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A Phase 1 Trial of MK-4280 as Monotherapy and in Combination with Pembrolizumab with or without Chemotherapy or Lenvatinib (E7080/MK 7902) in Subjects with Advanced Solid Tumors

A Phase 1 Trial of MK-4280 as Monotherapy and in Combination with Pembrolizumab with or without Chemotherapy or Lenvatinib (E7080/MK 7902) in Subjects with Advanced Solid Tumors

Alex Adjei
All
18 years and over
Phase 1
This study is NOT accepting healthy volunteers
0000-100207-P01-RST
17-007205
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Inclusion Criteria:

  • Part A
    •Have a histologically or cytologically confirmed metastatic solid tumor for which there is no available therapy that may convey clinical benefit.
  • Part B – Have 1 of the following histologically or cytologically confirmed tumor types:
    • HNSCC that is considered incurable by local therapies. Subjects should have progressed after receiving platinum-containing systemic therapy. Systemic therapy given as part of multimodal treatment for locally advanced disease is allowed. The eligible primary tumor locations are oropharynx, oral cavity, hypopharynx, and larynx. Subjects may not have a primary tumor site of nasopharynx (any histology). Subjects enrolled in the PD-1-treatment-naïve HNSCC cohort may not have been treated with prior anti-PD-1/PD-L1 therapy.
    • Subjects enrolled in the PD-1-treatment-failure HNSCC cohort must be refractory to an FDA approved anti-PD-1/PD-L1 monoclonal antibody (mAb) as either monotherapy or in combination with other approved checkpoint inhibitors or other therapies according to their label, defined as (subjects must meet all of the following criteria):
      • Have received at least 2 doses of anti-PD-1/PD-L1 mAb.
      • Have progressive disease after anti-PD-1/PD-L1 mAb defined according to RECIST 1.1. The initial evidence of PD is to be confirmed by a second assessment, no less than 4 weeks from the date of the first documented PD, in the absence of rapid clinical progression.
      • Note:  this determination is made by investigator. If PD is confirmed, the initial date of PD documentation will be considered the date of disease progression.
      • Have documented PD within 24 weeks of the last dose of anti-PD-1/PD-L1 mAb. Patients who were re-treated with anti-PD-1/PD-L1 mAb and patients who were on maintenance with anti-PD-1/PD-L1 mAb will be allowed to enter the trial as long as there is documented PD within 24 weeks of the last treatment date (with anti-PD-1/PD-L1 mAb).
    • Adenocarcinoma of the stomach and/or gastric-esophageal junction (GEJ) that is considered inoperable and that has received, and progressed on, at least 1 prior chemotherapy regimen or HER2/neu-targeted approved therapy (if HER2/neu-positive). In both cases, subjects must not have been treated with prior anti-PD-1/PD-L1 therapy.
    • CRC for Arm 1 and Arm 2: CRC originating in either the colon or rectum that is locally advanced unresectable or metastatic (i.e., Stage IV) and that has received, and progressed on, all available standard-of-care therapies including fluoropyrimidine, oxaliplatin, and irinotecan but has not been treated with prior anti-PD-1/PD-L1 therapy.
    • CRC for Arm 3 and Arm 4: CRC originating in either the colon or rectum that is locally advanced unresectable or metastatic (i.e., Stage IV) and has been treated with ≤1 line of systemic therapy but has not been treated with prior anti-PD-1/PD-L1 therapy. Subjects eligible to receive EGFR-targeted therapy must have previously received this treatment in order to be eligible for the study.
      • Note – Subjects with known MSI high or MMR deficient gastric cancer or CRC (as determined by either PCR or IHC) are excluded from participating in this study. MSI high is defined as at least 2 allelic shifts occurring among the 5 analyzed microsatellite markers as detected by PCR. MMR deficient is defined as loss of expression of at least 1 of 4 proteins (MLH1, MSH2, MSH6, and/or PMS2) by IHC. If a subject’s MSI status is unknown, testing is not required to determine eligibility.
      • Note – Subjects who have withdrawn from standard treatment due to unacceptable toxicity warranting discontinuation of that treatment and precluding retreatment with the same agent before progression of disease will also be eligible.
      • Note – Subjects with CRC enrolled into Arm 3 or Arm 4 are not eligible to be re-enrolled in the study on Arm 1 or Arm 2 following discontinuation.
  • Have measureable disease by irRECIST 1.1 criteria.
  • Be ≥ 18 years of age on the day of signing informed consent.
  • Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
  • Demonstrate adequate organ function as defined in Table 3 (labs to be obtained within 7 days of initiation of treatment).
  • If female of childbearing potential, have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  • If female of childbearing potential, be willing to use an adequate method of contraception. Contraception, for the course of the study through 120 days after the last dose of study medication.
    • Note: Abstinence is acceptable if this is the usual lifestyle-preferred contraception for the subject.
  • Male subjects are eligible to participate if they agree to the following during the intervention period and for at least 95 days after the last dose of chemotherapy or 7 days after the last dose of lenvatinib, whichever occurs last:
    • Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent; OR
    • Must agree to use contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause) as detailed below:
    • Agree to use a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a WOCBP who is not currently pregnant.
    • Note: Men with a pregnant or breastfeeding partner must agree to remain abstinent from penile-vaginal intercourse or use a male condom during each episode of penile-vaginal penetration.
  • Voluntarily agree to participate by giving written informed consent/assent for the trial. The subject may also provide consent/assent for Future Biomedical Research. However, the subject may participate in the main trial without participating in Future Biomedical Research.
  • Submit an evaluable baseline tumor sample for PD-L1 analysis (either a newly obtained or archival tumor sample) as specified in the Procedure Manual.


Exclusion Criteria:

  • Has had chemotherapy, radiation, or biological cancer therapy within 4 weeks prior to the first dose of study therapy, or who has not recovered to CTCAE Grade 0 or 1 from the AEs due to cancer therapeutics administered more than 4 weeks earlier (this includes subjects who received previous immunomodulatory therapy with residual immune-related adverse events [irAEs]). Subjects receiving ongoing replacement hormone therapy for endocrine irAEs will not be excluded from participation in this study.
    • Note: Subjects with Grade 2 neuropathy are excluded from Arm 3 of Part B but may be eligible for all other arms of Part B.Is currently participating and receiving study therapy, or has participated in a study of an investigational agent and received study therapy, or used an investigational device within 4 weeks of the first dose of study treatment.
  • Has received previous treatment with another agent targeting the LAG-3 receptor.
  • Has received previous treatment with an immunomodulatory therapy (i.e., anti-PD-1/PD-L1 or CTLA-4 agent) and was discontinued from that therapy due to a Grade 3 or higher irAE.
  • Is expected to require any other form of antineoplastic therapy while on study.
  • Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy in excess of replacement doses, or on any other form of immunosuppressive medication. Subjects (i.e., with asthma) that require intermittent use of bronchodilators, inhaled steroids, or local steroid injections would not be excluded from the study.
  • Has a history of a previous, additional malignancy, unless potentially curative treatment has been completed, with no evidence of malignancy for 5 years.
    • Note: The time requirement for no evidence of disease for 5 years does not apply to the tumor for which a subject is enrolled in the study. The time requirement does not apply to subjects who underwent successful definitive resection of basal cell carcinoma of the skin, superficial bladder cancer or in situ cervical cancer, or other in situ cancers.
  • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are radiologically stable; i.e., without evidence of progression for at least 4 weeks by repeat imaging
    • Note that the repeat imaging should be performed during study screening, clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of trial treatment.
  • Has had a severe hypersensitivity reaction to treatment with another monoclonal antibody.
  • Has an active autoimmune disease or a documented history of autoimmune disease, except vitiligo or resolved childhood asthma/atopy. Replacement therapy (i.e., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
  • Has an active infection requiring therapy.
  • Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
  • Has had a prior stem cell or bone marrow transplant.
  • Has a known history of or screens positive for Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies), or an active chronic or acute Hepatitis B (i.e., hepatitis B surface antigen [HBsAg] reactive) or Hepatitis C infection (i.e., hepatitis C virus [HCV] RNA [qualitative] is detected).
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject’s participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • Is a regular user as determined by investigator judgment (including "recreational use") of any illicit drugs or has a recent history (within the last year) of substance abuse (including alcohol), at the time of signing informed consent.
  • Has symptomatic ascites or pleural effusion. A subject who is clinically stable following treatment for these conditions (including therapeutic thoraco- or paracentesis) is eligible.
  • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment.
  • Has clinically significant heart disease that affects normal activities.
  • Has had major surgery in the past 4 weeks.
  • Has received a live-virus vaccine within 30 days of planned treatment start. Seasonal flu vaccines that do not contain live virus are permitted.
  • Subjects being considered for enrollment into Arm 4 with CRC in Part B are also excluded if any of the following additional criteria apply:
    • Has plans to use, or is using, any herbal medications/supplements or any medications or foods that are strong inhibitors or inducers of cytochrome P450 3A 4/5 ≤1 week prior to the start of study treatment.
    • Has received previous treatment with irinotecan.
    • Has a known diagnosis of Gilbert’s Syndrome.
  • Prolongation of QTcF interval to > 480 ms.
  • NOTE: If the QTcF is prolonged to > 480 ms in the presence of a pacemaker, contact the Sponsor to determine eligibility.

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

 

 

Biologic/Vaccine, Drug, Administration of antineoplastic agent, Drug therapy
Cancer, Tumors and masses
Chemotherapy, Measurement, Medical Oncology, Solid tumor configuration, pembrolizumab
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Mayo Clinic — Rochester, MN

EA8134, International Penile Advanced Cancer Trial (International Rare Cancers Initiative Study) (InPACT)

International Penile Advanced Cancer Trial (International Rare Cancers Initiative Study)

Lance Pagliaro
Male
18 years and over
Phase 3
This study is NOT accepting healthy volunteers
0000-100210-P01-RST
17-006796
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Inclusion Criteria:

  • Male, aged 18 years or older.
  • Histologically-proven squamous cell carcinoma of the penis.
  • Stage:
    • any T, N1 (i.e., a palpable mobile unilateral inguinal lymph node OR a single radiologically-abnormal inguinal lymph node with no evidence of extra-nodal extension), M0 or;
    • any T, N2 (i.e., palpable mobile multiple or bilateral inguinal lymph nodes OR radiologically evident multiple or bilateral inguinal nodes with no evidence of extra-nodal extension), M0 or;
    • any T, N3 (i.e., fixed inguinal nodal mass or any pelvic lymphadenopathy), M0.
  • Measurable disease as determined by RECIST (version 1.1) criteria (InPACT-neoadjuvant only).
  • Performance Status ECOG 0, 1 or 2.
  • Patient is fit to receive the randomisation options for which he is being considered.
  • Haematology/biochemistry (as dictated by local hospital practice) should indicate fitness for randomisation options and parameters should be in line with considerations specified in the summary of product characteristics. Haematological parameters should not be supported by transfusion to enable entry into the trial. Liver function and renal function tests must form part of the pre-treatment assessment for patients who may be randomised to receive TIP chemotherapy; e.g., patients with impaired renal function may not be considered for arms B and C of InPACT-neoadjuvant but may be considered for arm A.
  • Patients being considered for InPACT-neoadjuvant must fulfil additional eligibility criteria.
  • Patients being considered for InPACT-pelvis must fulfil additional eligibility criteria.
  • Willing and able to comply with follow-up schedule.
  •  Written informed consent.


Exclusion Criteria:

  • Pure verrucous carcinoma of the penis.
  • Non-squamous malignancy of the penis.
  • Squamous carcinoma of the urethra.
  • Stage M1.
  • Previous chemotherapy or chemoradiotherapy outside of the InPACT trial.
  • Any absolute contraindication to chemotherapy if eligible for a chemotherapy/chemoradiotherapy randomisation.
  • Concurrent malignancy (other than SCC or Basal Cell Carcinoma of non-penile skin) that has required surgical or non-surgical treatment in the last 3 years.
  • Patients who are sexually active and unwilling to use effective contraception (if they are not already surgically sterile).
  • Radiological evidence of macroscopic pelvic lymph node disease on post-ILND cross-sectional imaging.
  • Patients with regionally advanced (N1-3, M0) penile cancer with disease burden that is considered unresectable by the credentialed InPACT surgeon* utilising standard inguinal, ilioinguinal lymphadenectomy resection and reconstructive techniques. For example, where procedures would require circumferential resection of the femoral or iliac vessels, or the requirement for hemipelvectomy.

* InPACT surgeon should consider reviewing the case with their National InPACT surgical lead where resectablity is unclear.

