue measures similar to investigational agent i.e., after the study intervention period (i.e., after the last dose of study intervention is administered) for at least 4 months after the last dose of study intervention and agree not to donate eggs (ova, oocytes) for reproduction during this period.
      • Have a negative pregnancy test, as required by local regulations, on W1D1 before the first dose of study intervention.
      • Additional requirements for pregnancy testing during and after study intervention are in SoA.
      • The Investigator reviews the medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a female with an early undetected pregnancy.
  • Can give signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and this protocol.


Exclusion Criteria:
 

  • Participants with mixed small cell with non-small cell lung cancer histology.
  • Greater than minimal, exudative, or cytologically positive pleural effusions.
  • Recent major surgery within 4 weeks prior to entry into the study (excluding the placement of vascular access) that would prevent administration of study drug.
  • Active or prior documented inflammatory bowel disease (e.g., Crohn’s disease, ulcerative colitis).
  • History of organ transplant that requires therapeutic immunosuppression.
  • Significant acute or chronic infections including, among others:
    • Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (testing at Screening is not required). If an Investigator has a strong suspicion of HIV infection without known history for a participant in Screening, however participant refuses testing, discuss with Medical Monitor to assess eligibility. (Note: HIV testing is not mandated for study inclusion; however, if it is performed at any point in Screening or while on study, a site must consent the participant for HIV testing as per local standard guidance);
    • Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection (HBV surface antigen positive and HBV core antibody positive with reflex to positive HBV DNA, or HBV core antibody positive alone with reflex to positive HBV DNA, or positive HCV antibody with reflex to positive HCV RNA) at Baseline. Discuss with the Medical Monitor if history of HBV or HCV  infection is known. If medically indicated, participants infected with HBV must be treated and on a stable dose of antivirals (e.g, entecavir, tenofovir, or lamivudine; adefovir or interferon are not allowed) at study entry and with planned monitoring and management according to appropriate labeling guidance. Participants on active HCV therapy at study entry must be on a stable dose without documented clinically significant impaired liver function test or hematologic abnormalities (must meet criteria above) and with planned monitoring and management according to appropriate labeling guidance. HBV and/or HCV viral titers must be monitored according to SoA in these participants.
    • Participants with active tuberculosis (history of exposure or history of positive tuberculosis test; plus presence of clinical symptoms, physical, or radiographic findings).
  • Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses, active uveitis or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the patient to give written informed consent. Participants with history of bleeding diathesis or recent major bleeding events considered by the Investigator as high risk for investigational drug treatment are also excluded.
  • Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days before randomization.
  • Known clinical history of tuberculosis, lung sarcoidosis and Interstitial Lung Diseases.
  • History of another primary malignancy within 3 years prior to starting study drug, except for adequately treated basal or squamous cell carcinoma of the skin, adequately treated carcinoma in situ, e.g., cancer of the cervix in situ, superficial bladder cancer. History of other localized malignancies treated with curative intent needs to be discussed with the Medical Monitor.
  • Uncontrolled neuropathy Grade 2 or greater regardless of cause.
  • Significant hearing loss and participants unwilling to accept potential for further hearing loss (Investigator should consider treating the participant with carboplatin/paclitaxel).
  • Any prior systemic cytotoxic chemotherapy for their NSCLC or any antibody or drug targeting T-cell coregulatory proteins (immune checkpoints) such as anti-PD-(L)1, or anti-CTLA-4 antibody.
  • Current or prior use of immunosuppressive medication within 28 days before the first dose of study drug, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid. Systemic steroid administration required to manage toxicities arising from radiation therapy delivered as part of the cCRT for locally advanced NSCLC is allowed.
  • Active autoimmune disease that has required systemic treatment in past 1 year (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs), OR is receiving systemic steroid therapy < 3 days prior to the first dose of study intervention or receiving any other form of immunosuppressive medication. Participants requiring hormone replacement with corticosteroids are eligible if the steroids are administered only for the purpose of hormonal replacement and at low doses (typically ≤ 10 mg of prednisone or equivalent per day). Equivalent hydrocortisone doses are also permitted if administered as a replacement therapy. Corticosteroid use on study as a premedication for IV contrast allergies/reactions (related to scans) is allowed and must be documented. This must be discussed with Medical Monitors for clinical indications in which participants may require a higher dose. Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent. Participants with diabetes Type I, vitiligo, alopecia, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible.  Consult Medical Monitor for other autoimmune diseases.
  • Receipt of live attenuated vaccination within 30 days of receiving study drug.
  • Use of a prohibited concomitant drug within 4 weeks randomization.
  • Known severe hypersensitivity (Grade ≥ 3 National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] v5.0) to study interventions or any components in their formulations, or uncontrolled asthma (i.e., 3 or more features of partially controlled asthma).
  • Participation in another clinical study with an investigational product within the last 4 weeks.
  • Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or the follow-up period of an interventional study.
  • ≥ 10% weight loss within the past month.
  • Female patients who are pregnant, breast-feeding or male or female patients of reproductive potential who are not employing an effective method of birth control.
  • Any condition that, in the opinion of the Investigator, would interfere with evaluation of the study drug or interpretation of participant safety or study results.

 

Administration of antineoplastic agent, Combined chemotherapy and radiation therapy, Drug therapy, Immunotherapy for cancer, Biologic/Vaccine, Drug, Radiation
Cancer, Lung cancer, Non-small cell lung cancer
Bintrafusp alfa, Biological therapy for cancer, Cancer treatment, Chemotherapy, Durvalumab [USAN:INN], Medical Oncology, Non-small cell carcinoma of lung, TNM stage 3, Radiation therapy, Respiratory system, Tumor surgically unresectable, durvalumab
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SMX18001: An Open-Label, Randomized, Multicenter Study Evaluating the Activity of Lasofoxifene Relative to Fulvestrant for the Treatment of Postmenopausal Women With Locally Advanced or Metastatic ER/HER2− Breast Cancer With an ESR1 Mutation

A Study to Evaluate Lasofoxifene versus Fulvestrant in Advanced or Metastatic ER+/HER2− Breast Cancer Patients with an ESR1 Mutation

Matthew Goetz
Female
18 years and over
Phase 2
This study is NOT accepting healthy volunteers
0000-100824-P01-RST
19-001642
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Inclusion Criteria:
 

  • Pre- or postmenopausal.  Postmenopausal women are defined as:
    • 60 years of age with no vaginal bleeding over the prior year; or
    • < 60 years with "premature menopause" or "premature ovarian failure” manifest itself with secondary amenorrhea for at least 1 year and follicle stimulating hormone (FSH) and estradiol levels in the postmenopausal range according to institutional standards; or
    • surgical menopause with bilateral oophorectomy.
      • Note: Premenopausal women who meet all of the other entry criteria must be maintained on ovarian suppression (such as Lupron) during the study and subjects counseled to use appropriate contraception to prevent pregnancy.
  • If possible, a biopsy of metastatic breast cancer tissue will be obtained to provide histological or cytological confirmation of ER+ and HER2− disease as assessed by a local laboratory, according to the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines, using slides, paraffin blocks, or paraffin samples. If a biopsy is not possible, the ER and HER2 status from the tissue obtained at the time of the original diagnosis must confirm that the subject’s cancer is ER+ and HER2−.
  • Locally advanced or metastatic breast cancer with radiological or clinical evidence of progression while on an AI in combination with a CDK4/6 inhibitor for advanced breast cancer with demonstrated prior sensitivity to endocrine therapy (recurrence or progression after at least 12 months of treatment in the metastatic setting).
  • Locally advanced or metastatic breast cancer with measurable (according to RECIST 1.1 and/or non-measurable lesions.
  • At least one or more of the following ESR1 point mutations as assessed in cell-free circulating tumor DNA (ctDNA) obtained from a blood (plasma) or tissue sample: Y537S, Y537C, D538G, E380Q, S463P, V534E, P535H, L536H, L536P, L536R, L536Q, or Y537N.  The ctDNA sample collection must be obtained within 90 days prior to randomization to determine eligibility and baseline.
    • Note: a prior genomic test confirming that the subject has an ESR1 mutation can be used to determine eligibility; however, an ESR1 sample must also be collected within 30 days of randomization.
  • Subjects who have not received cytotoxic chemotherapy or who have received one cytotoxic chemotherapy regimen in the neo-adjuvant or adjuvant setting prior to entry into the trial; and/or no more than one chemotherapy regimen for metastatic breast cancer. Subjects must be free of all chemotherapy acute toxicity excluding alopecia and Grade II peripheral neuropathy before study entry.
  • ECOG performance score of 0 or 1.
  • Adequate organ function as shown by:
    • absolute neutrophil count (ANC) ≥ 1,500 cells/mm^3;
    • platelet count ≥ 100,000 cells/mm^3;
    • hemoglobin ≥ 9.0 g/dl;
    • ALT and AST levels ≤ 2.5 upper limit of normal (ULN) or < 5 in the presence of visceral metastasis;
    • total serum bilirubin ≤ 0.5 x ULN (≤ 3.0 x ULN for subjects known to have Gilbert Syndrome);
    • alkaline phosphatase level < 2.5 x ULN;
    • creatinine clearance of 40 ml/min or greater as calculated by the Cockcroft-Gault formula;
    • international normalized ratio (INR) and activated partial thromboplastin (aPTT) < 2.0 x ULN.
  • Able to swallow tablets.
  • Able to understand and voluntarily sign a written informed consent before any screening procedures.