 

Drug, Procedure/Surgery, Radiation, Block dissection of inguinal lymph nodes, Pelvic lymphadenectomy
Cancer
Lymphadenectomy, Medical Oncology, Squamous cell carcinoma of penis
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Mayo Clinic — Rochester, MN

A Phase IB Trial of Neoadjuvant Multi-epitope HER2 Peptide Vaccine in Patients with HER2-expressing DCIS

Trial of Multi-epitope HER2 Peptide Vaccine in Patients with HER2-expressing DCIS

Amy Degnim
Female
18 years and over
Phase 1
This study is NOT accepting healthy volunteers
0000-100214-P01-RST
16-010561
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Registration

Inclusion Criteria:

  • Female age ≥ 18 years.
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
  • Patients must not have received any prior therapy for current DCIS.
    • Note:  Patients who received tamoxifen, raloxifene, aromatase inhibitor or another agent for prevention of breast cancer may be included as long as the patient has discontinued the treatment at least 2 months prior to baseline study biopsy if they chose to have this collected.
    • Note: Concurrent use of endocrine therapy during the vaccination/preoperative period is not allowed. However, standard adjuvant endocrine therapy with tamoxifen or aromatase inhibitor after completion of vaccination and surgery is allowed.
  • Any degree of HER2 expression as performed on the diagnostic clinical biopsy defined by immunohistochemistry +1, +2, or +3.
  • Histologically confirmed un-resected operable ductal carcinoma in situ with no evidence of lymph node involvement or distant metastasis.   Note: suspected microinvasion or definite microinvasion ( < 1 mm invasion) on core biopsy is allowed.
    • Note: suspected microinvasion or definite microinvasion (< 0.1 mm invasion) on core biopsy is allowed.
  • Patients will be asked to have an additional research biopsy prior to the first vaccination. This is not mandatory for participation.
  • Patients must have evidence of at least 1.0 cm of disease extent based on mammogram, or ultrasound, or MRI imaging.
  • Patients must have adequate organ and marrow function less than or equal to 28 days prior to Registration as defined below:
    • Absolute neutrophil count (ANC) ≥ 1500/mm^3;
    • Platelet count ≥ 75,000/mm^3;
    • Hemoglobin ≥ 9.0 g/dL;
    • Creatinine ≤ 2 x ULN;
    • SGOT (AST) ≤ 2 x ULN;
    • Albumin ≥ 3 g/dL.
  • Negative serum pregnancy test done ≤ 7 days prior to Registration, for women of childbearing potential only.
  • Willing to employ adequate contraception from the time of Registration through 6 months after the final vaccine cycle.
    • Note: Adequate contraception methods include birth control pills, barrier device, intrauterine device.
  • Capable of understanding the investigative nature, potential risks, and benefits of the study.
  • Capable of providing valid informed consent.
  • Willing to return to enrolling institution for all study visits (immunizations, blood draws, etc).
  • Willing to provide blood samples for correlative research purposes.
  • Willing to receive a tetanus vaccination if subject has not had one within the past year.

Registration


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 women;
    • Nursing women unwilling to stop breast feeding;
    • Women of child bearing potential who are unwilling to employ adequate contraception from the time of registration through 6 months after the final vaccine cycle.
  • 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 greater than or equal to 90 days prior to 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 less than or equal to 6 months prior to registration.
  • Receiving any other investigational agent.
  • Other active malignancy at time of registration or less than or equal to the last three years prior to 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 with a value below 55%.
  • 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.
  • History of ipsilateral radiation to the current affected breast with DCIS.

Eligibility last updated 1/21/22. Questions regarding updates should be directed to the study team contact.

 

Biologic/Vaccine, Drug, Administration of antineoplastic agent, Drug therapy, Oncolytic virus therapy
Breast cancer, Cancer, Ductal carcinoma in situ
Cancer treatment, Carcinoma in situ of female breast, HER2-positive carcinoma of breast, Medical Oncology, Virotherapy
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Mayo Clinic — Rochester, MN

ACCRU-ICRN-1701 A Phase I, Multi-Center, Open Label, Dose De-escalation and Expansion Study of Gemcitabine and Cisplatin with AG120 or Pemigatinib for Advanced Cholangiocarcinoma

A Phase I, Multi-Center, Open Label, Dose De-escalation and Expansion Study of Gemcitabine and Cisplatin with AG120 or Pemigatinib for Advanced Cholangiocarcinoma

Lionel Aurelien Kankeu Fonkoua
All
18 years and over
Phase 1
This study is NOT accepting healthy volunteers
0000-100221-P01-RST
20-000585
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Inclusion Criteria:

  • Histopathological diagnosis (fresh) or banked tumor biopsy sample collected within the last 3 years from the registration date consistent with nonresectable or metastatic cholangiocarcinoma and are not eligible for curative resection, transplantation, or ablative therapies.
  • Documented disease without any evidence of progression following at least 3 cycles of standard-of-care chemotherapy including gemcitabine and cisplatin as part of first-line systemic therapy.
    • Note: Only patients receiving standard-of-care chemotherapy including gemcitabine and cisplatin as first-line therapy for unresectable or metastatic cholangiocarcinoma will be permitted to enroll in this trial. Prior systemic adjuvant chemotherapy is allowed as long as there was no evidence of recurrence within 6 months of completing the adjuvant therapy.
  • Molecular testing result from Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory (using fresh tumor biopsy or most recent banked tumor tissue available) confirming that the tumor tissue has at least one of the following:
    • IDH1 gene mutation (R132C/L/G/H/S mutation);
    • FGFR2 gene alteration;
    • Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1;
    • Life expectancy ≥ 3 months;
    • At least one evaluable and measurable lesion by RECIST criteria prior to beginning chemotherapy with gemcitabine and cisplatin;
      • Note: Subjects who have received prior local therapy (including but not limited to embolization, chemoembolization, radiofrequency ablation, hepatic arterial infusion, or radiation therapy) are eligible provided measurable disease falls outside of the treatment.
  • Recovered from toxicities associated with prior anticancer therapy to baseline unless stabilized under medical management.
  • Absolute neutrophil count ≥ 1,500/mm^3 (obtained ≤ 21 days prior to registration).
  • Platelet count ≥ 100,000/mm^3 (obtained ≤ 21 days prior to registration).
  • Hemoglobin ≥ 8 g/dL (obtained ≤ 21 days prior to registration).
  • Serum total bilirubin ≤ 2.0 x upper limit of normal (ULN), unless considered due to Gilbert''s disease. If Gilbert''s disease or disease involving liver, serum total bilirubin ≤ 2.5 x ULN (obtained ≤ 21 days prior to registration).
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN or 5.0 x ULN in the presence of liver metastases (obtained ≤ 21 days prior to registration).
  • Serum creatinine < 1.5 x ULN OR creatinine clearance ≥ 50 mL/min based on the Cockcroft-Gault glomerular filtration rate (GFR) estimation (obtained ≤ 21 days prior to registration).
  • Serum phosphate ≤ institutional ULN and potassium within institutional normal range for Arm B only (obtained ≤ 21 days prior to registration).
    • Note: Supplemental potassium may be used to correct potassium prior to registration.
  • Negative serum pregnancy test done ≤ 7 days prior to registration for women of childbearing potential only.
    • Note: Females of reproductive potential are defined as sexually mature women who have not undergone a hysterectomy, bilateral oophorectomy, or tubal occlusion or who have not been naturally postmenopausal (i.e., who have not menstruated) for ≥ 24 consecutive months (i.e., have not had menses at any time in the preceding 24 consecutive months).
  • Women of reproductive potential and fertile men must agree to use 2 effective forms of contraception (including at least 1 barrier form) from the time of giving informed consent throughout the study and for 90 days (both females and males) following the last dose of study drug.
    • Note: Effective forms of contraception are defined as hormonal oral contraceptives, injectables, patches, intrauterine devices, intrauterine hormone-releasing systems, bilateral tubal ligation, condoms with spermicide, or male partner sterilization.
  • Able to understand and willing to sign the informed consent form.
    • Note: A legally authorized representative may consent on behalf of a subject who is otherwise unable to provide informed consent if acceptable to and approved by the site's Institutional Review Board (IRB)/Independent Ethics Committee (IEC).
  • Able to comply with scheduled visits, treatment plans, procedures, and laboratory tests, including serial peripheral blood sampling during the study.
  • Willing to provide blood samples for correlative research purposes. 


Exclusion Criteria:

  • Prior therapy with either an IDH inhibitor or selective FGFR inhibitor.
  • IDH inhibitors: ivosidenib, FT-2012, etc.
  • FGFR inhibitors: pemigatinib, BGJ-398, TAS-120, ARQ 087, or derazantinib, etc.
  • Progressive disease as best response on current standard-of-care chemotherapy including gemcitabine and cisplatin.
  • Known toxicity to standard-of-care chemotherapy including gemcitabine and cisplatin requiring cessation of this therapy.
  • Received radiotherapy to metastatic sites of disease ≤ 2 weeks prior to registration.
  • Underwent hepatic radiation, chemoembolization, or radiofrequency ablation ≤ 4 weeks prior to registration.
  • Known symptomatic brain metastases requiring steroids.
    • Note: Subjects with previously diagnosed brain metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to study entry, have discontinued corticosteroid treatment for these metastases for at least 4 weeks and have radiographically stable disease for at least 3 months prior to registration.
    • Note: Up to 10 mg per day of prednisone equivalent will be allowed.
  • Other active malignancy ≤ 5 years prior to registration. EXCEPTIONS:
    • Non- melanoma skin cancer unless stage 1a or carcinoma-in-situ of the cervix;
    • Breast cancer with ongoing hormone therapy being administered as adjuvant therapy;
      • Note: If there is a history or prior malignancy, they must not be receiving other specific treatment.
    • Major surgery ≤ 4 weeks prior to registration or have not recovered from post-surgery toxicities.
  • Any of the following because this study involves investigational agents whose genotoxic, mutagenic, and teratogenic effects on the developing fetus and newborn are unknown:
    • Pregnant women;
    • Nursing women;
    • Men or women of childbearing potential who are unwilling to employ adequate contraception.
  • Arm A: Use of strong CYP3A4 inducers or strong or moderate CYP3A4 inhibitors. In addition, sensitive CYP3A4 substrate medications with a narrow therapeutic window, unless they can be transferred to other medications ≤ 4 days or 5 half-lives (whichever is shorter) prior to registration
  • Arm B: Use of strong CYP3A4 inducers or inhibiitors or moderate CYP3A4 inducers.
    • Note: Study PI approval is needed if continued use of CYP3A4 inducers or inhibitors.
  • For Arm B only: Current evidence of clinically significant corneal (including but not limited to bullous/band keratopathy, corneal abrasion, inflammation/ulceration, and keratoconjunctivitis) or retinal disorder (including but not limited to central serous retinopathy, macular/retinal degeneration, diabetic retinopathy, retinal detachment) as confirmed by ophthalmologic examination.
  • Known history and/or current evidence of ectopic mineralization/ calcification, including but not limited to soft tissue, kidneys, intestine, myocardia, or lung, excepting calcified lymph nodes and asymptomatic arterial or cartilage/tendon calcification for Arm B only.
  • Known history of hypovitaminosis D requiring supraphysiologic doses to replenish the deficiency for Arm B only.
    • Note: Subjects receiving vitamin D food supplements are allowed.
  • Active infection requiring systemic anti-infective therapy or with an unexplained fever > 38.5 degrees Celsius (C) ≤ 7 days of registration.
    • Note: At the discretion of the investigator, subjects with tumor fever may be enrolled.
  • Any known hypersensitivity to any of the components of ivosidenib or pemigatinib.
  • Significant, active cardiac disease ≤ 6 months prior to registration, including:
    • New York Heart Association (NYHA) class III or IV congestive heart failure;
    • Myocardial infarction;
    • Unstable angina;
    • Stroke.
  • Have a heart-rate corrected QT interval (using Fridericia's formula) (QTcF) ≥ 450 msec or other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome).
    • Note: Bundle branch block and prolonged QTcF interval are permitted with approval of the medical monitor.
  • Taking medications that are known to prolong the QT interval, unless they can be transferred to other medications ≥ 5 half-lives prior to registration or unless the medications can be properly monitored during the study.
    • Note: If equivalent medication is not available, QTcF should be closely monitored.
  • Known active hepatitis B (hepatitis B virus [HBV]) or hepatitis C (hepatitis C virus [HCV]) infections, known positive human immunodeficiency virus (HIV) antibody results, or acquired immunodeficiency syndrome (AIDS) related illness.
    • Note: Subjects with a sustained viral response to HCV or immunity to prior HBV infection will be permitted. Subjects with chronic HBV that is adequately suppressed per institutional practice will be permitted.
    • Note: HBV, HCV, and/or HIV testing is not required prior to trial registration.
  • Any other acute or chronic medical or psychiatric condition, including recent (≤ 12 months of registration) or active suicidal ideation or behavior, or a laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.
  • Inability or unwillingness to swallow ivosidenib or pemigatinib or have significant gastrointestinal (GI) disorder(s) that could interfere with absorption, metabolism, or excretion.
  • Note: Gastroesophageal reflux disease under medical treatment is allowed (assuming no drug interaction potential).
  • Have been committed to an institution by virtue of an order issued either by the judicial or administrative authorities.
  • Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm.
Administration of antineoplastic agent, Chemotherapy, Drug therapy, Drug
Cancer, Cholangiocarcinoma
1,2-Diaminocyclohexaneplatinum II citrate, Cancer treatment, Chemotherapy, Cholangiocarcinoma of biliary tract, Digestive system, Gemcitabine [USAN:INN:BAN], Ivosidenib, Medical Oncology, Pemigatinib, Secondary malignant neoplasm of common bile duct, Targeted drug therapy, Tumor surgically unresectable, cisplatin, gemcitabine, ivosidenib
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LS1781, Phase 2 Trial of High Dose Intravenous Ascorbic Acid as an Adjunct to Salvage Chemotherapy in Relapsed / Refractory Lymphoma and Patients with Clonal Cytopenia of Undetermined Significance

A Study to Evaluate Ascorbic Acid and Chemotherapy to Treat Patients with Relapsed / Refractory Lymphoma and Patients with Clonal Cytopenia of Undetermined Significance

Thomas Witzig
All
18 years to 99 years old
Phase 2
This study is NOT accepting healthy volunteers
0000-100241-P01-RST
17-008096
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Inclusion Criteria:

Arms A, B and C Inclusion Criteria

  • Age ≥ 18 years.
  • Biopsy-proven relapsed or refractory lymphomas. Relapsed is defined as a relapse that occurred after having a response to the last therapy that lasted > 6 months. Refractory is no response or relapse within 6 months. Previous biopsies < 6 months prior to treatment on this protocol will be acceptable.
    • NOTE: Arms A/B – relapsed or refractory DLBCL within 24 months from the end of anthracycline-based therapy. No prior salvage therapy. Patients can have received radiation therapy as part of initial treatment but not specifically for relapse.
    • NOTE: Arm C patients include relapsed or refractory lymphoma patients of any type for which the recommended treatment includes one of the platinum-based regimens.  Of note, relapsed or refractory double-hit high grade lymphoma patients and relapsed or refractory Hodgkin lymphoma patients will be enrolled in Arm C. There is no limit on the number of prior therapies for Arm C patients. The patient must be eligible for a platinum-based regimen and must not have received the same regimen in the past without responding.
    • Measureable or assessable disease: Measureable disease is defined as measurable by CT (dedicated CT or the CT portion of a PET/CT) or MRI:
      • To be considered measureable, there must be at least one lesion that has a single diameter of ≥ 1.5 cm.
      • NOTE: Skin lesions can be used if the area is ≥ 1.5cm in at least one diameter and photographed with a ruler. Patients with assessable disease by PET are also eligible as long as the assessable disease is biopsy proven lymphoma.
    • Arms A/B – eligible for treatment with ifosfamide, carboplatin, and etoposide (± rituximab).
    • Arm C Eligible for treatment with one of the following standard, every 3 week, platinum-based salvage regimens (with or without monoclonal antibody as appropriate for the disease):
    • ifosfamide/carboplatin/etoposide (ICE) or (RICE);
    • cisplatin, cytosine arabinoside,  dexamethasone (DHAP) or RDHAP;
    • gemcitabine, dexamethasone, cisplatin (GDP) or RGDP;
    • gemcitabine and oxaliplatin (GemOx) or RGemOx;
    • Oxaliplatin, cytosine arabinoside, dexamethasone (OAD) or ROAD.
  • ECOG Performance Status (PS) 0, 1 or 2.
  • The following laboratory values obtained ≤ 14 days prior to registration (except creatinine which needs to be obtained ≤ 7 days prior to registration):
    • Hemoglobin ≥ 8.0 g/dL (may transfuse to meet this requirement);
    • Absolute neutrophil count (ANC) ≥ 1500/mm^3;
    • Platelet count ≥ 75000/mm^3;
    • Total bilirubin ≤ 2 x ULN (if > 2 x ULN direct bilirubin is required and should be ≤ 1.5 x ULN);
    • Alanine aminotransferase (ALT) and Aspartate transaminase (AST) ≤ 3 x ULN (≤ 5 x ULN for patients with liver involvement);
    • Creatinine ≤1.6 mg/dL. If over 1.6 then the Calculated creatinine clearance must be ≥ 55 ml/min using the Cockcroft-Gault formula below:
      • Creatinine clearance for males =    (140
        •age)(weight in kg)
      •                                                         ( 72)(serum creatinine in mg/dL);
      • Creatinine clearance for females = (140
        •age)(weight in kg)(0.85)
      •                                                         ( 72)(serum creatinine in mg/dL).
  • Negative pregnancy test done ≤ 7 days prior to 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.
  • HIV test done ≤ 14 days prior to registration.  If positive, the CD4 count must be > 400.
  • Provide written informed consent.
  • Willingness to have a central venous line (PICC or PORT)    
  • Willingness to provide mandatory blood specimens for correlative research.
  • Willingness to provide mandatory tissue specimens for correlative research.
  • Willingness to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study).
  • Willingness to follow the requirements of the intravenous ascorbic acid program schedule.

Arms A, B, and C 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.
  • Any therapy ≤ 2 weeks prior to registration.
    • EXCEPTIONS: Patients on ibrutinib or corticosteroids (any dose) may continue therapy up until the new regimen has started at investigator discretion. Corticosteroids can be tapered to lowest possible dose after start of treatment at investigator discretion. Patients can have monoclonal antibodies with steroids prior to registration.
    • EXCEPTION: Palliative radiation is allowed.
  • 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, pulmonary congestion or pulmonary edema, clinical dehydration, 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 lymphoma.
  • Other active malignancy than lymphoma.
    • NOTE: If there is a history of prior malignancy, they must not be receiving other specific treatment for their cancer that could interfere with this protocol therapy. Patients on hormonal therapy for treated breast or prostate cancer are permitted if they meet other eligibility criteria. Patients with non-melanotic skin cancer may enroll.
  • History of myocardial infarction ≤ 6 months, or current symptomatic congestive heart failure or LVEF < 40% or with > grade 2 diastolic dysfunction, with no symptoms or signs of heart failure.
  • Known G6PD (glucose-6-phosphate dehydrogenase) deficiency (below lower limit of normal).
  • Patients with active CNS lymphoma or active CSF involvement with malignant cells requiring CNS-specific therapy with IV or IT MTX.
    • NOTE: Patients with any prior CNS lymphoma (parenchymalor leptomeningeal) MUST be in CR in those compartments without any maintenance therapy required.
  • Patients with uncontrolled or symptomatic kidney stones.
  • Known paroxysmal nocturnal hemoglobinuria (PNH).

Arm D Inclusion Criteria

  • Patients who had a diagnosis of CCUS with one or more TET2 mutations or TET2 mutations with concurrent splicing genes mutations (SRSF2, U2AF1, SF3B1, and ZRSR2) or epigenetic regulator mutations (DNMT3A, EZH2, IDH1, IDH2). CCUS diagnosis being defined based on the absence of definitive morphologic evidence of hematologic neoplasms from bone marrow biopsy evaluation combined with evidence of pathogenic myeloid somatic mutation with a variant allele frequency (VAF) of at least 2% using our institution’s next generation sequencing (NGS) panel (OncoHeme, Mayo Clinic).
  • ECOG Performance Status (PS) 0, 1 or 2.
  • Patients must meet at least 1 of these 3 laboratory criteria to be enrolled and the values must be obtained ≤ 7 days prior to registration:
    • Hemoglobin ≤ 10g/dL;
    • Absolute neutrophil count (ANC) ≤ 1000/mm^3;
    • Platelet count ≤ 100,000/mm^3.
  • The following laboratory values must be obtained ≤ 7 days prior to registration:
    • Total bilirubin ≤ 2 x ULN (if > 2 x ULN direct bilirubin is required and should be ≤ 1.5 x ULN);
    • Alanine aminotransferase (ALT) and Aspartate transaminase (AST) ≤ 3 x ULN (≤ 5 x ULN for patients with liver involvement);
    • Creatinine ≤ 1.6 mg/dL. If > 1.6, then the Calculated creatinine clearance must be ≥ 55 ml/min using the Cockcroft-Gault formula below:
    • Creatinine clearance for males =     (140
      •age)(weight in kg)
    •                                                          ( 72)(serum creatinine in mg/dL);
    • Creatinine clearance for females =  (140
      •age)(weight in kg)(0.85)
    •                                                          ( 72)(serum creatinine in mg/dL).
  • Negative pregnancy test, 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.
  • Provide written informed consent.
  • Willingness to have a central venous line (PICC or PORT)   
  • Willingness to provide mandatory blood specimens for correlative research.
  • Willingness to return to enrolling institution (MCR) for follow-up (during the Active Monitoring Phase of the study).
  • Willingness to follow the requirements of the intravenous ascorbic acid program schedule.

Arm D Exclusion Criteria

  • Bona-fide hematological neoplasm.
  • 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.
  • 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, pulmonary congestion or pulmonary edema, clinical dehydration, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • History of myocardial infarction ≤ 6 months, or current symptomatic congestive heart failure or known LVEF < 40% or with > grade 2 diastolic dysfunction, with no symptoms or signs of heart failure.
  • Patients with uncontrolled or symptomatic kidney stones.
  • Known paroxysmal nocturnal hemoglobinuria (PNH).
  • Known G6PD (glucose-6-phosphate dehydrogenase) deficiency (below lower limit of normal)

Drug, Administration of antineoplastic agent, Drug therapy, Behavioral
Cancer, Diffuse large b-cell lymphoma, Hodgkin lymphoma, Lymphoma, Recurrent cancer
Cancer treatment, Chemotherapy, Hematopoietic system, Malignant lymphoma, Malignant lymphoma (clinical), Medical Oncology, ascorbic acid
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Mayo Clinic — Rochester, MN

NRG-BN005, A Phase II Randomized Trial of Proton Vs. Photon Therapy (IMRT) for Cognitive Preservation in Patients With IDH Mutant, Low to Intermediate Grade Gliomas

Proton Beam or Intensity-Modulated Radiation Therapy in Preserving Brain Function in Patients With IDH Mutant Grade II or III Glioma

Anita Mahajan
All
18 years and over
Phase 2
This study is NOT accepting healthy volunteers
0000-100243-P01-RST
17-009151
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Inclusion Criteria:

  • STEP 1 REGISTRATION
  • Tumor tissue must be available for submission for central pathology review
  • Documentation from the enrolling site confirming the presence of IDH mutation and 1p/19q status; the provided information must document assays performed in clinical laboratory improvement amendments (CLIA)-approved laboratories
  • Appropriate stage for study entry based on the following diagnostic workup:
    • History/physical examination within 60 days prior to registration
    • Imaging of the brain within 60 days prior to registration
  • Only English speaking patients are eligible to participate as the cognitive and quality of life assessments are available only in English
  • The patient or a legally authorized representative must provide study-specific informed consent prior to study entry
  • Karnofsky performance status of >= 70 within 60 days prior to registration
  • Absolute neutrophil count (ANC) >= 1,500 cells/mm^3
  • Platelets >= 100,000 cells/mm^3
  • Hemoglobin >= 10.0 g/dl (Note: The use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 10.0 g/dl is acceptable)
  • Bilirubin =< 1.5 upper limit of normal (ULN)
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x ULN
  • CD4 lymphocyte count is highly encouraged
  • Women of childbearing age must have a negative serum pregnancy test within 14 days prior to registration
  • Post-operative magnetic resonance (MR) imaging must be obtained for radiation therapy planning; enrolling sites are highly encouraged to obtain thin-slice volumetric fluid attenuated inversion recovery (FLAIR) and T1 post contrast sequences for planning purposes
  • STEP 2 REGISTRATION
  • The following baseline neurocognitive assessments must be completed and uploaded within 27 calendar days prior to step 2 registration: HVLT-R, TMT, and COWA
    • NOTE: Completed baseline neurocognitive assessments can be uploaded at the time of step 1 registration
  • The following baseline patient reported outcome assessments must be completed and uploaded within 27 calendar days prior to Step 2 registration: MDASI-BT, LASA QOL, WPAI
  • Financial clearance for proton therapy treatment within 30 days following step 1 registration
  • Centrally reviewed histologically proven diagnosis of supratentorial, Word Health Organization (WHO) grade II or III astrocytoma, oligodendroglioma or oligoastrocytoma; tissue must be submitted x calendar days after step 1 registration
  • Documentation must be uploaded within 15 business days and will be verified by the translational/pathology study co-chairs within 5 business days after receiving the upload; the documentation should demonstrate 1) evaluation of known IDH1 and IDH2 mutational hotspots (sequencing is encouraged) evaluation of chromosomes 1p and 19q copy number utilizing either fluorescence in situ hybridization (FISH) or other suitable assay


Exclusion Criteria:

  • Definitive clinical or radiologic evidence of metastatic disease; if applicable
  • Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years; (for example, carcinoma in situ of the breast, oral cavity or cervix are permissible)
  • Prior cranial radiotherapy or radiotherapy to the head and neck where potential field overlaps would exist
  • Prior chemotherapy or radiotherapy for any brain tumor
  • Histologic diagnosis of glioblastoma (WHO grade IV) or pilocytic astrocytoma (WHO grade I)
  • Definitive evidence of multifocal disease
  • Planned use of cytotoxic chemotherapy during radiation (only adjuvant temozolomide therapy will be used on this protocol)
  • Patients with infra-tentorial tumors are not eligible
  • Prior history of neurologic or psychiatric disease believed to impact cognitive function
  • The use of memantine during or following radiation is NOT allowed
  • Severe, active co-morbidity defined as follows:
    • Unstable angina or congestive heart failure requiring hospitalization within 6 months prior to enrollment
    • Transmural myocardial infarction within the last 6 months prior to step 2 registration; evidence of recent myocardial infarction or ischemia by the findings of S-T elevations of >= 2 mm using the analysis of an electrocardiogram (EKG) performed within 28 days prior to step 2 registration (Note: EKG to be performed only if clinical suspicion of cardiac issue)
    • New York Heart Association grade II or greater congestive heart failure requiring hospitalization within 12 months prior to step 2 registration
    • Serious and inadequately controlled arrhythmia at step 2 registration
    • Serious or non-healing wound, ulcer or bone fracture or history of abdominal fistula, intra-abdominal abscess requiring major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to step 2 registration, with the exception of the craniotomy for surgical resection
    • Acute bacterial or fungal infection requiring intravenous antibiotics at the time of step 2 registration
    • Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for coagulation parameters are not required for entry into this protocol
    • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of step 2 registration
    • Human immunodeficiency virus (HIV) positive with CD4 count < 200 cells/microliter; acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that HIV testing is not required for entry into this protocol
    • Any other severe immunocompromised condition
    • Active connective tissue disorders, such as lupus or scleroderma, that in the opinion of the treating physician may put the patient at high risk for radiation toxicity
    • End-stage renal disease (i.e., on dialysis or dialysis has been recommended)
    • Any other major medical illnesses or psychiatric treatments that in the investigator's opinion will prevent administration or completion of protocol therapy
  • Inability to undergo MRI with and without contrast (e.g. claustrophobia, non-MRI compatible implant or foreign body, gadolinium allergy or renal dysfunction preventing the patient from receiving gadolinium- institutional guidelines should be used to determine if patients are at risk for renal dysfunction); note that patients with severe claustrophobia are permitted on this study if they are willing and able to undergo MRI with adequate sedation or anesthesia

Drug, Radiation, Intensity modulated radiation therapy, Proton therapy
Brain tumor, Cancer, Glioma
IMRT, Low grade glioma of brain, Malignant glioma of brain, Medical Oncology, Nervous system, Proton therapy, Radiation therapy, Intensity-modulated radiation therapy
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MC1776 Neoadjuvant Therapy for Patients With High Risk Stage III Melanoma: A Pilot Clinical Trial (NeoACTIVATE)

Neoadjuvant Combination Targeted and Immunotherapy for Patients With High-Risk Stage III Melanoma

Matthew Block
All
18 years and over
Phase 2
This study is NOT accepting healthy volunteers
0000-100258-P01-RST
17-009383
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Inclusion Criteria
•Pre-Registration:

  • Age ≥18 years.
  • High-risk stage III melanoma, defined as (any of the following):
    • recurrent nodal metastasis; or
    • clinically detectable nodal metastasis; or
    • metastatic involvement of more than one nodal basin.
      • NOTE: For the purpose of pre-registration, high-risk stage III melanoma is defined based on clinical and imaging assessment (PET/CT, CT, or MRI). Histologic confirmation of nodal metastatic disease is not needed at the time of pre-registration, provided there is histologic confirmation of primary melanoma or a prior lymph node metastasis.
  • Willing to submit archival tissue from a lymph node biopsy or undergo a needle biopsy (with clip placement) for BRAF testing and for research purposes.
  • Willing to forego anticancer treatments or investigational agents during pre-registration period.
  • The following laboratory values obtained ≤28 days prior to pre-registration:
    • Only for patients receiving therapeutic anticoagulation: stable anticoagulant regimen and stable INR.