Exclusion Criteria:
 

  • Prior use of everolimus or other mammalian target of rapamycin (mTOR) inhibitor or phosphoinositide 3-kinase inhibitor (PI3K) inhibitors are excluded unless discontinued due to reasons other than disease progression.
  • Presence of brain metastasis.
  • Lymphangitic carcinomatosis involving the lung.
  • Impending visceral crisis in need of cytotoxic chemotherapy as assessed by the investigator. Radiotherapy within 30 days prior to randomization except in case of localized radiotherapy for analgesic purposes or for lytic lesions at risk of fracture, which can then be completed within 7 days prior to randomization. Subjects must have recovered from radiotherapy toxicities prior to randomization.
  • History of long QTC syndrome or a QTC of > 480 msec.
  • History of a pulmonary embolus (PE) or deep vein thrombosis (DVT) within the last 6 months or any known thrombophilia. Subjects stable on anti-coagulants for maintenance are eligible as long as the DVT and/or PE occurred > 6 months prior to enrollment and there is no evidence for active thrombosis. The use of low dose acetylsalicylic acid (ASA) is permitted.
  • Any significant co-morbidity that would impact the study or the subject’s safety.
  • History of a positive human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) at Screening. Subjects cured of hepatitis C (no viral load) are eligible.
  • History of malignancy within the past 5 years (excluding breast cancer), except basal cell or squamous cell carcinoma of the skin curatively treated by surgery, or early stage cervical cancer.
  • History of vaginal bleeding over the last year unless it is documented that the bleeding was due to non-uterine causes (e.g., vaginal atrophy).
  • Uncontrolled hypertension defined as sitting systolic pressure >160 mm Hg or diastolic pressure > 100 mm Hg at Screening.
  • History of non-compliance to medical regimens.
  • Unwilling or unable to comply with the protocol.
  • Current participation in any clinical research trial involving an investigational drug or device within the last 30 days.

 

Drug, Administration of antineoplastic agent, Drug therapy
Breast cancer, Cancer
fulvestrant, Cancer treatment, Estrogen receptor positive tumor, Fulvestrant, Human epidermal growth factor 2 negative carcinoma of breast, Lasofoxifene, Medical Oncology, Secondary malignant neoplasm of female breast, Hormone therapy for breast cancer
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A Phase 1b Study of Berzosertib in Combination With Radiation Therapy to Overcome Therapeutic Resistance in Chemotherapy Resistant Triple Negative and Estrogen and/or Progesterone Receptor Positive, HER2 Negative Breast Cancer

A Study to Test the Addition of berzosertib to Usual Radiation Treatment for Chemotherapy-Resistant Breast Cancer

Robert Mutter
All
18 years and over
Phase 1
This study is NOT accepting healthy volunteers
0000-100827-P01-RST
19-012508
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Inclusion Criteria:

  • Males or females age ≥ 18 years
  • Patient has non-metastatic, histologically confirmed primary or locoregionally recurrent estrogen receptor (ER) ≤ 10%, progesterone receptor (PR) ≤ 10%, and HER2-negative breast cancer (triple negative breast cancer [TNBC]) either using the baseline biopsy specimen or the post-neoadjuvant chemotherapy (NAC) residual surgical specimen and residual cancer burden (RCB)2 or RCB3, as defined by Symmans et al., 2007, and received neoadjuvant anthracycline and/or taxane-based chemotherapy OR patient has non-metastatic, histologically confirmed primary ER > 10% and/or PR > 10%, HER2-negative breast cancer with RCB3 and received neoadjuvant anthracycline and/or taxane-based chemotherapy OR patient has locoregionally recurrent TNBC or ER > 10% and/or PR > 10%, HER2-negative breast cancer.
    • Note: The RCB can be calculated at http://www3.mdanderson.org/ap/medcalc/index.cfm?pagename=jsconvert2
    • Note: Results from any CLIA-certified lab are acceptable for the purpose of determining study eligibility.
    • Note: For patients with primary breast cancer, there is no minimum number of neoadjuvant cycles required provided the patient received an anthracycline or taxane preoperatively. Patients with locoregionally recurrent breast cancer are not required to have received preoperative chemotherapy.
  • Patient has undergone total mastectomy or wide local excision with axillary staging, and the margins of the resected wide local excision or mastectomy specimens are free of invasive tumor and ductal carcinoma in situ (DCIS) or patient has undergone axillary surgery for regionally recurrent breast cancer. Unresected axillary level III, internal mammary, and supraclavicular nodal disease is permitted.
    • Note: For patients who have undergone mastectomy, immediate reconstruction is allowed.
  • Patients must have completed their final breast surgery including re-excision of margins for invasive cancer and DCIS, or received their last adjuvant chemotherapy infusion,  within 90 but not fewer than 21 days prior to registration unless patient received postoperative chemotherapy in which case patients must have completed their adjuvant chemotherapy within 90 days but not fewer than 28 days prior to registration. but no sooner than 21 days prior to the initiation of RT for surgery or 28 days for chemotherapy. Post-radiotherapy adjuvant systemic therapy (e.g. adjuvant capecitabine) may not be completed less than 21 days prior to the first fraction of RT or begin less than 28 days from the last fraction of RT.
  • Patient must have recovered from surgery with the incision completely healed and no signs of infection prior to registration.
  • Patients must be proceeding with breast/chest wall and regional nodal irradiation including internal mammary node treatment. BFor patients with bilateral breast cancer is permitted provided that , RT ismust be indicated and administered only to one side.
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
  • Willing to provide tissue and blood samples for correlative research:
    • Leukocytes ≥ 3,000/mcL;
    • Absolute neutrophil count ≥ 1,500/mcL;
    • Platelets ≥ 100,000/mcL;
    • Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN);
    • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) ≤ 3 x institutional ULN;
    • Creatinine ≤ institutional ULN; OR
    • Glomerular filtration rate (GFR) ≥ 60 mL/min/1.73 m^2 for patients with creatinine levels above ULN.
  • 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.
  • Negative urine or serum pregnancy test for individuals of childbearing potential.
    • Note: The effects of berzosertib on the developing human fetus are unknown. For this reason and because DNA-damage repair inhibitors as well as radiation used in this trial are known to be teratogenic, 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 and for the duration of study participation, and for 6 months after completion of M6620 administration. 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.  Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 6 months after completion of berzosertib administration.
  • Ability to understand and the willingness to sign a written informed consent document.


Exclusion Criteria:

  • Patients who have had chemotherapy within 4 weeks prior to entering the study.
  • Prior RT to the ipsilateral chest wall or ipsilateral breast or thorax. Individuals with prior RT to the contralateral breast or chest wall are eligible.
  • Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > grade 1) with the exception of alopecia and grade 1-2 taxane-induced neuropathy which will be permitted.
  • Patients who are receiving any other investigational agents or concomitant anti-neoplastic treatment, except endocrine therapies and bisphosphonates which are permitted without restriction even during protocol treatment. Postoperative chemotherapy is allowed but must be discontinued >28 days prior to registration.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to berzosertib.
  • Berzosertib is primarily metabolized by CYP3A4; therefore, concomitant administration with strong inhibitors of CYP3A4 (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir, indinavir, nelfinavir, and saquinavir) or inducers of CYP3A4 (e.g., rifampin, phenytoin, carbamazepine, phenobarbital, St. John's wort) should be avoided. Patients requiring any medications or substances that are strong inhibitors or inducers of CYP3A during the course of the study and for 14 days prior to enrollment are ineligible. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product.
  • Patients with uncontrolled intercurrent illness. This includes but is not limited to, ongoing uncontrolled serious infection requiring IV antibiotics at the time of registration, symptomatic congestive heart failure, unstable angina pectoris, symptomatic/uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Active systemic lupus, scleroderma, or dermatomyositis with a CPK level above normal.
  • Pregnant women are excluded from this study because berzosertib as a DNA damage repair inhibitor may have the potential for teratogenic or abortifacient. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with berzosertib, breastfeeding should be discontinued if the mother is treated with berzosertib.
  • Patients with known hereditary syndromes predisposing to radiosensitivity such as Li Fraumeni syndrome and ataxia telangiectasia are excluded from the study. Patients with mutations in breast cancer predisposition genes such as BRCA1, BRCA2, PALB2, CHEK2, and ATM are eligible.
  • Patients with a prior or concurrent malignancy, excluding non-melanoma skin cancers and non-invasive cancers whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen.
Drug, Other, Radiation, Administration of antineoplastic agent, Drug therapy, Excision of lesion of breast, Radiotherapy to breast
Breast cancer, Cancer, Triple-negative breast cancer
Berzosertib [USAN], Cancer treatment, Estrogen receptor positive tumor, Hormone receptor positive malignant neoplasm of breast, Human epidermal growth factor 2 negative carcinoma of breast, Medical Oncology, Progesterone receptor positive tumor, Radiation therapy, Radiation therapy for breast cancer, Triple-negative breast cancer
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TRANSCEND CLL 004 - An Open-Label, Phase 1/2 Study of JCAR017 in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma (017004)

A Study Evaluating the Safety and Effectiveness of JCAR017 to Treat Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL)

Saad Kenderian
All
18 years and over
Phase 1/2
This study is NOT accepting healthy volunteers
0000-100830-P01-RST
19-001564
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Inclusion Criteria:
 

  • Age ≥ 18 years at the time of consent.
  • Signed written informed consent.
  • JCAR017 monotherapy and ibrutinib + JCAR017 combination cohorts must have diagnosis of:
    • CLL with an indication for treatment based on the Investigator’s opinion and measurable disease (any of the following: bone marrow involvement by ≥ 30% lymphocytes, peripheral blood lymphocytosis > 5 × 10^9 /L, and/or measurable lymph nodes ≥ 1.5 cm in the greatest transverse diameter and/or hepatomegaly or splenomegaly); or
    • SLL (lymphadenopathy and/or splenomegaly and < 5 × 10^9 CD19+ CD5+ clonal B lymphocytes/L [< 5000/µL] in the peripheral blood at diagnosis with measurable disease defined as at least one lesion ≥ 1.5 cm in the greatest transverse diameter) that is biopsy-proven SLL Venetoclax + JCAR017 combination cohorts must have diagnosis of:
    • CLL or SLL with an indication for treatment based on the Investigator’s opinion and measurable disease (any of the following: measurable lymph nodes ≥ 1.5 cm in the greatest transverse diameter and/or hepatomegaly or splenomegaly), and demonstration of CLL cells in the peripheral blood by flow cytometry.
  • Subjects (other than those in the ibrutinib + JCAR017 combination therapy cohort) must have received and failed BTKi treatment or have been deemed ineligible for BTKi therapy due to requirement for full dose anticoagulation or history of arrhythmia. Failure to BTKi is defined as having stable disease or progressive disease (PD) as best response, or progression after previous response, or discontinuation due to intolerance. Intolerance is defined as failure to tolerate treatment due to unmanageable toxicity.
  • Subjects in the JCAR017 monotherapy cohorts must have received previous treatment as follows:
    • Subjects with CLL or SLL and high-risk features, defined as having complex cytogenetic abnormalities (3 or more chromosomal abnormalities), 17p deletion, TP53 mutation, or unmutated immunoglobulin heavy chain variable region (IGHV), must have failed at least 2 lines of prior therapy;
    • Subjects with CLL or SLL and standard-risk features must have failed at least 3 lines of prior therapy.
  • Subjects in the ibrutinib + JCAR017 combination cohorts must either:
    • be receiving ibrutinib, or other BTKi, and progressing at the time of study enrollment; or
    • be receiving ibrutinib, or other BTKi, for at least 6 months with a response less than CR and have high-risk features, as defined in inclusion criterion 5a; or
    • have BTK or phospholipase C gamma 2 (PLCγ2) mutations per local laboratory assessment, with or without progression on ibrutinib; or
    • have previously received ibrutinib, or other BTKi, and have no contraindications to initiate or reinitiate ibrutinib (i.e., ibrutinib was not discontinued due to intolerability and subject has no medical contraindications such as arrhythmia or need for anticoagulation) Subjects in the ibrutinib + JCAR017 combination therapy cohorts enrolled under at least amendment 5, must also meet the below criteria:
    • have progressed on a BTKi and f. have received prior therapy with venetoclax which is considered if they meet one of the following criteria:
      • the subject continued on venetoclax due to disease progression or intolerability and if the subject’s disease met indications for further therapy per iwCLL 2018 criteria; or
      • the subject failed to achieve an objective response within 3 months of initiating therapy. Subjects in the venetoclax + JCAR017 combination cohorts must:
    • Have failed at least 1 prior line of therapy, including having failed BTKi therapy or have been deemed ineligible to receive BTKi, as defined in Inclusion Criterion #4;
    • Be venetoclax naïve (required for dose expansion cohort); or
      • If prior venetoclax, (only for dose escalation cohort) (1) have no contraindications to reinitiation of venetoclax based on prior intolerance and (2) have had at least 6 months elapsed since the last dose of venetoclax, if either of the following criteria are met:
      • the best response was stable disease; or
      • the subject experienced disease progression on venetoclax within 6 months of venetoclax discontinuation.
  • Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1.
  • Assessed by the Investigator to have adequate bone marrow function to receive lymphodepleting chemotherapy.
  • Adequate organ function, defined as:
    • Serum creatinine ≤ 1.5 × age-adjusted upper limit of normal (ULN) OR calculated creatinine clearance (Cockcroft and Gault) > 30 mL/min;
    • Alanine aminotransferase (ALT) ≤ 5 × ULN and total bilirubin < 2.0 mg/dL (or < 3.0 mg/dL for subjects with Gilbert’s syndrome or leukemic infiltration of the liver);
    • Adequate pulmonary function, defined as ≤ Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 dyspnea and saturated oxygen (SaO2) ≥ 92% on room air;
    • Adequate cardiac function, defined as left ventricular ejection fraction (LVEF) ≥ 40% as assessed by echocardiogram (ECHO) or multiple uptake gated acquisition (MUGA) scan performed within 30 days prior to determination of eligibility Subjects in the venetoclax + JCAR017 combination dose escalation and expansion cohorts must have:
      • Hemoglobin ≥ 9 g/dL, absolute neutrophil count (ANC) ≥ 500/mm^3 , and platelets ≥ 75,000/mm^3 , unless cytopenias judged by the Investigator to be due to CLL infiltration of the bone marrow.
  • Subject either currently has central vascular access or is a candidate to receive central vascular access or peripheral vascular access for leukapheresis procedure.
  • If prior CD19-targeted therapy has been administered, subject must have CD19-positive disease confirmed by immunohistochemistry or flow cytometry since completing the prior CD19-targeted therapy.
  • Females of childbearing potential must either commit to true abstinence from heterosexual contact or agree to use one highly effective method of contraception from screening until at least 1 year after receiving lymphodepleting chemotherapy.
  • Females of childbearing potential must have a negative serum beta human chorionic gonadotropin (ß-hCG) pregnancy test result at screening and within 48 hours prior to the first dose of lymphodepleting therapy.
  • Males who have partners of childbearing potential must practice true abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential for at least 1 year after receiving lymphodepleting chemotherapy even if he has undergone a successful vasectomy.


Exclusion Criteria:

  • Subjects with known active central nervous system (CNS) involvement by malignancy. Subjects with prior CNS disease that has been effectively treated will be eligible if treatment was completed at least 3 months prior to enrollment with no evidence of symptomatic disease and stable abnormalities on repeat imaging.
  • History of another primary malignancy that has not been in remission for at least 2 years. (The following are exempt from the 2-year limit: nonmelanoma skin cancer, completely resected stage 1 solid tumor with low risk for recurrence, curatively treated localized prostate cancer, cervical carcinoma in situ on biopsy or a squamous intraepithelial lesion on Pap smear, and in situ breast cancer that has been completely resected.).
  • Subjects with Richter’s transformation.
  • Prior treatment with any gene therapy product.
  • Active hepatitis B, or active hepatitis C (Subjects with a negative polymerase chain reaction (PCR) assay for viral load for hepatitis B or C are permitted; subjects positive for hepatitis B surface antigen and/or anti-hepatitis B core antibody with negative viral load are eligible and should be considered for prophylactic antiviral therapy), or history of or active human immunodeficiency virus (HIV) infection.
  • Systemic fungal, bacterial, viral, or other infection that is not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment).
  • Presence of acute or extensive chronic graft versus host disease (GVHD).
  • History of any one of the following cardiovascular conditions within the past 6 months: Class III or IV heart failure as defined by the New York Heart Association (NYHA), cardiac angioplasty or stenting, myocardial infarction, unstable angina, or other clinically significant cardiac disease.
  • History or presence of clinically relevant CNS pathology such as epilepsy, generalized seizure disorder, aphasia, stroke with current neurologic sequelae, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, cerebral edema, or psychosis.
  • Pregnant or nursing (lactating) women.
  • Use of any of the following medications or treatments within the noted time prior to leukapheresis:
    • Alemtuzumab within 6 months prior to leukapheresis;
    • Allogeneic hematopoietic stem cell transplant within 100 days prior to leukapheresis;
    • Cladribine within 3 months prior to leukapheresis;
    • Donor lymphocyte infusions (DLI) within 2 months prior to leukapheresis;
    • Radiation including large bone marrow fields such as sternum or pelvis within 6 weeks prior to leukapheresis;
    • Fludarabine within 4 weeks prior to leukapheresis;
    • GVHD therapies such as calcineurin inhibitors, methotrexate or other chemotherapeutics, mycophenolate mofetil, rapamycin, or immunosuppressive antibodies (such as anti-tumor necrosis factor-α [TNFα], anti-interleukin-6 [IL-6], or anti-interleukin-6 receptor [IL-6R]) within 4 weeks prior to leukapheresis;
    • Cyclophosphamide, ifosfamide, bendamustine, chlorambucil, or melphalan within 2 weeks prior to leukapheresis;
    • Therapeutic doses of corticosteroids (defined as > 20 mg/day prednisone or equivalent) within 7 days prior to leukapheresis;
    • Anti-CD20 monoclonal antibodies within 7 days prior to leukapheresis;
    • Venetoclax within 4 days prior to leukapheresis;
    • Idelalisib or duvelisib within 2 days prior to leukapheresis;
    • Lenalidomide or acalabrutinib within 1 day prior to leukapheresis;
    • Experimental agents, including off-label use of approved drugs, within 4 weeks prior to leukapheresis unless progression is documented on the experimental therapy and at least 3 halflives have elapsed prior to leukapheresis.
  • Uncontrolled medical, psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol, as judged by the Investigator; or subject unwillingness or inability to follow the procedures required in the protocol.
  • Progressive vascular tumor invasion, thrombosis, or embolism.
  • Venous thrombosis or embolism requiring treatment but not managed on a stable regimen of anticoagulation.
  • For subjects in the venetoclax + JCAR017 combination cohorts only, concomitant treatment with CYP3A moderate/strong inducers or moderate/strong inhibitors which cannot be discontinued.
Biologic/Vaccine, Administration of antineoplastic agent, Drug therapy, Immunotherapy for cancer
Cancer, Chronic lymphocytic leukemia, Leukemia, Lymphoma, Non-Hodgkin's lymphoma
Biological therapy for cancer, Cancer treatment, Chronic lymphoid leukemia, disease, Hematopoietic system, Malignant lymphoma - small lymphocytic, Medical Oncology, Cellular therapy
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Mayo Clinic — Rochester, MN