Exclusion Criteria
•Pre-Registration:

  • Prior systemic anti-cancer therapy for melanoma (e.g., chemotherapy, hormonal therapy, targeted therapy, immunotherapy including anti-PD-1, anti-PDL1 agents, or other biologic therapies), with the following exceptions: adjuvant treatment with interferon, IL-2, GM-CSF or vaccine therapies are allowed, if discontinued ≥28 days prior to pre-registration.
  • Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm.
  • For patients with concurrent diagnosis of primary melanoma with nodal involvement, major surgical procedure other than lymph node biopsy or wide local excision of primary melanoma ≤4 weeks prior to pre-registration, or anticipation of need for a major surgical procedure for reasons other than melanoma during the course of the study.
  • For patients with nodal recurrence, surgical procedure or anti-cancer therapy for this recurrence (other than lymph node biopsy) or anticipation of need for a major surgical procedure for reasons other than melanoma during the course of the study.
  • Prior radiotherapy for melanoma.
  • History non-nodal melanoma metastasis or CNS lesion(s) proven or clinically suspected to be metastasis.
  • Active malignancy (other than melanoma) or malignancy ≤3 years prior to pre-registration.
    • NOTE: Exceptions: Asymptomatic papillary thyroid cancer (not requiring treatment), Resected basal cell carcinoma (BCC), resected cutaneous squamous cell carcinoma (SCC), resected carcinoma in situ of the cervix, resected carcinoma in situ of the breast, in situ prostate cancer, non-muscle-invasive bladder cancer,Stage I uterine cancer, or other curatively treated malignancies from which the patient has been disease-free for at least 3 years prior to pre-registration.
  • Prior allogeneic stem cell or solid organ transplantation.
  • 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 CT scan.
  • History of autoimmune disease requiring systemic immunosuppressive or immune-modulatory therapy ≤5 years prior to pre-registration.
    NOTE: Exceptions are allowed for hypothyroidism on thyroid replacement therapy; or Type 1 diabetes on insulin regimen.
  • Active psoriasis requiring therapy (systemic or topical).
  • Known clinically significant liver disease, including alcoholism, cirrhosis, fatty liver, and other inherited liver disease as well as active viral disease.
  • Arms A and B only: History of or evidence of retinal pathology on ophthalmologic examination including but not limited to:
    • neurosensory retinal detachment;
    • central serous chorioretinopathy;
    • retinal vein occlusion (RVO);
    • neovascular macular degeneration.
  • Immunocompromised patients and patients known to be HIV positive and currently receiving antiretroviral therapy.
    • NOTE: Patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial.
  • Uncontrolled intercurrent illness including, but not limited to:
    • ongoing or active infection (including but not limited to tuberculosis);
    • clinically significant cardiac dysfunction including:
      • symptomatic congestive heart failure defined as New York Heart Association Class II or higher;
      • unstable angina pectoris or new-onset angina ≤3 months prior to pre-registration;
      • unstable cardiac arrhythmia;
      • myocardial infarction ≤3 months prior to pre-registration;
      • congenital long QT syndrome.
    • clinically significant stroke. reversible ischemic neurological defect, or transient ischemic attack ≤6 months prior to pre-registration;
    • any Grade 3 hemorrhage or bleeding event ≤4 weeks prior to pre-registration;
    • uncontrolled diabetes or symptomatic hyperglycemia;
    • psychiatric illness/social situations

that, in the judgement of the investigator, would
a) limit compliance with study requirements, or
b) make the patient inappropriate for entry into this study, or
c) interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.

  • Known hypersensitivity to biopharmaceutical agents produced in Chinese hamster ovary cells (ex: recombinant FSH).
  • Known hypersensitivity to any components of the atezolizumab (all arms), tiragolumab (Arm C only), cobimetinib (Arms A and B only), or vemurafenib (Arms A and B only) formulations.
  • History of severe allergic, anaphylactic or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins.

Inclusion Criteria
•Registration:

  • Histologic confirmation of Stage III melanoma, as defined by the American Joint Committee on Cancer, 8th revised edition.
  • Documentation of BRAFV600 mutation status in melanoma tumor tissue (archival or newly obtained) through use of a CLIA-approved clinical mutation test.
  • Surgically resectable disease, as determined by a melanoma surgical oncologist.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
  • Life expectancy ≥ 26 weeks.
  • The following laboratory values obtained ≤14 days prior to registration:
    • Absolute neutrophil count (ANC) ≥1500/mm3;
    • Platelet count ³100,000/mm3;
    • Hemoglobin ≥9.0 g/dL;
    • Direct bilirubin ≤institutional upper limit of normal (ULN);
    • Aspartate transaminase (AST) and alanine transaminase (ALT) £2 x ULN;
    • Alkaline phosphatase <2.5 x ULN;
    • Creatinine £1.5 x ULN or creatinine clearance (CrCl) ≥45 mL/min on the basis of measured CrCl from a 24-hour urine collection or Cockcroft-Gault glomerular filtration rate estimation:
      • CrCl=(140 - age) x (weight in kg)  (x 0.85 if female)
      •           72 x (serum creatinine in mg/dL).
  • Arms A and B only: LVEF ≥50% or institutional LLN ≤6 months prior to registration.
  • Arms A and B only: Average QTc≤450 ms on triplicate 12 lead ECG ≤28 days prior to registration.
  • Negative pregnancy test done ≤7 days prior to registration, for persons of childbearing potential only.
  • For persons of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use a contraceptive method with a failure rate of <1% per year during the treatment period and for 6 months after the last dose of study treatment.
  • For persons able to father a child: agreement to remain abstinent (refrain from heterosexual intercourse with a person of childbearing potential) or use contraceptive measures, and agreement to refrain from donating sperm during the treatment period and for 6 months after the last dose of study treatment.
  • Provide written informed consent.
  • Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study).
  • Willing to provide tissue, blood, and stool samples for correlative research purposes (see Sections 6.22, 14.1 and 17.1).
  • Arm C Only: Negative serology for acute Epstein-Barr virus (EBV) infection (negative EBV VCA IgM).

Exclusion Criteria
•Registration:

  • Received anticancer treatments or investigational agents during pre-registration period.
  • Clinically suspected non-nodal metastatic melanoma
  • Arm A only: For BRAF-mutant patients only: Anticipated use of any concomitant medication ≤7 days prior to registration that is known to cause QT prolongation (which may lead to torsade de pointes).
  • Arm A and B only: History of malabsorption or other clinically significant metabolic dysfunction that may interfere with absorption of oral study treatment or inability or unwillingness to swallow oral medication.
  • Signs or symptoms of infection or has received antibiotics ≤14 days prior to registration.
    • NOTE Patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study.
  • Any of the following because this study involves investigational agents 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.
  • Treatment with a live, attenuated vaccine ≤4 weeks prior to registration, or anticipation of need for such a vaccine during the course of the study
  • Treatment with systemic immunosuppressive medication (including, but not limited to, prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor (TNF)-a agents) ≤2 weeks prior to registration, or anticipation of need for systemic immunosuppressive medication during the course of the study
    • NOTE: Patients who have received acute, low-dose systemic steroids (£10 mg/day oral prednisone or equivalent) prior to registration or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible for the study.
    • NOTE: The use of inhaled corticosteroids for chronic obstructive pulmonary disease or asthma, mineralocorticoids (e.g., fludrocortisone), or low-dose corticosteroids for patients with orthostatic hypotension or adrenocortical insufficiency is allowed.
  • Requirement for concomitant therapy or food that is prohibited during the study, as described in Appendix III
  • Arms A and B only: Inability to abstain from alcohol during neoadjuvant phase.
  • Arm C only: Known Epstein-Barr virus (EBV) infection.
    NOTE: Patients with symptoms such as splenomegaly, fever, sore throat, non-malignant cervical lymphadenopathy, and/or tonsillar exudate, should undergo an EBV polymerase chain reaction (PCR) test to screen for acute infection or suspected chronic active infection. Patients with a positive EBV PCR test are excluded.
Drug, Administration of antineoplastic agent, Drug therapy
Cancer, Melanoma, Skin cancer
Atezolizumab, Biological therapy for cancer, Cancer treatment, Immunotherapy, Integumentary system, Malignant melanoma, Medical Oncology, Targeted drug therapy, atezolizumab, cobimetinib, vemurafenib
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A Phase 1 Multiple Dose Study to Evaluate the Safety and Tolerability of XmAb ®18087 in Subjects With Advanced Neuroendocrine and Gastrointestinal Stromal Tumors (DUET-1)

A Study of XmAb ®18087 in Subjects With NET and GIST

Timothy Hobday
All
18 years and over
Phase 1
This study is NOT accepting healthy volunteers
0000-100267-P01-RST
18-000904
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Inclusion Criteria:

  • Able to provide written informed consent.
  • Adult and adolescent (age ≥ 12 years) subjects.
  • Diagnosis of either:
    • Histologically or cytologically confirmed well-differentiated low or intermediate-grade (WHO Grade 1 or 2) NET of pancreatic, gastrointestinal, lung, or undetermined origin that is locally advanced or metastatic and has progressed within the past 12 months;
    • Histologically confirmed GIST that is locally advanced or metastatic.
      • Note: NET and GIST tumors must be unresectable.
  • NET subjects must have progressed on or been ineligible for treatment with somatostatin analogues (SSA) and at least one other targeted therapy. SSA therapy may continue if the subject has been on a stable dose for at least 3 months.
  • GIST subjects must have previously received all FDA-approved therapies (imatinib mesylate, sunitinib malate, and regorafenib) for which they are eligible.
  • Subjects must have disease measurable by RECIST 1.1 criteria using either CT or magnetic resonance imaging (MRI) scan.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Female subjects of childbearing potential must agree to use a highly effective method of birth control during and for 4 weeks after completion of study.
  • Women are considered to be of childbearing potential unless it is documented that they are:
    • over the age of 60; or
    • postmenopausal by history with no menses for 1 year and confirmed by FSH (using local reference ranges); or
    • have a history of hysterectomy and/or bilateral oophorectomy; or have a history of bilateral tubal ligation. Highly effective methods of birth control include hormonal birth control (oral, intravaginal, transdermal, implantable, or intrauterine), intrauterine devices (IUDs), vasectomy, or any double-barrier methods (combination of male condom and spermicide with cap, diaphragm, or sponge).
  • Able and willing to complete the entire study according to the study schedule.


Exclusion Criteria:

  • Diagnosis of high-grade (WHO Grade 3) or poorly differentiated NET; high-grade neuroendocrine carcinoma; adenocarcinoid or goblet cell carcinoid tumor; and large cell neuroendocrine carcinoma, small cell carcinoma, or mixed small and large cell carcinoma.
  • Subjects currently receiving anti-cancer therapies (other than SSAs, which may continue).
  • Subjects who have received anti-cancer therapies within 2 weeks of the start of study drug (including chemotherapy, radiation therapy, immunotherapy, etc.).
  • Failure to recover from Grade 3 or 4 toxicity from previous anti-cancer treatment.
  • Known central nervous system involvement by malignant disease.
  • Platelet count < 50 × 10^9 /L.
  • Absolute neutrophil count < 1.0 x 10^9/L.
  • Aspartate aminotransferase (AST) ≥ 3 × upper limit of normal (ULN), or if subject has known liver metastases, AST ≥ 7 × ULN.
  • Alanine aminotransferase (ALT) ≥ 3 × ULN, or if subject has known liver metastases, ALT ≥ 7 × ULN.
  • Estimated creatinine clearance < 50 mL/min calculated by the Cockroft Gault or Modification of Diet in Renal Disease formulas at screening.
  • Poorly controlled diabetes mellitus as evidenced by an HbA1c level ≥ 10%, or significant diabetes-related dietary or therapeutic regimen changes within 12 weeks of enrollment.
  • Active heart failure of New York Heart Association (NYHA) Functional Capacity Class III or IV.
  • Active autoimmune disease.
  • History or evidence of any other clinically unstable/uncontrolled disorder, condition, or disease (including, but not limited to, cardiopulmonary, renal, metabolic, hematologic or psychiatric) other than their primary malignancy that in the opinion of the Investigator would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.
  • Treatment for any serious bacterial, viral, parasitic, or systemic fungal infections within the 30 days prior to study entry.
  • Positive test for HIV or hepatitis C antibodies.
  • Positive test for HBsAg or HBcAb (a subject whose HBsAg is negative and HBcAb is positive may be enrolled if an HBV DNA test is negative and either the subject is treated with potent anti-viral therapy or is re-tested for HBsAg and HBV DNA every month).
  • Subject is pregnant or breastfeeding, or planning to become pregnant while enrolled in the study, up to the EOS visit.
  • Positive serum pregnancy test (i.e., urine human chorionic gonadotropin) at screening.

 

 

Biologic/Vaccine, Administration of antineoplastic agent, Drug therapy
Cancer, Gastrointestinal stromal tumors, Neuroendocrine carcinoma, Recurrent cancer
Cancer treatment, Gastrointestinal stromal tumor, Malignant neuroendocrine tumor, Medical Oncology
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An Open-Label, Dose Escalation and Dose Expansion Trial Evaluating the Safety, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of Orally Administered CA-4948 in Patients with Relapsed or Refractory Primary Central Nervous System Lymphoma (CA-4948 in NHL)

A Study of CA-4948 in Patients With Relapsed or Refractory Primary Central Nervous System Lymphoma

Grzegorz Nowakowski
All
18 years and over
Phase 1/2
This study is NOT accepting healthy volunteers
0000-100278-P01-RST
17-009647
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Inclusion Criteria:


1. Males and females greater than or equal to 18 years of age

2. Life expectancy of at least 3 months

3. Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 1

4. For Part A1: Diagnosis of histopathologically confirmed B-cell hematological
malignancy (as per the World Health Organization [WHO] 2016 classification; Swedow
2016); eligible subtypes include follicular lymphoma, MZL, DLBCL, mantle cell
lymphoma, and WM/LPL without the urgent need for treatment hyperviscosity.

For Part A2: Diagnosis of histopathologically confirmed B-cell NHL, as per the WHO 2016
classification (Swerdlow et al. 2016). Eligible NHL subtypes include follicular lymphoma,
MZL, mantle cell lymphoma, DLBCL(including extranodal lymphomas of leg-, testicular-, or
NOS type), CLL/SLL, primary or secondary CNS lymphoma and WM/LPL.

For Part B: Diagnosis of histopathologically confirmed B-cell NHLs, including applicable
confirmation as per the WHO 2016 classification (Swerdlow et al. 2016):

- Cohort 1: Marginal zone lymphoma

- Cohort 2: ABC-DLBCL, or extranodal subtypes: Leg-, testicular-, or NOS-type. The
population will be enriched for MYD88 L265P mutations. As this occurs more frequently
in the ABC-DLBCL(activated B-cell (Hans et al. 2004) subtype, all patients with this
subtype qualify for enrollment. If the MYD88 mutation status is unknown at baseline,
the lymphoma will be tested for MYD88 mutations.

- Cohort 3: Primary CNS Lymphoma (PCNSL) only. If the MYD88 mutation status is unknown
at baseline, the lymphoma will be tested for MYD88 mutations.

- Cohort 4: Patients receiving ibrutinib monotherapy who have developed adaptive,
secondary resistance. Indications include:

- MCL, MZL, CLL/SLL, or WM/LPL

- Indications for which ibrutinib is NCCN-listed (e.g., PCNSL)

- Patients with NHL and known myddosome mutations

- Patients may be candidates for maintaining ibrutinib while emavusertib will be
added for resistance reversal. A brief gap of ibrutinib therapy of <3 weeks is
acceptable.


Exclusion Criteria:


1. Patient with active central nervous system (CNS) involvement other than PCNSL at study
entry are ineligible.

2. Radiotherapy delivered to non-target lesions involving >25% of bone marrow within one
week prior to starting study treatment or delivered to target lesions that will be
followed on the study (NOTE: prior sites of radiation will be recorded)

3. Any prior anti-cancer treatment such as chemotherapy, immunomodulatory drug therapy,
etc., received within 14 days prior to start of study treatment (with the exception of
ibrutinib for Parts A2 and B, which may be continued as part of this study without
interruption)

4. Current or planned glucocorticoid therapy, with the following exceptions:

1. Doses ≤ 10 mg/day prednisolone or equivalent is allowed, provided that the
steroid dose has been stable or tapering for at least 14 days prior to the first
dose of study treatment

2. Inhaled, intranasal, intraarticular and topical steroids are permitted

5. Use of any investigational agent within 21 days or 5 half-lives, whichever is shorter,
prior to start of study treatment

6. Presence of an acute or chronic toxicity resulting from prior anti-cancer therapy,
with the exception of alopecia, that has not resolved to Grade ≤ 1 within 7 days prior
to start of study treatment unless approved by the Medical Monitor

7. Known allergy or hypersensitivity to any component of the formulation of emavusertib
(or ibrutinib for entry into Parts A2 or B) used in this study

8. B-cell NHL of the following subtypes:

1. Burkitt lymphoma

2. Lymphoblastic lymphoma or leukemia

3. Post-transplantation lymphoproliferative disorder

4. Known primary mediastinal, ocular, or epidural, DLBCL

5. WM patients requiring urgent treatment due to hyperviscosity

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

Eligibility last updated 10/12/22. Questions regarding updates should be directed to the study team contact.

Drug, Administration of antineoplastic agent, Drug therapy
Cancer, Lymphoma, Non-Hodgkin's lymphoma, Recurrent cancer
Cancer treatment, Hematopoietic system, Medical Oncology, Non-Hodgkin's lymphoma (clinical)
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BS001 - Aggressive Smoldering Curative Approach Evaluating Novel Therapies (ASCENT): A Phase 2 Trial of Induction, Consolidation, and Maintenance in Subjects With High Risk Smoldering Multiple Myeloma (SMM) (ASCENT)

Aggressive Smoldering Curative Approach Evaluating Novel Therapies and Transplant

Shaji Kumar
All
18 years to 80 years old
Phase 2
This study is NOT accepting healthy volunteers
0000-100284-P01-RST
17-010034
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Inclusion Criteria:

  • Age ≥ 18 years and ≤ 80 years old.
  • High risk smoldering myeloma, which is untreated, as defined by presence of any two of the following:
    • Serum M spike > 2 gm/dL; OR
    • An involved to uninvolved FLC ratio > 20; OR
    • Bone marrow PC% > 20%.
  • Total score of 9 or above using the following scoring system:
    • FLC Ratio >10-25
      • Score:  2
    • FLC Ratio >25-40
      • Score:  3
    • FLC Ratio > 40
      • Score:  5
  • Serum M protein (g/dL)
    • > 1.5-3
      • Score: 3
    • > 3
      • Score:  4
  • BMPC%
    • >15-20
      • Score: 2
    • > 20-30
      • Score: 3
    • > 30-40
      • Score:  5
    • > 40
      • Score:  6
  • FiSH abnormality (t(4,14), t(14,16), 1q gain, or del13q
    • Score:  2
  • The following laboratory values obtained ≤ 14 days prior to registration:
    • Calculated creatinine clearance (using Cockcroft-Gault equation below)* ≥ 30 mL/min;
    • Absolute neutrophil count (ANC) ≥ 1000/mm³ (without the use of growth factors);
    • Platelet count  ≥ 75000/mm ³;
    • Hemoglobin ≥ 8.0 g/dL;
    • Total bilirubin ≤ 1.5 x ULN;
    • ALT and AST ≤ 3 x ULN;
  • *Cockcroft-Gault Equation:
    • Creatinine clearance for males = (140
      •age)(actual body weight in kg)/ (72)(serum creatinine in mg/dL);
    • Creatinine clearance for females = (140
      •age)(actual body weight in kg)(0.85)/(72)(serum creatinine in mg/dL).
  • LVEF ≥ 40%.
  • ECOG performance status (PS) 0 or 1.
  • Previously untreated.
  • Provide informed written consent.
  • Negative pregnancy test done ≤ 14 days prior to C1D1, for women of childbearing potential only.
  • All study participants must be registered into the mandatory Revlimid REMSR program and be willing and able to comply with the requirements of the REMSR program.
  • Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMSR program.
  • Willing to follow strict birth control measures as outlined in the protocol.  Female subjects: If they are of childbearing potential, agree to one of the following:
    • Practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form through 90 days after the last dose of trial drug; AND
    • Must also adhere to the guidelines of any treatmentspecific pregnancy prevention program, if applicable; OR
    • Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception).
  • Male subjects: even if surgically sterilized (i.e., status post-vasectomy), must agree to one of the following:
    • Agree to practice effective barrier contraception during the entire trial treatment period and through 90 days after the last dose of trial drug; OR
    • Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable; OR
    • Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception).
  • Willing to return to enrolling institution for follow-up during the Active Treatment Phase of the trial.
  • Male subjects must agree not to donate sperm for at least 90 days after the last dose of study treatment.
  • Willing to provide samples for planned research.
  • Life expectancy > 6 months.
  • Able to take aspirin (325 mg) daily as prophylactic anticoagulation. Subjects intolerant to aspirin may use warfarin, novel oral anticoagulants, or low dose molecular weight heparin.


Exclusion Criteria:

  • MGUS, standard risk smoldering myeloma, active myeloma by current IMWG definition, light chain amyloidosis with organ involvement or patients with extramedullary disease.
  • Diagnosed or treated for another malignancy ≤ 2 years before trial enrollment or previously diagnosed with another malignancy and have any evidence of residual disease.
    • NOTE: Subjects with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
  • If any of the following exist at screening, subject will not be eligible for trial because this trial involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:
    • Pregnant women;
    • Nursing women;
    • Men or women of childbearing potential who are unwilling to employ adequate contraception (per protocol).
  • Other co-morbidity which would interfere with subject's ability to participate in trial; e.g., uncontrolled infection, uncompensated heart or lung disease.
  • Other concurrent chemotherapy, or any ancillary therapy considered investigational.
    • NOTE: Bisphosphonates are considered to be supportive care rather than therapy, and are thus allowed while on protocol treatment.
  • Peripheral neuropathy ≥ Grade 3 on clinical examination or grade 2 with pain within 30 days prior to C1D1.
  • Major surgery ≤ 14 days prior to C1D1.
  • Evidence of current uncontrolled cardiovascular conditions, including hypertension, cardiac arrhythmias, congestive heart failure, unstable angina, or myocardial infarction within the past 6 months.
    • Note: Prior to trial entry, any ECG abnormality at screening must be documented by the investigator as not medically relevant.
  • NYHA II, III, IV heart failure.
  • Known human immunodeficiency virus (HIV) positive.
  • Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg]). Subjects with resolved infection (i.e., subjects who are HBsAg negative but positive for antibodies to hepatitis B core antigen [anti-HBc] and/or antibodies to hepatitis B surface antigen [anti-HBs]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) DNA levels. Those who are PCR positive will be excluded.
    • EXCEPTION: subjects with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR.
  • Known or suspected active hepatitis C infection.
  • Any medical or psychiatric illness that could, in the investigator’s opinion, potentially interfere with the completion of treatment according to this protocol.
  • Prior radiation therapy for bony lesions or plasmacytomas
  • Known allergies, hypersensitivity, or intolerance to corticosteroids, monoclonal antibodies or human proteins, or their excipients (refer to respective package inserts or Investigator's Brochure), or known sensitivity to mammalian-derived products. Known allergies, hypersensitivity, or intolerance to trial drugs.
  • Inability to comply with protocol/procedures.

Drug, Administration of antineoplastic agent, Chemotherapy, Drug therapy, Immunotherapy for cancer
Cancer, Multiple myeloma, Plasma cell disorders
Biological therapy for cancer, Bone marrow transplant, Cancer treatment, Carfilzomib, Chemotherapy, Daratumumab [USAN:INN], Dexamethasone, Hematopoietic system, Immune system, Lenalidomide, Medical Oncology, Smoldering myeloma, Targeted drug therapy, carfilzomib, daratumumab, dexamethasone, lenalidomide
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A Phase I Trial of Sonidegib and Pembrolizumab in Advanced Solid Tumors

A Study of Sonidegib and Pembrolizumab in Advanced Solid Tumors

Mojun Zhu
All
18 years and over
Phase 1
This study is NOT accepting healthy volunteers
0000-100292-P01-RST
18-007218
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Inclusion Criteria:

  • Age ≥ 18 years.
  • Measurable disease by RECIST criteria as defined in Section 11.0.
  • ECOG Performance Status (PS) of 0 or 1.
  • The following laboratory values obtained ≤ 28 days prior to registration:
    • Hemoglobin ≥ 9.0 g/dL;
    • Absolute neutrophil count (ANC) ≥ 1000/mm^3;
    • Platelet count ≥ 100,000/mm^3;
    • Total bilirubin ≤ 1.5 x ULN OR direct bilirubin ≤ ULN;
    • Alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤ 2.5 x ULN (≤ 5 x ULN for patients with liver involvement);
    • Creatine Phosphokinase (CK) ≤ 2.5 x ULN.
    • Serum creatinine ≤ 1.5 x ULN or Calculated creatinine clearance ≥ 50 ml/min using the Cockcroft-Gault formula below:
    • Creatinine clearance for males = (140
      •age)(weight in kg) (72)(serum creatinine in mg/dL).
    • Creatinine clearance for females = (140
      •age)(weight in kg)(0.85)      (72)(serum creatinine in                mg/dL).
  • Negative serum pregnancy test done ≤ 7 days prior to registration, for persons of childbearing potential only.
  • Patients of childbearing potential agree to use two forms of medically approved contraception while taking the study drug and for 20 months following the last dose of study drug. Patients with partners of childbearing potential agree to use condoms, even after vasectomy, to avoid potential drug exposure to partner during study drug and for 8 months following the last dose of study drug.
  • Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study)
  • Willing to provide blood samples for correlative research purposes.
  • Must be able to swallow capsules and have no significant impairment in gastrointestinal absorption.
  • Willing and able to provide informed consent.

Inclusion Criteria-  Part A (Dose Escalation):

  • Patients with NSCLC.
  • Pathologically confirmed metastatic non-small cell lung cancer (NSCLC).
  • Tumor expression of PD-L1 (tumor propensity score ≥ 1%) as determined using an FDA-approved test.
  • Disease progression on prior platinum-containing chemotherapy.
    • NOTE: Previous treatment using PD-1/PD-L1 checkpoint inhibitors is allowed.
  • Patients with EGFR, ALK, or BRAF genomic abnormalities must have also received and progressed on prior FDA-approved targeted therapies.
  • Melanoma.
  • Unresectable or metastatic melanoma.
    • NOTE: Previous treatment using PD-1/PD-L1 checkpoint inhibitors is allowed.
  • Head and neck squamous cell cancer (HNSCC):
    • Recurrent or metastatic HNSCC after progression on prior platinumcontaining chemotherapy;
    • NOTE: Previous treatment using PD-1/PD-L1 checkpoint inhibitors is allowed.
    • Urothelial Carcinoma (locally advanced or metastatic);
    • Newly diagnosed Cisplatin ineligible patients; OR
    • Progression during or within 12 months of treatment with platinumcontaining agent,
  • Microsatellite Instability–High (MSI-H) Cancer
  • Unresectable or metastatic solid tumors that progressed on prior treatment and are MSI-H or mismatch repair deficient
  • No satisfactory alternative treatment options available. For colorectal cancer, must have progressed following treatment with fluoropyramidine, oxaliplatin, and irinotecan.
  • Gastric or Gastroesophageal Junction Adenocarcinoma.
  • Locally advanced or metastatic tumors that express PD-L1 as evidenced by a combined positive score (≥ 1) using the PD-L1 IHC 223C pharmDx test (Dako).
  • Disease progression on 2 or more prior systemic therapies.