A Pilot Study Evaluating the Feasibility of Memantine in Reducing Cognitive Impairment in Pediatric Patients After Radiation Therapy for Central Nervous System Tumors

A Study to Evaluate the Feasibility of Memantine in Reducing Cognitive Impairment in Pediatric Patients After Radiation Therapy for Central Nervous System Tumors

Nadia Laack
All
4 years to 18 years old
ERROR
This study is NOT accepting healthy volunteers
0000-100836-P01-RST
19-004245
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Inclusion Criteria:

  • Age ≥ 4 years to ≤ 18 years old.
  • Receiving intracranial radiation for a primary CNS malignancy.
  • Histological or radiologic confirmation of intracranial disease.
  • Able to use the computer for CogState assessment battery.
  • Serum creatinine and total bilirubin obtained ≤ 35 days prior to study entry, with adequate kidney and liver function defined as follows:
    • Normal serum creatinine per institutional normal limits;
    • Total bilirubin ≤ 1.5 x upper limit of normal (ULN) OR Direct bilirubin ≤ ULN for patients with total bilirubin levels > 1.5 x ULN, Aspartate transaminase (AST) AND alanine transaminase (ALT) ≤ 2.5 x ULN.
  • Provide informed consent if over age 18, or provide assent with consent from parent or legal guardian if age 7-17.
  • Negative pregnancy test done ≤ 7 days prior to registration, for women of childbearing potential only. Patients capable of childbearing must use adequate contraception.


Exclusion Criteria:

  • Patients with WHO Grade IV astrocytoma or glioblastoma tumors.
    • Note: A patient with Grade IV tumors of other histology can participate in the study if they meet all other criteria.
  • Any prior intracranial radiation.
  • Any contraindication or allergy to memantine.
  • Use of short-acting benzodiazepines (may excite lethargy/dizziness with memantine).
    • Note: occasional use as a sleep aid or as needed  for anxiety or nausea is allowed.
  • Intractable seizures while on adequate anticonvulsant therapy, defined as more than one seizure per month for the past 2 months.
  • 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.
  • 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 situations that would limit compliance with study requirements.

 

Drug, Drug therapy, Radiation oncology AND/OR radiotherapy, Radiotherapy to head
Brain tumor, Cancer, Cognitive impairment, Pediatric brain tumor
Cancer treatment, Impaired cognition, Malignant neoplasm of central nervous system, Medical Oncology, Memantine, Nervous system, Radiation therapy, memantine
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Mayo Clinic — Rochester, MN

A Comparison of Acute Toxicities between Patients Treated with Protons or Intensity-Modulated Radiation Therapy for Post-Operative Treatment of Endometrial or Cervical Cancers

Comparison of Acute Toxicities Between Patients Treated With Protons or Intensity Modulated Radiation Therapy After Surgery for the Treatment of Endometrial or Cervical Cancer

Allison Garda
Female
18 years and over
Not Applicable
This study is NOT accepting healthy volunteers
0000-100837-P01-RST
19-004792
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Inclusion Criteria:


- Histologically confirmed diagnosis of cervical or endometrial cancer

- Must have undergone an open or robotic hysterectomy (total abdominal, vaginal,
radical, or total laparoscopic) for carcinoma of the cervix or endometrium

- History and physical prior to registration

- Documentation of history of:

- Smoking status

- Pelvic infection

- Pelvic inflammatory disease

- Endometriosis

- Planned to receive either proton or IMRT radiation treatment, with use of rectal
balloon, at an Institutional Review Board (IRB)-approved Mayo Clinic site

- Plan for RT to pelvis with or without para-aortic lymph node irradiation

- If received high-dose chemotherapy prior to registration, last dose must have been
given >= 21 days prior to start of RT

- Complete blood count (CBC) performed within 21 days prior to registration

- Computed tomography (CT), magnetic resonance imaging (MRI), positron emission
tomography (PET)/CT, or PET/MRI for staging before registration; may be pre-operative
(op) or post-op

- Eastern Cooperative Oncology Group (ECOG) performance score 0-2

- Provide written informed consent

- Willing to complete quality of life (QOL) questionnaires


Exclusion Criteria:


- Receiving external beam boost dose during RT

- Distant metastases

- Gross disease at time of RT

- Histology of endometrial stromal sarcoma, leiomyosarcoma, melanoma or small cell
carcinomas

- Patients who exceed the weight/size limits of the treatment table

- Patients with active and/or inflammatory irritable bowel disease

- Positive or close surgical margins (=< 3 mm)

- Prior RT to the pelvis

- Planned to receive inguinal node RT

- Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects

- Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease
Control and Prevention (CDC) definition; note that human immunodeficiency virus (HIV)
testing is not required for entry into this protocol. The need to exclude patients
with AIDS from this protocol is necessary because the treatments involved in this
protocol may be immunosuppressive

- Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free
for a minimum of 3 years

- Severe, active co-morbidity defined as follows:

- Unstable angina and/or congestive heart failure requiring hospitalization within
the last 6 months

- Transmural myocardial infarction within the last 6 months

- Acute bacterial or fungal infection requiring intravenous antibiotics at the time
of registration

- Other major medical illness which requires hospitalization or precludes study therapy
at the time of registration

- Patients unwilling to have rectal balloon placed on a daily basis during RT

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Eligibility last updated 3/28/23. Questions regarding updates should be directed to the study team contact.

Behavioral, Radiation, Other
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A Randomized Phase III Study of the Addition of Venetoclax to Ibrutinib and Obinutuzumab Versus Ibrutinib and Obinutuzumab in Untreated Younger Patients With Chronic Lymphocytic Leukemia (CLL)

A Study Comparing Ibrutinib and Obinutuzumab With or Without Venetoclax in Treating Patients with Chronic Lymphocytic Leukemia

Mohammad Ranginwala
All
18 years to 69 years old
Phase 3
This study is NOT accepting healthy volunteers
0000-100848-P01-MAIJ
19-000455
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Inclusion Criteria:
 

Diagnosis of CLL according to the National Cancer Institute (NCI)/International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria or small lymphocytic lymphoma (SLL) according to the World Health Organization (WHO) criteria. This includes previous documentation of: 