Inclusion Criteria
•Part B (Dose Expansion):

  • Cohort A- Refractory Metastatic or Inoperable Pancreatic Adenocarcinoma.
  • Pathologically confirmed metastatic or inoperable pancreatic adenocarcinoma.
  • Received at least (≥)1 prior line of systemic chemotherapy for advanced or metastatic disease.
  • Cohort B- Refractory NSCLC
  • Pathologically confirmed metastatic non-small cell lung cancer (NSCLC)
  • Tumor expression of PD-L1 (tumor propensity score ≥ 1%) as determined using an FDA-approved test
  • Disease progression on ≥ 2 prior lines of systemic therapy, including prior platinum-containing chemotherapy
    • NOTE: Previous treatment using PD-1/PD-L1 checkpoint inhibitors is allowed.
  • Patients with EGFR, ALK, or BRAF genomic abnormalities must have also received and progressed on prior FDA-approved targeted therapies.

Exclusion Criteria
•Registration:

  • 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 and with partners of childbearing potential who are unwilling to employ adequate contraception.
  • CTCAE ≥ Grade 3 treatment-emergent adverse event (TEAE) to prior checkpoint inhibitor, TEAE requiring systemic corticosteroids, or permanent treatment discontinuation due to toxicity.
  • Neuromuscular disorders (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis and spinal muscular atrophy), or a history of rhabdomyolysis.
  • Concomitant treatment with drugs that are recognized to cause rhabdomyolysis, including statins.
    • NOTE: Patients taking such medications need to be discontinued at least 2 weeks or five half-lives, whichever is longer, prior to starting sonidegib treatment. If an agent to control lipids is required, pravastatin may be given with caution.
  • Receiving strong inhibitors or inducers of CYP3A4/5, moderate inducers of CYP3A4, and/or grapefruit/grapefruit juice or starfruit products that cannot be discontinued before starting treatment with sonidegib.
    • NOTE: Medications that are strong CYP3A4/5 inhibitors or inducers, moderate inducers of CYP3A4, and grapefruit/ grapefruit juice/starfruit products should be discontinued at least 14 days or 5 half-lives, whichever is longer, prior to starting treatment with sonidegib.
  • Active autoimmune diseases that have required systemic treatment modifications within the past 3 months or that require chronic systemic steroids or immunosuppressive agents.
  • Requirement for systemic corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications ≤ 14 days prior to registration.
  • Life expectancy < 3 months.
  • Central nervous system metastases that are untreated, symptomatic, or require steroids.
    • NOTE: Patients with history of stable treated brain metastases are eligible. Stable treated metastases are defined as follows:
    • No evidence of progression for ≥8 weeks on brain imaging (either MRI or CT scan);
    • No corticosteroid use for brain metastases for ≥ 2 weeks before randomization;
    • ≥ 8 weeks from completion of definitive treatment for brain metastases.
  • Any of the following prior therapies:
    • Major Surgery ≤ 4 weeks prior to registration;
    • Received any experimental drugs or anti-neoplastic therapy ≤ 4 weeks prior to receiving the first dose of study treatment;
    • Received a live vaccine ≤ 30 days prior to registration.
  • 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.
  • Ongoing AE due to prior treatment not recovered to ≤ Grade 1 per CTCAE or baseline unless clinically nonsignificant and/or stable with supportive therapy

 

Drug, Other, Administration of antineoplastic agent, Drug therapy, Immunotherapy for cancer
Cancer, Colon cancer, Head and neck cancer, Lung cancer, Melanoma, Non-small cell lung cancer, Pancreatic cancer, Skin cancer, Stomach cancer, Metastatic melanoma, Stage 4 melanoma
Adenocarcinoma of pancreas, Adenocarcinoma of stomach, Biological therapy for cancer, Cancer treatment, Digestive system, Erismodegib, Integumentary system, Malignant melanoma, Malignant tumor of head and neck, Medical Oncology, Metastatic malignant melanoma, Metastatic non-small cell lung cancer, Microsatellite instability-high solid malignant tumor, Non-small cell lung cancer, Pembrolizumab [USAN:INN], Primary adenocarcinoma of esophagogastric junction, Respiratory system, Secondary malignant neoplasm of pancreas, Solid tumor configuration, pembrolizumab, sonidegib, Sonidegib
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Phase III Trial of Observation Versus Irradiation for a Gross Totally Resected Grade II Meningioma

Observation or Radiation Therapy in Treating Patients With Newly Diagnosed Grade II Meningioma That Has Been Completely Removed by Surgery

Kenneth Merrell
All
18 years and over
Phase 3
This study is NOT accepting healthy volunteers
0000-100295-P01-RST
17-009813
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Inclusion Criteria:

  • PRIOR TO STEP 1 REGISTRATION:
  • The patient must have a newly diagnosed unifocal intracranial meningioma, gross totally resected, and histologically confirmed as WHO grade II based upon pathology findings at the enrolling institution; WHO grade will be assigned according to WHO 2016 criteria
  • Gross total resection (GTR) will be interpreted as modified Simpson grade 1-3 without gross residual dural-based or extradural tumor; GTR must be confirmed both by modified Simpson grade and by post-operative magnetic resonance imaging (MRI) findings
  • Step 1 registration must occur within 180 days of the initial surgery; within this 180 day interval, a second surgery is permitted in order to achieve GTR, but even with a second surgery, step 1 registration must occur within 180 days of the initial resection
  • For step 1 registration the operating neurosurgeon must provide the modified Simpson grade
  • GTR must be confirmed on post-operative imaging following the most recent surgery; submission of both pre-operative and post-operative MRIs is required for patients; if a second surgery is performed, submission of post-operative MRI is required and pre-operative MRI is required only if obtained; all sequences obtained in the pre- and post-operative MR imaging are to be submitted to National Radiology Group (NRG) Oncology for study registration; imaging subsequent to enrollment must include pre and post gadolinium contrast-enhanced three-dimensional spoiled gradient (SPGR), magnetization-prepared rapid gradient echo (MP-RAGE), or turbo field echo (TFE) MRI scan and an axial T2 fluid attenuated inversion recovery (FLAIR) sequence; to yield acceptable image quality, the gadolinium contrast-enhanced three-dimensional SPGR, MP-RAGE, or TFE axial MRI scan should use the smallest possible axial slice thickness not exceeding 1.5 mm; the post-operative MRI must be completed within sufficient time to permit step 1 registration within 180 days of the initial resection; these same conditions apply in the setting of a second surgical procedure, although if a second surgery is completed, step 1 registration must still occur with 180 days of initial surgery; computed tomography (CT) imaging is not required, but may be obtained if desired clinically, for instance to assess calcifications or hyperostosis
  • The patient or a legally authorized representative must provide study-specific informed consent prior to study entry
  • If the patient is a primary English speaker, the patient must participate in the NCF and patient reported outcomes part of the study; if the patient is a primary French or Spanish speaker, the patient must participate in the patient reported outcomes part of the study
  • NOTE: Central pathology review must occur between steps 1 and 2 of registration; once appropriate pathology specimens are received, central pathology review will occur within 15 days, and must confirm WHO grade II meningioma before the patient can proceed to step 2 registration and randomization
  • PRIOR TO STEP 2 REGISTRATION:
  • Histologically confirmed diagnosis of WHO grade II meningioma confirmed by central pathology review prior to step 2 registration
  • History/physical examination, including neurologic examination within 60 days prior to step 2 registration
  • Post-operative Zubrod performance status 0-1 within 60 days prior to step 2 registration
  • If the patient is a woman is of childbearing potential, a serum pregnancy test, obtained within 14 days prior to step 2 registration, must be negative, and, if randomized to receive radiation therapy, the woman must agree to use contraception


Exclusion Criteria:

  • Optic nerve sheath meningioma, spinal or other extracranial meningioma, multiple meningiomas, hemangiopericytoma
  • Definitive evidence of metastatic meningioma
  • Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years (carcinoma in situ of the breast, oral cavity, cervix, melanoma in situ, or other non-invasive malignancies are permissible)
  • Previous radiotherapy to the scalp, cranium, brain, or skull base and radiation-induced meningiomas
  • Major medical illnesses or psychiatric impairments, which in the investigators opinion, will prevent administration or completion of the protocol therapy and/or preclude informed consent; these include, but are not restricted to:
    • Unstable angina and/or congestive heart failure requiring hospitalization at the time of step 2 registration
    • Transmural myocardial infarction within the last 6 months prior to step 2 registration
    • Acute bacterial or fungal infection requiring intravenous antibiotics at the time of step 2 registration
    • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of step 2 registration
    • Type II neurofibromatosis (NF2)
    • Ailments entailing substantial increases in sensitivity and side effect risk from radiation therapy (ataxia telangiectasia, Nijmegen breakage syndrome, and human immunodeficiency virus (HIV) with CD4 count < 200 cells/microliter); HIV testing is not required for eligibility for this protocol, and known HIV positive patients are eligible, provided they are under treatment with highly active antiretroviral therapy (HAART) and have a CD4 count >= 200 cells/microliter within 30 days prior to step 2 registration
    • Inability to undergo MRI with and without contrast (e.g. claustrophobia, non-MRI compatible implant or foreign body, etc) or receive gadolinium; note that patients with severe claustrophobia are permitted on this study if they are willing and able to undergo MRI with adequate sedation or anesthesia
  • Pregnancy and/or nursing females

Radiation, Active surveillance, Radiation therapy procedure or service, Radiation oncology AND/OR radiotherapy
Brain tumor, Cancer, Meningioma
Cancer treatment, Central nervous system, Intracranial meningioma, Medical Oncology, Nervous system, Radiation therapy
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EA4151, A Randomized Phase III Trial of Consolidation With Autologous Hematopoietic Cell Transplantation Followed by Maintenance Rituximab vs. Maintenance Rituximab Alone for Patients With Mantle Cell Lymphoma in Minimal Residual Disease-Negative First Complete Remission

Rituximab With or Without Stem Cell Transplant in Treating Patients With Minimal Residual Disease-Negative Mantle Cell Lymphoma in First Complete Remission

Patrick Johnston
All
18 years to 70 years old
Phase 3
This study is NOT accepting healthy volunteers
0000-100301-P01-RST
17-010523
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Inclusion Criteria:

INCLUSION CRITERIA FOR SCREENING (STEP 0
•PREREGISTRATION)

  • Age ≥ 18 and ≤ 70 years.
  • Patients must have histologically confirmed mantle cell lymphoma, with cyclin D1 by immunohistochemical stains and/or t(11;14) by cytogenetics or FISH. The proliferation rate, using Ki-67 or MIB-1, should also be determined, but is not required until Step 1 registration. Patients may register to Step 0 without a documented Ki-67 index.
  • In the opinion of the enrolling physician, patients must be felt to be a candidate for autologous stem cell transplantation.
  • Patient may be about to begin, be receiving, or have completed induction therapy within 120 days prior to preregistration to Step 0.  No more than 300 days may have passed between the first day of induction therapy and preregistration to Step 0.
  • For patients who have completed induction therapy and have been restaged, restaging evaluation must show status of partial (PR) or complete response (CR). Postinduction patients with evidence of clinical disease progression are not eligible for preregistration.
  • Up to two regimens of therapy (conventional chemotherapy, antibody therapy, or an oral regimen) are allowed as long as a continuous response was ongoing throughout therapy. Overall, a partial response needs to have been achieved (using studies at the time of diagnosis as the baseline).
    • NOTE: For example, a patient who started treatment with rituximab/bendamustine and was then switched to R-CHOP (due to insufficient response or excessive toxicity) would be counted as having received 2 regimens.  However, R-CHOP alternating with R-DHAP as a planned induction regimen would count as one regimen.
  • Patient does not have any documented history of central nervous system (CNS) involvement by mantle cell lymphoma. This includes no evidence of parenchymal brain, spinal cord, or cerebrospinal fluid involvement. Radiculopathy symptoms from nerve root compression by lymphoma do not constitute CNS involvement.
  • Patient must have archived formalin-fixed paraffin-embedded (FFPE) tumor tissue specimen from the original diagnostic biopsy available for submission to Adaptive Biotechnologies for ClonoSEQ® ID molecular marker identification of unique  clonal immunoglobulin DNA sequence.
    • NOTE: If adequate tumor tissue is not available, peripheral blood collected prior to start of treatment with high disease burden (> 5%) is acceptable for molecular marker ID testing.  Adaptive Biotechnologies will forward results within fourteen (14) days of receipt of any stored (e.g., frozen or FFPE) tumor tissue specimen to the submitting institution and to the ECOG-ACRIN Operations Office.
    • NOTE: Patients for whom the molecular marker is identified will have peripheral blood collected after completion of induction (patient’s disease status is PR or CR) and submitted to Adaptive Biotechnologies for minimal residual disease (MRD) assessment.  Adaptive Biotechnologies will forward results within seven (7) days of receipt of fresh peripheral blood specimen to the submitting institution and to the ECOG-ACRIN Operations Office.