  • Biopsy-proven small lymphocytic lymphoma; OR 
  • Diagnosis of CLL according to the NCI/IWCLL criteria as evidenced by all of the following: 
    • Peripheral blood lymphocyte count of greater than 5 x10^9/L;
    • Immunophenotype consistent with CLL defined as: 
      • The predominant population of lymphocytes share both B-cell antigens (CD19, CD20 [typically dim expression], or CD23) as well as CD5 in the absence of other pan-T-cell markers (CD3, CD2, etc.);
      • Clonality as evidenced by kappa or lambda light chain restriction (typically dim immunoglobulin expression).
    • Negative fluorescent in situ hybridization (FISH) analysis for t(11;14)(IgH/CCND1) on peripheral blood or tissue biopsy (e.g., marrow aspirate) or negative immunohistochemical stains for cyclin D1 staining on involved tissue biopsy (e.g., marrow aspirate or lymph node biopsy.
  • No prior chemotherapy, BTK inhibitor therapy, venetoclax, small molecule signaling inhibitor, or monoclonal anti-body therapy for treatment of CLL or SLL. 
  • Has met at least one of the following indications for treatment: 
    • Evidence of progressive marrow failure as manifested by the development of worsening anemia (hemoglobin [Hg] < 11 g/dl) and/or thrombocytopenia (platelets < 100 x 10^9/L);
    • Symptomatic or progressive lymphadenopathy, splenomegaly, or hepatomegaly; 
    • One or more of the following disease-related symptoms: 
      • Weight loss >= 10% within the previous 6 months;
      • Grade 2 or 3 fatigue attributed to CLL;
      • Fevers > 100.5 degree Fahrenheit (F) for 2 weeks without evidence of infection;
      • Clinically significant night sweats without evidence of infection.
    • Progressive lymphocytosis (not due to the effects of corticosteroids) with an increase of > 50% over a two-month period or an anticipated doubling time of less than six months.
  • Eastern Cooperative Oncology Group (ECOG) performance status between 0-2
    •Life expectancy of >= 12 months. 
  • No deletion of 17p13 on cytogenetic analysis by FISH. 
  • Glomerular filtration rate (GFR) > 40 mL/minute as calculated by the Cockcroft-Gault Formula (obtained =< 14 days prior to registration).
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) unless due to Gilbert's disease. For those with a total bilirubin > 1.5 x ULN, a direct bilirubin should be performed and must be < 1.5 mg/dL for Gilbert's to be diagnosed (obtained =< 14 days prior to registration).
  • Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST])/serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 3.0 x the institutional ULN (obtained =< 14 days prior to registration).
  • Prothrombin time (PT)/international normalized ratio (INR) < 1.5 ULN and partial thromboplastin time (PTT) (activated partial thromboplastin time [aPTT]) < 1.5 x ULN (obtained =< 14 days prior to registration). 
    • NOTE: If value is higher due to hepatic involvement by CLL, patient is eligible. 
  • No active hemolytic anemia requiring immunosuppressive therapy or other pharmacologic treatment. Patients who have a positive Coombs test but no evidence of hemolysis are NOT excluded from participation.
  • No current use of corticosteroids. EXCEPTION: Low doses of steroids (< 10 mg of prednisone or equivalent dose of other steroid) used for treatment of non-hematologic medical condition (e.g. chronic adrenal insufficiency) is permitted.
  • No previous autoimmune complications (e.g. autoimmune hemolytic anemia or immune thrombocytopenia) that have developed since the initial diagnosis of CLL and have required treatment with high dose corticosteroids (e.g., equivalent of > 20 mg/day of prednisone), monoclonal antibody based therapy, or chemotherapy. Prior use of corticosteroids for reasons other than treatment of autoimmune complications is allowed.
  • No other active primary malignancy (other than non-melanomatous skin cancer or carcinoma in situ of the cervix) requiring treatment or limiting expected survival to =< 2 years. 
    • NOTE: If there is a history of prior malignancy, the patient must not currently be receiving other specific treatment (other than hormonal therapy for their cancer). 
  • Able to adhere to the study visit schedule and other protocol requirements.
  • No major surgery within 4 weeks (28 days) of first dose of study drug or minor surgery within 3 days of first dose of study drug. 
  • No radiation therapy =< 4 weeks prior to registration. 
  • Patients who are human immunodeficiency virus positive (HIV+) with undetectable HIV viral load are eligible provided they meet all other protocol criteria for participation and are not being treated with protease inhibitors or any non-nucleoside reverse transcriptase inhibitors (NNRTI) that are CYP3A4 inducers; if being treated for HIV, patients should be receiving an alternative antiretroviral therapy (ART) that is not a CYP3A inhibitor. 
  • Patients must not have any of the following conditions: 
    • Congestive heart failure or New York Heart Association Functional Classification III or IV congestive heart failure; 
    • History of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to registration;
    • Recent infections requiring systemic treatment; need to have completed anti-biotic therapy > 14 days before the first dose of study drug; 
    • Cerebral vascular accident or intracranial bleed within the last 6 months
      •Infection with known chronic, active hepatitis C; 
    • Serologic status reflecting active hepatitis B or C infection. Patients with hepatitis B or C infection may be eligible if viral loads are undetectable. Patients may be on suppressive therapy.
  • Patients are not eligible if they require treatment with a strong cytochrome P450 (CYP) 3A inhibitor.
  • Patients may not have received the following within 7 days prior to the first dose of study drug: 
    • Steroid therapy for anti-neoplastic intent;
    • Strong and Moderate CYP3A inhibitors; 
    • Strong and Moderate CYP3A inducers.
  • Patients may not be on any other investigational agents.
  • Patients may not have received warfarin or another vitamin K antagonist in the preceding 30 days. 
  • Women must not be pregnant or breast-feeding since this study involves investigational agents whose genotoxic, mutagenic, and teratogenic effects on the developing fetus and newborn are unknown. All females of childbearing potential must have a blood test within 2 weeks 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: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (e.g., has had menses at any time in the preceding 24 consecutive months. 
  • Women of childbearing potential and sexually active males must be strongly advised to use accepted and highly effective method(s) of contraception or to abstain from sexual intercourse for the duration of their participation in the study and for: 
    • 18 months after the last dose of obinutuzumab; 
    • 90 days after the last dose of ibrutinib; and 
    • 30 days after the last dose of venetoclax Male subjects must also agree to refrain from sperm donation until 90 days after the last dose of protocol treatment.
  • Patient must be able to swallow capsules and not have the following conditions: 
    • Disease significantly affecting gastrointestinal function;
    • Resection of the stomach or small bowel;
    • Symptomatic inflammatory bowel disease; 
    • Ulcerative colitis; 
    • Partial or complete bowel obstruction. 
  • Patient must not be on any other systemic immunosuppressant therapy other than corticosteroids within 28 days of the first dose of study drug. 
  • Patient must not be vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug.
  • Patient must not have any known bleeding disorders (e.g., von Willebrand's disease) or hemophilia. 
  • Patient must not have currently active, clinically significant hepatic impairment (>= moderate hepatic impairment according to the NCI/Child Pugh classification. 
  • Patient must undergo assessment with Timed Up and Go (TUG) test. 
  • Patient must be able to receive xanthine oxidase inhibitor or rasburicase for tumor lysis syndrome (TLS) prophylaxis.
Biologic/Vaccine, Drug, Other, Administration of antineoplastic agent, Chemotherapy, Drug therapy, Immunotherapy for cancer
Cancer, Chronic lymphocytic leukemia, Leukemia, Lymphoma
4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)-2-(1H-pyrrolo(2,3-b)pyridin-5-yloxy)benzamide, Afutuzumab, Biological therapy for cancer, Cancer treatment, Chemotherapy, Chronic lymphoid leukemia, disease, Hematopoietic system, Ibrutinib [USAN:INN], Malignant lymphoma - small lymphocytic, Medical Oncology, Targeted drug therapy, ibrutinib, obinutuzumab, venetoclax
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A Randomized Phase III Study of the Addition of Venetoclax to Ibrutinib and Obinutuzumab Versus Ibrutinib and Obinutuzumab in Untreated Younger Patients With Chronic Lymphocytic Leukemia (CLL)

A Study Comparing Ibrutinib and Obinutuzumab With or Without Venetoclax in Treating Patients with Chronic Lymphocytic Leukemia

Neil Kay
All
18 years to 69 years old
Phase 3
This study is NOT accepting healthy volunteers
0000-100848-P01-RST
19-000455
Show full eligibility criteria
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Inclusion Criteria:
 

Diagnosis of CLL according to the National Cancer Institute (NCI)/International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria or small lymphocytic lymphoma (SLL) according to the World Health Organization (WHO) criteria. This includes previous documentation of: 

  • Biopsy-proven small lymphocytic lymphoma; OR 
  • Diagnosis of CLL according to the NCI/IWCLL criteria as evidenced by all of the following: 
    • Peripheral blood lymphocyte count of greater than 5 x10^9/L;
    • Immunophenotype consistent with CLL defined as: 
      • The predominant population of lymphocytes share both B-cell antigens (CD19, CD20 [typically dim expression], or CD23) as well as CD5 in the absence of other pan-T-cell markers (CD3, CD2, etc.);
      • Clonality as evidenced by kappa or lambda light chain restriction (typically dim immunoglobulin expression).
    • Negative fluorescent in situ hybridization (FISH) analysis for t(11;14)(IgH/CCND1) on peripheral blood or tissue biopsy (e.g., marrow aspirate) or negative immunohistochemical stains for cyclin D1 staining on involved tissue biopsy (e.g., marrow aspirate or lymph node biopsy.
  • No prior chemotherapy, BTK inhibitor therapy, venetoclax, small molecule signaling inhibitor, or monoclonal anti-body therapy for treatment of CLL or SLL. 
  • Has met at least one of the following indications for treatment: 
    • Evidence of progressive marrow failure as manifested by the development of worsening anemia (hemoglobin [Hg] < 11 g/dl) and/or thrombocytopenia (platelets < 100 x 10^9/L);
    • Symptomatic or progressive lymphadenopathy, splenomegaly, or hepatomegaly; 
    • One or more of the following disease-related symptoms: 
      • Weight loss >= 10% within the previous 6 months;
      • Grade 2 or 3 fatigue attributed to CLL;
      • Fevers > 100.5 degree Fahrenheit (F) for 2 weeks without evidence of infection;
      • Clinically significant night sweats without evidence of infection.
    • Progressive lymphocytosis (not due to the effects of corticosteroids) with an increase of > 50% over a two-month period or an anticipated doubling time of less than six months.
  • Eastern Cooperative Oncology Group (ECOG) performance status between 0-2
    •Life expectancy of >= 12 months. 
  • No deletion of 17p13 on cytogenetic analysis by FISH. 
  • Glomerular filtration rate (GFR) > 40 mL/minute as calculated by the Cockcroft-Gault Formula (obtained =< 14 days prior to registration).
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) unless due to Gilbert's disease. For those with a total bilirubin > 1.5 x ULN, a direct bilirubin should be performed and must be < 1.5 mg/dL for Gilbert's to be diagnosed (obtained =< 14 days prior to registration).
  • Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST])/serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 3.0 x the institutional ULN (obtained =< 14 days prior to registration).
  • Prothrombin time (PT)/international normalized ratio (INR) < 1.5 ULN and partial thromboplastin time (PTT) (activated partial thromboplastin time [aPTT]) < 1.5 x ULN (obtained =< 14 days prior to registration). 
    • NOTE: If value is higher due to hepatic involvement by CLL, patient is eligible. 
  • No active hemolytic anemia requiring immunosuppressive therapy or other pharmacologic treatment. Patients who have a positive Coombs test but no evidence of hemolysis are NOT excluded from participation.
  • No current use of corticosteroids. EXCEPTION: Low doses of steroids (< 10 mg of prednisone or equivalent dose of other steroid) used for treatment of non-hematologic medical condition (e.g. chronic adrenal insufficiency) is permitted.
  • No previous autoimmune complications (e.g. autoimmune hemolytic anemia or immune thrombocytopenia) that have developed since the initial diagnosis of CLL and have required treatment with high dose corticosteroids (e.g., equivalent of > 20 mg/day of prednisone), monoclonal antibody based therapy, or chemotherapy. Prior use of corticosteroids for reasons other than treatment of autoimmune complications is allowed.
  • No other active primary malignancy (other than non-melanomatous skin cancer or carcinoma in situ of the cervix) requiring treatment or limiting expected survival to =< 2 years. 
    • NOTE: If there is a history of prior malignancy, the patient must not currently be receiving other specific treatment (other than hormonal therapy for their cancer). 
  • Able to adhere to the study visit schedule and other protocol requirements.
  • No major surgery within 4 weeks (28 days) of first dose of study drug or minor surgery within 3 days of first dose of study drug. 
  • No radiation therapy =< 4 weeks prior to registration. 
  • Patients who are human immunodeficiency virus positive (HIV+) with undetectable HIV viral load are eligible provided they meet all other protocol criteria for participation and are not being treated with protease inhibitors or any non-nucleoside reverse transcriptase inhibitors (NNRTI) that are CYP3A4 inducers; if being treated for HIV, patients should be receiving an alternative antiretroviral therapy (ART) that is not a CYP3A inhibitor. 
  • Patients must not have any of the following conditions: 
    • Congestive heart failure or New York Heart Association Functional Classification III or IV congestive heart failure; 
    • History of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to registration;
    • Recent infections requiring systemic treatment; need to have completed anti-biotic therapy > 14 days before the first dose of study drug; 
    • Cerebral vascular accident or intracranial bleed within the last 6 months
      •Infection with known chronic, active hepatitis C; 
    • Serologic status reflecting active hepatitis B or C infection. Patients with hepatitis B or C infection may be eligible if viral loads are undetectable. Patients may be on suppressive therapy.
  • Patients are not eligible if they require treatment with a strong cytochrome P450 (CYP) 3A inhibitor.
  • Patients may not have received the following within 7 days prior to the first dose of study drug: 
    • Steroid therapy for anti-neoplastic intent;
    • Strong and Moderate CYP3A inhibitors; 
    • Strong and Moderate CYP3A inducers.
  • Patients may not be on any other investigational agents.
  • Patients may not have received warfarin or another vitamin K antagonist in the preceding 30 days. 
  • Women must not be pregnant or breast-feeding since this study involves investigational agents whose genotoxic, mutagenic, and teratogenic effects on the developing fetus and newborn are unknown. All females of childbearing potential must have a blood test within 2 weeks 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: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (e.g., has had menses at any time in the preceding 24 consecutive months. 
  • Women of childbearing potential and sexually active males must be strongly advised to use accepted and highly effective method(s) of contraception or to abstain from sexual intercourse for the duration of their participation in the study and for: 
    • 18 months after the last dose of obinutuzumab; 
    • 90 days after the last dose of ibrutinib; and 
    • 30 days after the last dose of venetoclax Male subjects must also agree to refrain from sperm donation until 90 days after the last dose of protocol treatment.
  • Patient must be able to swallow capsules and not have the following conditions: 
    • Disease significantly affecting gastrointestinal function;
    • Resection of the stomach or small bowel;
    • Symptomatic inflammatory bowel disease; 
    • Ulcerative colitis; 
    • Partial or complete bowel obstruction. 
  • Patient must not be on any other systemic immunosuppressant therapy other than corticosteroids within 28 days of the first dose of study drug. 
  • Patient must not be vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug.
  • Patient must not have any known bleeding disorders (e.g., von Willebrand's disease) or hemophilia. 
  • Patient must not have currently active, clinically significant hepatic impairment (>= moderate hepatic impairment according to the NCI/Child Pugh classification. 
  • Patient must undergo assessment with Timed Up and Go (TUG) test. 
  • Patient must be able to receive xanthine oxidase inhibitor or rasburicase for tumor lysis syndrome (TLS) prophylaxis.
Biologic/Vaccine, Drug, Other, Administration of antineoplastic agent, Chemotherapy, Drug therapy, Immunotherapy for cancer
Cancer, Chronic lymphocytic leukemia, Leukemia, Lymphoma
4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)-2-(1H-pyrrolo(2,3-b)pyridin-5-yloxy)benzamide, Afutuzumab, Biological therapy for cancer, Cancer treatment, Chemotherapy, Chronic lymphoid leukemia, disease, Hematopoietic system, Ibrutinib [USAN:INN], Malignant lymphoma - small lymphocytic, Medical Oncology, Targeted drug therapy, ibrutinib, obinutuzumab, venetoclax
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Phase 1-2 Trial of Systemically Administered VSV-IFNβ-NIS in Combination with Checkpoint Inhibitor Therapy in Patients with Selected Solid Tumors

A Study to Evaluate the Safety, Tolerability, and Determine the Optimal Dose for the Expansion Cohorts of VSV-IFNβ-NIS in Combination with Pembrolizumab in Patients with Refractory Solid Tumors

Patrick McGarrah
All
18 years and over
Phase 1/2
This study is NOT accepting healthy volunteers
0000-100858-P01-RST
18-011203
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Inclusion Criteria:

  • Age ≥ 18 years on day of signing informed consent.
  • Histologically confirmed diagnosis of:
    • Part A: advanced and/or metastatic solid tumor for which no existing options are felt to provide clinical benefit;
    • Part B: advanced and/or metastatic NSCLC in which radiological progression has been demonstrated during therapy with a PD-(L)1 immune checkpoint inhibitor, and for which no existing options are felt to provide clinical benefit;
    • Part C: advanced and/or metastatic NEC (neuroendocrine carcinoma based on histopathology according to WHO criteria. Patients with small cell carcinoma, large cell neuroendocrine carcinoma, and neuroendocrine carcinoma not otherwise specified, of any primary organ are eligible [Nagtegaal 2020]) in which radiological progression has been demonstrated during therapy with a PD-(L)1 immune checkpoint inhibitor, and for which no existing options are felt to provide clinical benefit.
  • Measurable disease based on RECIST 1.1 (except the first 3 patients in the safety run-in).
    • NOTE: Liver lesions that have been previously embolized (bland embolization, chemo- or radio-embolization) or have undergone percutaneous thermoablation are not eligible as target lesions.
  • Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
  • Life expectancy of > 3 months if not on active anti-cancer therapy.
  • Willingness to provide biological samples required for the duration of the study including a fresh tumor biopsy sample.
  • Adequate organ function defined as the following laboratory values obtained ≤ 14 days prior to registration:
  • Hematological
    • Absolute neutrophil count (ANC) ≥ 1500/mcL;
    • Platelets ≥ 100 000/mcL;
    • Hemoglobin ≥ 9 g/dL.
  • Renal
    • Serum creatinine ≤ 2.0 x ULN OR Measured or calculated creatinine clearance (CL)(per CKD-EPI) ≥ 40 mL/min for patients with creatinine levels > 2.0 x ULN.
  • Hepatic
    • Direct bilirubin ≤ 1.5 x ULN;
    • Aspartate aminotransferase (AST) ≤ 2.5 x ULN;
    • Alanine aminotransferase (ALT) ≤ 2.5 x ULN Not exceeding Class A overall or B7 for HCC.
  • Negative pregnancy test for female patients of childbearing potential.
  • Absence of active Central Nervous System (CNS) involvement.
    • NOTE: Pre-enrollment imaging of asymptomatic patients not mandatory.
  • Ability to provide written informed consent.


Exclusion Criteria:
 

  • Availability of and patient acceptance of curative therapy.
  • Recent or ongoing serious infection, including:
    • Any active Grade 3 or higher per the National Institute of Cancer Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE, v5.0) viral, bacterial, or fungal infection within 2 weeks of registration;
    • Known seropositivity for or active infection by the human immunodeficiency virus (HIV);
    • Acute hepatitis B or acute hepatitis C (HCV). Patients with chronic hepatitis B or HCV may be enrolled provided their liver function is adequate as per inclusion criteria;
    • Known history of active TB (bacillus tuberculosis).
  • Any serious health condition, which, in the opinion of the investigator, would place the patient at undue risk from the study, including uncontrolled hypertension and/or diabetes, clinically significant pulmonary disease (e.g., chronic obstructive pulmonary disease requiring hospitalization within 3 months) or neurological disorder (e.g., seizure disorder active within 3 months).
  • Prior therapy within the following timeframe before the planned start of study treatment as follows:
    • Chemotherapy, small molecule inhibitors, radiation, interventional radiology (IR) procedure, and/or other investigational agent: ≤ 3 weeks or 5 half-lives, whichever is shorter;
    • Other monoclonal antibodies, antibody-drug conjugates, radioimmunoconjugates, or experimental therapies: ≤ 4 weeks (≤ 3 weeks with documented disease progression),
  • New York Heart Association (NYHA) classification III or IV, known symptomatic coronary artery disease, or symptoms of coronary artery disease on systems review, or known cardiac arrhythmias (atrial fibrillation or SVT).
  • Any known or suspected active organ-threatening autoimmune disease, such as inflammatory bowel disease, autoimmune hepatitis, lupus, or pneumonitis, with the exception of hypothyroidism and type 1 diabetes that are controlled with treatment.
  • Immunodeficiency or immunosuppression, including systemic corticosteroids at > 10mg/day prednisone or equivalent within 1 week prior to planned start of study treatment.
  • History of severe immune-mediated adverse reaction to immune CPIs.
  • Toxicities from previous therapies that have not resolved to a grade 1 or less.
  • History of non-infectious pneumonitis that required steroids, or current pneumonitis.
  • High volume disease, as assessed clinically via parameters such as radiologic impression and tumor markers or lactate dehydrogenase (LDH).
  • Portal vein thrombosis involving more than intrahepatic portal vein branches: thrombosis of the right or left portal vein branch or the bifurcation, partial or complete obstruction of the portal vein trunk.
  • Known concurrent malignancy that is progressing or requires active treatment.
    • EXCEPTIONS: basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in-situ cervical cancer that has been treated with curative intent, prostate cancer confined to the prostate gland with Gleason score < 6 or PSA < 1, as well as any stage I cancer treated with curative intent or any prior cancer with a disease-free interval of ≥ 3 years.
  • Other concurrent anti-cancer therapy (chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational (used for a non-Food and Drug Administration (FDA) approved indication and in the context of a research investigation)).
  • Has received a live vaccine within 30 days of planned start of study treatment. Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; intranasal influenza vaccines (e.g., Flu-Mist® are live attenuated vaccines and are NOT allowed.
  • Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:
    • Pregnant women or women of reproductive ability who are unwilling to use highly effective contraception;
    • Nursing women;
    • Men who are unwilling to use a condom (even if they have undergone a prior vasectomy) while having intercourse with any woman, while taking the drug and for 4 weeks after stopping treatment.

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

 

Biologic/Vaccine, Drug, Administration of antineoplastic agent, Combination therapy, Drug therapy, Immunotherapy for cancer, Oncolytic virus therapy
Cancer, Hepatocellular carcinoma, Liver cancer, Lung cancer, Non-small cell lung cancer, Recurrent cancer
Biological therapy for cancer, Cancer treatment, Digestive system, Liver cell carcinoma, Medical Oncology, Non-small cell lung cancer, Pembrolizumab [USAN:INN], Respiratory system, Virotherapy, pembrolizumab
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MC19C1, Rose Geranium in Sesame Oil Nasal Spray as an Agent to Improve Symptoms of Nasal Vestibulitis: A Phase III Double Blinded Randomized Controlled Trial (MC19C1)

Rose Geranium in Sesame Oil Nasal Spray for the Improvement of Nasal Vestibulitis Symptoms in Cancer Patients Receiving Chemotherapy

Charles Loprinzi
All
18 years and over
Phase 3
This study is NOT accepting healthy volunteers
0000-100863-P01-RST
19-006677
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Registration
•Inclusion Criteria

  • Age ≥ 18 years.
  • Diagnosed with cancer and receiving chemotherapy.
  • Able to provide informed consent.
  • Willingness to complete questionnaires.
  • ECOG Performance Status (PS) 0, 1, 2.
  • One or more of the following nasal symptoms for which the patient reports they would appreciate treatment. Symptoms must have started after the initiation of systemic, antineoplastic therapies, be attributed to the systemic, antineoplastic therapies, and symptoms must be reported  as being moderate (corresponding to a score of 2) or worse on a scale from mild (1) to very severe (4) on at least one of the items below.
  • Dryness;
  • Discomfort/Pain;
  • Bleeding;
  • Scabbing;
  • Sores.

 Registration


Exclusion Criteria:

  • Predisposition to epistaxis prior to the initiation of cancer-directed therapy (more than once a month over the previous year).
  • Planned initiation or continuation of any topical nasal treatment other than the studied nasal spray,( such as nasal steroids, Ayr nasal gel, Neosporin ointment or nasal administration of petroleum jelly).  Taking Imitrex for migraines is acceptable.
  • Previous exposure to rose geranium in sesame oil nasal spray.
  • Concurrent upper respiratory tract infection.
  • History of allergic or other adverse reactions to sesame oil or essential rose geranium oil.
  • Any other reason that the study clinician or investigator feels precludes safe or appropriate inclusion in this study.

Re-Registration:

  • The patient will be un-blinded and determined to have been on the saline arm, when initially randomized.
Drug
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EA9171, BLAST MRD CML 1 Trial: BLockade of PD-1 Added to Standard Therapy to Target Measurable Residual Disease (MRD) in Chronic Myeloid Leukemia (CML) - A Phase II Study of Adding the Anti-PD-1 Pembrolizumab to Tyrosine Kinase Inhibitors in Patients With CML and Persistently Detectable MRD

A Study to Evaluate Pembrolizumab and Dasatinib, Imatinib Mesylate, or Nilotinib in Treating Patients with Chronic Myeloid Leukemia and Persistently- Detectable Minimal Residual Disease

Mark Litzow
All
18 years and over
Phase 2
This study is NOT accepting healthy volunteers
0000-100877-P01-RST
19-002029
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Inclusion Criteria:
 

PREREGISTRATION (STEP 0)

  • Age ≥ 18 years.
  • Patient has pathologically-confirmed chronic phase-CML one of the following the following criteria:
    • Patient has been in MMR (i.e. MR3) with detectable BCR/ABL transcript by a standard RQ-PCR assay for at least 12 months from the first documentation of the MMR;
    • Has been in MMR (i.e. MR3) but still has detectable BCR/ABL transcript by a standard RQ-PCR assay for at least 12 months from the first documentation of the MMR;
    • Up to two values above MMR (0.1%) are allowed in the last 12 months long as there was no change in the type or dose of TKI in last 6 months, none of the lab values were higher than CCR (1% or more) in the last 12 months, and all values in the last 6 months were at MMR or deeper;
    • Patient has not maintained MR4.5 (CMR) within the time of initiation of TKI therapy and pre-registration. Patient can have intermittent values of CMR (at or below MR4.5). However the patient has to have detectable disease (i.e. cannot be in CMR) in the last 2 assessments before pre-registration; AND 
    • Patient must have a diagnosis of chronic phase-CML has been confirmed by a bone marrow aspirate and/or biopsy with ≤ 10 % myeloid blasts (i.e., no accelerated or blast phase) within 21after consenting and pre -registration to step 0 and MMR status and BCR/ABL results meets the criteria outlined above.
      • NOTE: Please be aware of the required timeframe restrictions. Patients are required to enroll on Step 1 within 21 days from the date of consenting (step 0, pre-registration)
  • Patients with diagnoses of accelerated or blast phase CML are not eligible.
  • Patient has been on TKI therapy (first and/or second line) for at least 2 years (starting from when first TKI was initiated) prior to pre-registration:
    • Allowed TKIs include:
      • • Dasatinib: 50 – 180 mg per day;
      • • Imatinib: 200 – 800 mg per day;
      • • Nilotinib: 200 – 400 mg every 12-24 hours.
  • Patients must have been on a stable dose of the current TKI for the last 3 months prior to pre-registration. For patients with two values of above MMR (0.1%) within the last 12 months, patient must have been on stable dose of the current TKI for the last 6 months prior to pre-registration.
  • For patients who are on second line TKI, patient has been on second line TKI for at least a year from start date of second line TKI.
  • Patient must not have received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
  • Patients must not have received a prior allogeneic transplant.

REGISTRATION TO TREATMENT (STEP 1)

  • Institution has received central BCR-ABL test results confirming MRD positive status and bone marrow aspirate and/or biopsy has confirmed chronic phase CML (i.e. no accelerated or blast phase CML) Bone marrow showing morphologic remission is acceptable.
  • Patients have an ECOG Performance Status of 0-2.
  • Diagnosis of chronic phase-CML must had been confirmed by a bone marrow aspirate and/or biopsy with ≤ 10 % myeloid blasts (i.e., no accelerated or blast phase) within 21 days prior to registration to step 1. Bone marrow aspirate and/or biopsy showing morphologic remission is acceptable. MMR and BCR/ABL status meets the criteria defined above.
  • No active hemolytic anemia requiring immunosuppressive therapy or other pharmacologic treatment. Patients who have a positive Coombs test but no evidence of hemolysis are NOT excluded from participation
  • No current use of corticosteroids from time of consent to registration.
    • EXCEPTION: Low doses of steroids (< 10 mg of prednisone or equivalent dose of other steroid) used for treatment of non-hematologic medical condition (e.g., chronic adrenal insufficiency) is permitted.
  • No other active primary malignancy (other than non-melanomatous skin cancer or carcinoma in situ of the cervix) requiring treatment or limiting expected survival to ≤ 2 years.
    • NOTE: If there is a history of prior malignancy, they must not be receiving other specific treatment (other than hormonal therapy for their cancer).
  • Women must not be pregnant or breastfeeding due to the potential for congenital abnormalities and of harm to nursing infants due to the treatment regimens used. Patients must also not expect to conceive or father children from the time of registration, while on study treatment, and continue for 120 days after the last dose of study treatment
    • All females of childbearing potential must have a negative urine or serum pregnancy test conducted within 14 days prior to registration to rule out pregnancy. A urine or serum pregnancy test must be repeated within 72 hours prior to receiving the first dose of pembrolizumab if the test done for eligibility/registration to step 1 is done outside of this 72 hour window. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required;
    • A female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point; 2)has not undergone a hysterectomy or bilateral oophorectomy; or 3) 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).
    • Female of child bearing potential? ______ (Yes or No)
      • Date of urine/serum study: ___________
  • Women of childbearing potential and sexually active males must use accepted and effective method(s) of contraception or to abstain from sex from time of registration, while on study treatment, and continue for 120 days after the last dose of study treatment. 
  • Patient may not be currently participating and receiving study therapy or have participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of registration.
  • Patient must not have a diagnosis of immunodeficiency or be receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of treatment.
  • Patient must not have a known history of active TB (Bacillus Tuberculosis).
  • Patient must not have a history of hypersensitivity to pembrolizumab or any of its excipients.
  • Patient must not have received a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to registration or have not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
  • Patient must not have had prior chemotherapy, targeted small molecule therapy (aside from imatinib, dasatinib, or nilotinib), or radiation therapy within 2 weeks prior to registration to Step 1. Patients also must have recovered from all adverse events due to a previously administered agent.
    • NOTE: Patients with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
    • NOTE: 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).
  • Patients who have received major surgery must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
  • Patient must not have a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
  • Patient must not have known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of protocol 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 protocol treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
  • Patient must not have 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 (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
  • Patient must not have known history of, or any evidence of active, non-infectious pneumonitis.
  • Patient must not have an active infection requiring systemic therapy.
  • Patient must not have 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.
  • Patient must not have known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • Patients who are Human Immunodeficiency Virus (HIV) positive are eligible if they have undetectable HIV viral load and CD4+ T-cell count ≥ 250/mm^3.
  • Patients with a known positive test for Hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection may be be enrolled if the viral load by PCR is undetectable with/without active treatment.
  • Patients must not have a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive).
  • Patient must not have received a live vaccine within 30 days of registration.
    • NOTE: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.
  • Patients must meet the following criteria with all screening labs performed within 14 days prior to registration:
    • Absolute neutrophil count (ANC) ≥ 1,500 /mcL
      • ANC: _________ Date of Test: _________
    • Platelet count ≥ 100,000 /mcL
      • Platelet:_______ Date of Test: _________
    • Hgb ≥ 9.0 g/dL OR ≥ 5.6 mmol/L without transfusion of EPO dependency
      • Hgb:__________ Date of Test:__________
    • Serum creatinine ≤ 1.5 X upper limit of normal (ULN) OR Creatinine clearance (per institutional standards) ≥ 60 mL/min for patient with creatinine levels > 1.5 X ULN
      • Serum creatinine ______________Date of Test: ________
    • or
      • Creatinine clearance: __________ Date of Test: ________
    • Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 X ULN
      • Bilirubin: __________ Institutional ULN: _________ Date of Test: __________
    • AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver metastases
      • ALT: _______ Institutional ULN: _________ Date of Test: _______
      • AST:_______  Institutional ULN:_________ Date of Test: _______
  • Patients should not be receiving concomitant strong CYP3A4 inducers or inhibitors ≤ 7 days prior to registration due to their potential to effect the activity or pharmacokinetics of study agents and/or QT interval prolongation toxicity. Should treatment with any of these agents be required, consult with study chair and reference Section 5.5 for TKI dose modifications related to concomitant drugs.
  • Patients who received prior allogeneic transplant are not eligible.

REGISTRATION TO TREATMENT (STEP 2)

  • Institution has received central BCR-ABL test results confirming MRD positive status at Cycle 16 or 17 or 18 following Step 1 treatment (MMR or deeper but not in CMR in the last two central lab checks before Step 2).
  • Patients have an ECOG Performance Status of 0-2.
  • No active hemolytic anemia requiring immunosuppressive therapy or other pharmacologic treatment. Patients who have a positive Coombs test but no evidence of hemolysis are NOT excluded from participation.
  • No current use of corticosteroids. EXCEPTION: Low doses of steroids (< 10 mg of prednisone or equivalent dose of other steroid) used for treatment of non-hematologic medical condition (e.g., chronic adrenal insufficiency) is permitted.
  • No other active primary malignancy (other than non-melanomatous skin cancer or carcinoma in situ of the cervix) requiring treatment or limiting expected survival to ≤ 2 years.
    • NOTE: If there is a history of prior malignancy, they must not be receiving other specific treatment (other than hormonal therapy for their cancer).
  • Patient must not have a diagnosis of immunodeficiency or be receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of treatment.
  • Patient must not have a known history of active TB (Bacillus Tuberculosis).
  • Patient must not have a history of hypersensitivity to pembrolizumab or any of its excipients.
  • Women must not be pregnant or breastfeeding due to the potential for congenital abnormalities and of harm to nursing infants due to the treatment regimens used. Patients must also not expect to conceive or father children from the time of registration, while on study treatment, and continue for 120 days after the last dose of study treatment
  • All females of childbearing potential must have a negative urine or serum pregnancy within 14 days prior to registration on step 2 to rule out a pregnancy. A urine or serum pregnancy test must be repeated within 72 hours prior to receiving the first dose of pembrolizumab on step 2 if the test done for eligibility/registration to step 2 is done outside of this 72 hour window. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  • A female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2)has not undergone a hysterectomy or bilateral oophorectomy; or3) 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).
  • Female of child bearing potential? ______ (Yes or No)
    • Date of urine/serum study: ___________
  • Women of childbearing potential and sexually active males must use accepted and effective method(s)of contraception or to abstain from sex from time of registration, while on study treatment, and continue for 120 days after the last dose of study treatment. (Refer to Section 5.6.2 for detailed information on contraception requirements while on this study).
  • Patient must not have known history of, or any evidence of active, non-infectious pneumonitis.
  • Patient must not have an active infection requiring systemic therapy.
  • Patient must not have 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.
  • Patients who are Human Immunodeficiency Virus (HIV) positive are eligible if they have undetectable HIV viral load and CD4+ T-cell count ≥ 250/mm^3.
  • Patient with a known positive test for Hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection might be enrolled if the viral load by PCR is undetectable with/without active treatment.
  • Patients must not have a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive).
  • Patient must not have received a live vaccine within 30 days of planned start of study therapy.
    • NOTE: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.
  • Patients must meet the following criteria with all screening labs performed within 14 days prior to registration:
  • Absolute neutrophil count (ANC) ≥ 1,500 /mcL
    • ANC:__________ Date of Test:__________
  • Platelet count ≥ 100,000 /mcL
    • Platelet:__________ Date of Test:__________
  • Hgb ≥ 9.0 g/dL OR ≥ 5.6 mmol/L without transfusion of EPO dependency
    • Hgb:__________ Date of Test:__________
  • Serum creatinine ≤ 1.5 X upper limit of normal (ULN) OR Creatinine clearance (per institutional standards) ≥ 60 mL/min for patient with creatinine levels > 1.5 X ULN
    • Serum creatinine ______________Date of Test:________
  • or
    • Creatinine clearance:__________ Date of Test:_________
  • Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 X ULN
    • Bilirubin:__________ Institutional ULN:_________ Date of Test:__________
  • AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver metastases
    • ALT: _______ Institutional ULN:_________ Date of Test: _______
    • AST: _______ Institutional ULN:_________ Date of Test: _______
  • Patients should not be receiving concomitant strong CYP3A4 inducers or inhibitors ≤ 7 days prior to registration due to their potential to effect the activity or pharmacokinetics of study agents and/or QT interval prolongation toxicity. Should treatment with any of these agents be required, consult with study chair and reference Section 5.5 for TKI dose modifications related to concomitant drugs.
Biologic/Vaccine, Drug, Other, Administration of antineoplastic agent, Drug therapy, Immunotherapy for cancer
Cancer, Chronic myelogenous leukemia, Leukemia
4-Methyl-N-(3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl)-3-((4-pyridin-3-ylpyrimidin-2-yl)amino)benzamide, Biological therapy for cancer, Cancer treatment, Chronic myeloid leukemia, Dasatinib, Hematopoietic system, Imatinib, Medical Oncology, Pembrolizumab [USAN:INN], dasatinib, imatinib, nilotinib, pembrolizumab
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