Eligibility Criteria for Treatment Assignment (STEP 1)

  • Patients must have met eligibility criteria for the screening step 0.
  • The proliferation rate, using Ki-67 or MIB-1 immunohistochemistry (≤ 30% versus > 30% versus indeterminate Ki-67 index), must be documented for a baseline tumor biopsy specimen.
  • Institution has received results from Adaptive Biotechnologies as defined by one of the following criteria:
    • Patients are MRD Indeterminate : ClonoSEQ® ID molecular marker assessment did not identify any unique clonal immunoglobulin DNA sequence; OR
    • ClonoSEQ® ID molecular marker assessment identified unique clonal immunoglobulin DNA sequence and MRD assessment is completed.
  • Patients must have completed induction therapy within 150 days prior to registration to Step 1, AND no more than 300 days may have elapsed from the first dose of induction chemotherapy (C1D1) given, until the last day of induction  chemotherapy administered. For those assigned to Arms A, C, or D, the date of transplant ( Day 0 ) must not be greater than 365 days after the first dose of induction chemotherapy (C1D1) given.
  • Patient must have received at least four (4) cycles of induction therapy.
  • Up to two regimens of therapy (conventional chemotherapy, antibody therapy, or an oral regimen) are allowed as long as a continuous response was ongoing throughout therapy.
    • NOTE: For example, a patient who started treatment with rituximab/bendamustine and was then switched to R-CHOP (due to insufficient response or excessive toxicity) would be counted as having received 2 regimens.  However, R-CHOP alternating with R-DHAP as a planned induction regimen would count as one regimen.
  • Patients must have achieved a radiologic complete or partial remission as defined by the Lugano Criteria.
  • In the opinion of the enrolling physician, patients must be felt to be a candidate for autologous stem cell transplantation.
  • Patients have an ECOG performance status of 0-2.
  • HIV positive patients are not excluded, but to enroll, must meet all of the below criteria:
    • HIV is sensitive to antiretroviral therapy;
    • Must be willing to take effective antiretroviral therapy that has minimal overlapping toxicity and pharmacokinetic interactions with protocol therapy;
    • No history of HIV-related opportunistic disease or AIDS defining conditions within past 12 months other than historic CD4+ T-cell counts below 200 cells/mm3;
    • Expected long-term survival if lymphoma were not present.
  • Patient must be disease-free ≥ 3 years of prior malignancies with the exception of adequately treated non-melanoma skin cancer, adequately treated in situ carcinoma, melanoma in situ post wide local excision or Mohs surgery, low grade prostate carcinoma (Gleason grade ≤ 6) managed with observation that has been stable for at least 6 months.
  • Women must not be pregnant or breast-feeding due to the potential for congenital abnormalities and of harm to nursing infants due to the treatment regimens used.  
  • All females 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 not undergone a hysterectomy or bilateral oophorectomy; or
    • has not been naturally postmenopausal 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 must be strongly advised to use an accepted and effective method of contraception or to abstain from sexual intercourse for the duration of their participation in the study and for 12 months post rituximab treatment.

 

Biologic/Vaccine, Other, Procedure/Surgery, Administration of antineoplastic agent, Drug therapy, Transplantation of autologous hematopoietic stem cell
Cancer, Lymphoma, Non-Hodgkin's lymphoma
Autologous stem cell transplant, Bone marrow transplant, Cancer treatment, Hematopoietic system, Mantle cell lymphoma, Medical Oncology, Rituximab, Targeted drug therapy, rituximab
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Multicenter trial for eliminating breast cancer surgery or radiotherapy in exceptional responders to neoadjuvant systemic therapy

Eliminating Breast Cancer Surgery in Exceptional Responders with Neoadjuvant Systemic Therapy

Judy Boughey
Female
30 years and over
Not Applicable
This study is NOT accepting healthy volunteers
0000-100303-P01-RST
18-002227
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Inclusion Criteria:

Patients may be enrolled prior to, during, or following neoadjuvant systemic therapy provided they meet the following eligibility and ineligibility requirements noted below:

  • Pathologically confirmed unicentric invasive breast cancer defined as radiologic clinical stage T1 or T2 (≤ 5 cm), N0 or N1 (≤ 4 abnormal axillary nodes on initial ultrasound), clinical stage M0.
  • HER2 positive (IHC 3+ and or FISH amplified) or triple receptor negative (TN, ER/PR < 10% HER2 negative (IHC 1+ or 2+ FISH non-amplified) receiving any standard routine clinical NST regimen.
  • Patient desires breast conserving therapy.
  • Age 40 years or older.  This age cutoff is justified because breast cancers in women under the age of 40 are known to have a significantly higher risk of IBTR presumably due to underlying biologic differences [104, 105].
  • Female sex.
  • If the patient has a history of a prior non-breast  cancer, all treatment for this cancer must have been completed prior to study registration and the patient must have no evidence of disease for this prior non-breast cancer.
  • Patient must have an initial nodal ultrasound that does not demonstrate more than four suspicious lymph nodes, any suspicious lymph nodes should be biopsied to determine if nodal metastatic disease present.


Exclusion Criteria:

  • Radiologic evidence for a stage T3 or clinical stage T4 breast cancer.
  • Clinical or pathologic evidence for distant metastases.
  • Prior diagnosis of invasive or ductal carcinoma in situ breast cancer in the ipsilateral breast.
  • Clinical evidence of progression of disease > 20% in the breast or new evidence of nodal metastases.
  • Patient is known to be pregnant.
  • Patient is participating in a NST protocol in which surgical excision of the breast and or lymph nodes are required.
Behavioral, Procedure/Surgery, Chemotherapy, Radiation therapy procedure or service, Radiation oncology AND/OR radiotherapy
Breast cancer, Cancer, Recurrent breast cancer
Breast cancer surgery, Cancer treatment, Chemotherapy, Chemotherapy for breast cancer, Malignant tumor of breast, Medical Oncology, Radiation therapy, Radiation therapy for breast cancer
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Randomized Phase II and Phase III Studies of Individualized Treatment for Nasopharyngeal Carcinoma Based on Biomarker Epstein Barr Virus (EBV) Deoxyribonucleic Acid (DNA)

Individualized Treatment in Treating Patients With Stage II-IVB Nasopharyngeal Cancer Based on EBV DNA

Katharine Price
All
18 years and over
Phase 2/3
This study is NOT accepting healthy volunteers
0000-100305-P01-RST
18-000158
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Inclusion Criteria:

  • Biopsy proven (from primary lesion and/or lymph nodes) diagnosis of cancer of the nasopharynx
  • Patients must have detectable pretreatment plasma EBV DNA, determined by the central lab prior to Step 2 registration
  • Stage II-IVB disease (American Joint Committee on Cancer [AJCC], 7th edition [ed.]) with no evidence of distant metastasis, based upon the following minimum diagnostic workup:
    • History/physical examination by a Medical Oncologist or Clinical Oncologist or Radiation Oncologist or Ear, Nose, Throat specialist (ENT), which must include an endoscopic evaluation, a complete list of current medications, and assessment of weight and weight loss in the past 6 months within 21 days prior to registration
    • Evaluation of tumor extent with magnetic resonance imaging (MRI) of the nasopharynx and neck within 28 days prior to registration; if MRI is medically contraindicated, obtain computed tomography (CT) scan with =< 3 mm contiguous slices with contrast and bone windows (to evaluate base of skull involvement); Note: If a treatment planning CT scan is used, it must be with =< 3 mm contiguous slices with contrast and be read by a radiologist
    • To rule out distant metastasis, patients must undergo the following imaging within 28 days prior to registration:
      • A CT scan with contrast of the chest, abdomen, and/or pelvis or a total body positron emission tomography (PET)/CT scan (non-contrast PET/CT is acceptable)
      • A bone scan only when there is suspicion of bone metastases (a PET/CT scan can substitute for the bone scan)
  • Zubrod performance status 0-1 within 21 days prior to registration
  • Absolute neutrophil count (ANC) >= 1,500 cells/mm^3
  • Platelets >= 100,000 cells/mm^3
  • Hemoglobin >= 8.0 g/dl (Note: the use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 8.0 g/dl is acceptable)
  • Total bilirubin =< 1.5 x institutional upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 1.5 x institutional ULN
  • Alkaline phosphatase =< 1.5 x institutional ULN
  • Serum creatinine =< 1.5 mg/dl or calculated creatinine clearance (CC) >= 50 ml/min determined by 24-hour urine collection or estimated by Cockcroft-Gault formula
  • Negative serum pregnancy test within 14 days prior to registration for women of childbearing potential
  • Women of childbearing potential and male participants who are sexually active must agree to use a medically effective means of birth control throughout protocol treatment
  • Patient must provide study specific informed consent prior to study entry, including the mandatory pre-treatment plasma EBV DNA assay


Exclusion Criteria:

  • Prior invasive malignancy (except node negative, non-melanomatous skin cancer) unless disease free for a minimum of 1095 days (3 years) (for example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible)
  • Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowable; however, at least 6-weeks recovery is necessary if the last regimen included nitrosourea or mitomycin
  • Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
  • Patients with hearing loss assessed to be primarily sensorineural in nature, requiring a hearing aid, or intervention (i.e. interfering in a clinically significant way with activities of daily living); a conductive hearing loss from tumor-related otitis media is allowed
  • >= Grade 2 peripheral sensory neuropathy (CTCAE, v. 4.0)
  • Severe, active co-morbidity, defined as follows:
    • Major medical or psychiatric illness, which in the investigator's opinion would interfere with the completion of therapy and follow up or with full understanding of the risks and potential complications of the therapy
    • Unstable angina and/or uncontrolled congestive heart failure
    • Myocardial infarction within the last 6 months
    • Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration; note that patients switched from IV antibiotics and currently on oral antibiotics whose infection is assessed to be adequately treated or controlled are eligible
    • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days prior to registration
    • Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that human immunodeficiency virus (HIV) testing is not required for entry into this protocol
  • Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception
  • Prior allergic reaction to the study drug(s) involved in this protocol
  • Patients with undetectable pre-treatment plasma EBV DNA

Drug, Radiation, Administration of antineoplastic agent, Drug therapy, Epstein-Barr virus serologic test, Radiation therapy procedure or service, Radiation oncology AND/OR radiotherapy
Cancer, Head and neck cancer, Nasal and paranasal tumors, Nasal cancer, Nasopharyngeal carcinoma, Throat cancer
1,2-Diaminocyclohexaneplatinum II citrate, Cancer treatment, Chemotherapy, Digestive system, Fluorouracil [USAN:USP:INN:BAN:JAN], Gemcitabine [USAN:INN:BAN], Infinnium, Malignant tumor of nasopharynx, Medical Oncology, Radiation therapy, Respiratory system, cisplatin, fluorouracil, gemcitabine, paclitaxel
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APEC1621, NCI-COG Pediatric MATCH (Molecular Analysis for Therapy Choice) (APEC1621)

Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients with Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorder

Wendy Allen-Rhoades
All
12 months to 21 years old
Phase 2
This study is NOT accepting healthy volunteers
0000-100311-P01-RST
18-000708
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Inclusion Criteria:

ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC:

  • Patients with recurrent or refractory solid tumors, including non-Hodgkin lymphomas, histiocytoses (e.g., langerhans cell histiocytosis [LCH], juvenile xanthogranuloma [JXG], histiocytic sarcoma), and central nervous system (CNS) tumors are eligible; patients must have had histologic verification of malignancy at original diagnosis or relapse except in patients with intrinsic brain stem tumors, optic pathway gliomas, or patients with pineal tumors and elevations of cerebrospinal fluid (CSF) or serum tumor markers including alpha-fetoprotein or beta-human chorionic gonadotropin (HCG); in cases where patient enrolls prior to histologic confirmation of recurrent disease, patient is ineligible and should be withdrawn from study if histology fails to confirm recurrence; please note: Patients with Hodgkin lymphoma and plexiform neurofibroma are not eligible.

ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC:

  • Patients must have an formalin-fixed paraffin-embedded (FFPE) tumor sample available for MATCH study testing from a biopsy or surgery that was performed at any point after initial tumor recurrence/progression, or be planned to have a procedure to obtain such a sample that is considered to be of potential benefit by the treating clinicians; a tumor sample from a clinically performed diagnostic (pre-treatment) biopsy will be acceptable for enrollment onto Pediatric MATCH only for children with high-grade gliomas of the brainstem (diffuse intrinsic pontine gliomas) or thalamus.
    • Note: Samples that have been decalcified using standardly utilized acid-based decalcification methods are not generally suitable for MATCH study testing; the nucleic acids will have been degraded in the decalcification process.
  • Karnofsky ≥ 50% for patients > 16 years of age and Lansky ≥ 50 for patients ≤ 16 years of age).
    • Note: neurologic deficits in patients with CNS tumors must have been stable for at least 7 days prior to study enrollment; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.

GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS:

  • Note: patient does not need to meet all subprotocol criteria at time of enrollment onto the APEC1621SC screening protocol, but will need to meet all criteria prior to enrollment on any assigned treatment subprotocol.
  • Patients must be enrolled onto a subprotocol within 12 weeks (84 days) of treatment assignment.

GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS:

  • Karnofsky ≥ 50% for patients > 16 years of age and Lansky ≥ 50 for patients ≤ 16 years of age).
    • Note: neurologic deficits in patients with CNS tumors must have been stable for at least 7 days prior to study enrollment; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.

GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS:

  • At the time of treatment with subprotocol specified therapy, the patients must have radiographically measurable disease; patients with neuroblastoma who do not have measurable disease but have iobenguane (MIBG) positive (+) evaluable are eligible; measurable disease in patients with CNS involvement is defined as tumor that is measurable in two perpendicular diameters on magnetic resonance imaging (MRI) and visible on more than one slice.
    • Note: The following do not qualify as measurable disease: 
      • Malignant fluid collections (e.g., ascites, pleural effusions);
      • Bone marrow infiltration except that detected by MIBG scan for neuroblastoma;
      • Lesions only detected by nuclear medicine studies (e.g., bone, gallium or positron emission tomography [PET] scans) except as noted for neuroblastoma;
      • Elevated tumor markers in plasma or CSF;
      • Previously radiated lesions that have not demonstrated clear progression post radiation;
      • Leptomeningeal lesions that do not meet the measurement requirements for Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS:

  • At the time of enrollment onto a subprotocol, the following general criteria for initiation of therapy will be required: 
    • Patients must have fully recovered from the acute toxic effects of all prior anticancer therapy and must meet the following minimum duration from prior anticancer directed therapy prior to enrollment to the subprotocol; if after the required timeframe, the numerical eligibility criteria are met; e.g., blood count criteria, the patient is considered to have recovered adequately;
    • Cytotoxic chemotherapy or other anticancer agents known to be myelosuppressive: for agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned research coordinator prior to enrollment ≥ 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy (42 days if prior nitrosourea);
    • Anticancer agents not known to be myelosuppressive (e.g., not associated with reduced platelet or absolute neutrophil counts [ANC]): ≥ 7 days after the last dose of agent; for agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned research coordinator prior to enrollment;
    • Antibodies: ≥ 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade ≤ 1;
    • Corticosteroids: If used to modify immune adverse events related to prior therapy, ≥ 14 days must have elapsed since last dose of corticosteroid;
    • Hematopoietic growth factors: ≥ 14 days after the last dose of a long-acting growth factor (e.g., Neulasta) or 7 days for short-acting growth factor; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair and the study-assigned research coordinator;
    • Interleukins, interferons and cytokines (other than hematopoietic growth factors): ≥ 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors);
    • Stem cell infusions (with or without total-body irradiation [TBI]): 
      • Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion (DLI) or boost infusion: ≥ 84 days after infusion and no evidence of graft versus host disease (GVHD);
      • Autologous stem cell infusion including boost infusion: ≥ 42 days.
    • Cellular therapy: ≥ 42 days after the completion of any type of cellular therapy (e.g., modified T cells, NK cells, dendritic cells, etc.).
    •  X-ray therapy (XRT)/External Beam Irradiation including Protons: ≥ 14 days after local XRT; ≥ 150 days after TBI, craniospinal XRT or if radiation to ≥ 50% of the pelvis; ≥ 42 days if other substantial bone marrow (BM) radiation.
      • Note: radiation may not be delivered to "measurable disease" tumor site(s) being used to follow response to subprotocol treatment.
    • Radiopharmaceutical therapy (e.g., radiolabeled antibody, 131I-MIBG): ≥ 42 days after systemically administered radiopharmaceutical therapy.

GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS:

  • For patients with solid tumors without known bone marrow involvement: 
    • Peripheral absolute neutrophil count (ANC)  ≥ 1000/mm^3;
    • Platelet count  ≥ 100,000/mm^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment).

GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS:

  • Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions); these patients will not be evaluable for hematologic toxicity

GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS:

  • Creatinine clearance or radioisotope glomerular filtration rate (GFR)  ≥ 70ml/min/1.73 m^2 or a serum creatinine based on age/gender as follows:
    • Age: 1 to < 2 years; maximum serum creatinine (mg/dL): male 0.6; female 0.6;
    • Age: 2 to < 6 years; maximum serum creatinine (mg/dL): male 0.8; female 0.8;
    • Age: 6 to < 10 years; maximum serum creatinine (mg/dL): male 1; female 1;
    • Age: 10 to < 13 years; maximum serum creatinine (mg/dL): male 1.2; female 1.2;
    • Age: 13 to < 16 years; maximum serum creatinine (mg/dL): male 1.5; female 1.4;
    • Age: ≥ 16 years; maximum serum creatinine (mg/dL): male 1.7; female 1.4.

GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS:

  • Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x upper limit of normal (ULN) for age. 

GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS:

  • Serum glutamate pyruvate transaminase (SGPT) (alanine transferase [ALT]) ≤ 135 U/L (for the purpose of this study, the ULN for SGPT is 45 U/L) 

GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS:

  • Patients must be able to swallow intact capsules/tablets, unless otherwise specified in the subprotocol to which they are assigned.

GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS:

  • Agent specific limitations on prior therapy will be included with specific treatment subprotocols.


Exclusion Criteria:
 

GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS:

  • Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies, or because there is currently no available information regarding human fetal or teratogenic toxicities; pregnancy tests must be obtained in females who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method. 

GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS:

  • Concomitant medications.
  • Corticosteroids: at the time of consent and enrollment to regimen specific subprotocols, patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment to the subprotocol will not be eligible; if used to modify immune adverse events related to prior therapy, ≥ 14 days must have elapsed since last dose of corticosteroid.
  • Investigational drugs: patients must meet criteria for prior therapy at the time of consent and enrollment to a subprotocol; other investigational agents may not be administered to patients while they are receiving study drug as part of a subprotocol.
  • Anticancer agents: patients must meet criteria for prior therapy at the time of consent and enrollment to a subprotocol; other investigational agents may not be administered to patients while they are receiving study drug as part of a subprotocol.
  • Anti-GVHD agents post-transplant: patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible.

GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS:

  • Patients who have an uncontrolled infection are not eligible.

GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS:

  • Patients who have had a prior solid organ transplant are not eligible. 

GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS:

  • Additional agent specific criteria will be included with specific treatment subprotocols
Drug, Procedure/Surgery, Other, Administration of antineoplastic agent, Drug therapy
Brain tumor, Cancer, Lymphoma, Neuroblastoma, Non-Hodgkin's lymphoma, Pediatric brain tumor
Cancer treatment, Hematopoietic system, Histiocytic neoplasm, Medical Oncology, Nervous system, Non-Hodgkin's lymphoma (clinical), Solid tumor configuration, palbociclib
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XL184-021 A Phase 1b Dose-Escalation Study of Cabozantinib (XL184) Administered Alone or in Combination With Atezolizumab to Subjects With Locally Advanced or Metastatic Solid Tumors

Study of Cabozantinib Alone or in Combination With Atezolizumab to Subjects With Locally Advanced or Metastatic Solid Tumors

Lance Pagliaro
All
18 years and over
Phase 1/2
This study is NOT accepting healthy volunteers
0000-100312-P01-RST
17-009273
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Inclusion Criteria:

  • Cytologically or histologically and radiologically confirmed solid tumor that is inoperable locally advanced, metastatic, or recurrent:

Dose-Escalation Stage:

  • Subjects with UC (including renal pelvis, ureter, urinary bladder, urethra) after prior platinum-based therapy, or
  • Subjects with RCC (clear cell, non-clear cell histology) with or without prior systemic anticancer therapy.

Expansion Stage:

  • Expansion Cohort 1: Subjects with RCC with clear cell histology (including those with mixed sarcomatoid component) and without prior systemic anticancer therapy.
  • Expansion Cohort 2: Subjects with UC with transitional cell histology (including renal pelvis, ureter, urinary bladder, urethra) who have radiographically progressed on or after platinum-containing chemotherapy including subjects who received prior neoadjuvant or adjuvant platinum-containing therapy with disease recurrence < 12 months from the end of last therapy.
  • Expansion Cohort 3: Subjects with UC with transitional cell histology (including renal pelvis, ureter, urinary bladder, urethra) who are ineligible for cisplatin-based chemotherapy and have not received prior systemic anticancer therapy for inoperable locally advanced or metastatic disease.
    • Ineligible for cisplatin-based chemotherapy is defined by meeting one of the following criteria:
    • Impaired renal function (glomerular filtration rate [GFR] < 60 mL/min/1.73 m2), hearing loss of ≥ 25 dB at two contiguous frequencies, or ≥ Grade 2 peripheral neuropathy per Common Terminology Criteria for Adverse Events (CTCAE) v4.
    • Prior neoadjuvant or adjuvant platinum-based chemotherapy is allowed if disease recurrence took place > 12 months from end of last therapy.
  • Expansion Cohort 4: Subjects with UC with transitional cell histology (including renal pelvis, ureter, urinary bladder, urethra) eligible for cisplatin-based chemotherapy and have not received prior systemic anticancer therapy for inoperable locally advanced or metastatic disease.
    • Prior neoadjuvant or adjuvant platinum-based chemotherapy is allowed if disease recurrence took place > 12 months from end of last therapy.
  • Expansion Cohort 5: Subjects with UC with transitional cell histology (including renal pelvis, ureter, urinary bladder, urethra) who have radiographically progressed on or after one prior immune checkpoint inhibitor (anti-PD-1 or anti-PD-L1) for the treatment of inoperable locally advanced or metastatic disease.
    • Allowed are up to 2 lines of prior systemic anticancer therapy to treat inoperable locally advanced or metastatic UC including prior treatment with an anti-CTLA-4 agent.
    • Excluded are subjects who had a prior combination therapy of an immune checkpoint inhibitor (anti-PD-1 or anti-PD-L1) with a VEGFR-targeting TKI.
  • Expansion Cohort 6: Subjects with metastatic CRPC (adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features) who have radiographically progressed in soft tissue on or after enzalutamide and/or abiraterone acetate for metastatic disease.
    • Note: prostate-specific antigen [PSA] progression or bone progression alone are not allowed to determine eligibility.
    • Prior chemotherapy is not allowed with the exception of docetaxel given in combination with androgen deprivation therapy (ADT) for progressive castration-sensitive disease prior to treatment with enzalutamide and/or abiraterone acetate.
    • Subject must have castrate-level testosterone (< 50 ng/dL [< 2 nM]) following bilateral orchiectomy or by ongoing androgen deprivation therapy with a gonadotropin-releasing hormone (GnRH) analog that was initiated ≥ 4 weeks prior to first dose of study treatment and must be continued throughout the study.
  • Expansion Cohort 7: Subjects with Stage IV non-squamous NSCLC who have radiographically progressed on or after treatment with one prior immune checkpoint inhibitor (anti-PD-1 or anti-PD-L1) for metastatic disease.
    • Allowed are up to 2 lines of prior systemic anticancer therapy to treat metastatic NSCLC including prior treatment with an anti-CTLA-4 agent.
    • Excluded are subjects who had a prior VEGFR-targeting TKI.
    • Excluded are subjects who have been diagnosed with an EGFR sensitizing mutation, ALK rearrangement, ROS1 rearrangement, or BRAF V600E mutation.
  • Expansion Cohort 8: Subjects with Stage IV non-squamous NSCLC with positive PD-L1 expression (TC ≥ 1% [TC = tumor cell]) and without prior systemic anticancer therapy for metastatic disease.
    • Acceptable reports for prior PD-L1 expression testing by immunohistochemical (IHC) assessment include the following:
      • US sites: FDA-approved Dako PD-L1 IHC 22C3 pharmDx assay;
      • Ex-US sites: health authority-approved or CE-marked Dako PD-L1 IHC 22C3 pharmDx assay.
    • A prior local laboratory PD-L1 report using a validated assay may be accepted if slides can be provided to the central laboratory to assess PD-L1 expression using the FDA-approved Dako PD-L1 IHC 22C3 pharmDx assay.
    • Excluded are subjects who have been diagnosed with an EGFR sensitizing mutation, ALK translocation, ROS1 rearrangement, or BRAF V600E mutation.
  • Expansion Cohort 9: Subjects with Stage IV nonsquamous NSCLC with documentation of a sensitizing EGFR mutation who have radiographically progressed during or following prior treatment with an EGFR targeting TKI (e.g., osimertinib, gefitinib, erlotinib, afatinib) for metastatic disease.
    • There is no limit on the number of prior lines of systemic anticancer therapy including chemotherapy for inoperable locally advanced, recurrent, or metastatic disease.
    • Prior treatment with ICIs (anti-PD-1 or anti-PD-L1) is allowed if given in combination with chemotherapy.
  • Expansion Cohort 10: Subjects with RCC with non-clear cell histology (including those with sarcomatoid component)
    • Allowed is prior therapy with up to one VEGFR-targeting TKI (eg, sunitinib, pazopanib) for inoperable locally advanced, recurrent, or metastatic disease.
    • TKIs targeting MET or prior therapy with immune checkpoint inhibitors is not allowed.
  • Expansion Cohort 15: Subjects with gastric or gastroesophageal junction adenocarcinoma who have radiographically progressed during or following platinum-containing or fluoropyrimidine-containing chemotherapy for inoperable locally advanced, recurrent, or metastatic disease.
    • Allowed are up to 2 lines of prior systemic anticancer therapy for inoperable locally advanced, recurrent, or metastatic disease.
    • Prior HER-2/neu directed therapy is allowed if given combined with systemic chemotherapy.
  • Expansion Cohort 16: Subjects with colorectal adenocarcinoma who have radiographically progressed during or following systemic chemotherapy that contained fluoropyrimidine in combination with oxaliplatin or irinotecan for metastatic disease.
    • Allowed are up to 2 lines of prior systemic anticancer therapy for inoperable locally advanced, recurrent, or metastatic disease.
    • Prior EGFR-targeted therapy given with concurrent chemotherapy is allowed.
    • Subjects with known microsatellite instability-high (MSI-H) and/or mismatch repair (MMR) deficient disease are excluded.

Exploratory Single-Agent Cabozantinib (SAC) Cohorts:

  • Single-Agent Cohort 19: Subjects with UC with transitional cell histology (including renal pelvis, ureter, urinary bladder, urethra) who have radiographically progressed on or after one prior ICI (anti-PD-1 or anti-PD-L1) for the treatment of inoperable locally advanced or metastatic disease.
    • Allowed are up to 2 lines of prior systemic anticancer therapy to treat inoperable locally advanced or metastatic UC including prior treatment with an anti-CTLA-4 agent.
    • Excluded are subjects who had a prior combination therapy of an immune checkpoint inhibitor (anti-PD-1 or anti-PD-L1) with a VEGFR-targeting TKI.
  • Single-Agent Cohort 20: Subjects with Stage IV non-squamous NSCLC who have radiographically progressed on or after treatment with one prior ICI (anti-PD-1 or anti-PD-L1) for metastatic disease.
    • Allowed are up to 2 lines of prior systemic anticancer therapy to treat metastatic NSCLC including prior treatment with an anti-CTLA-4 agent.
    • Excluded are subjects who had a prior combination therapy of an immune checkpoint inhibitor (anti-PD-1 or anti-PD-L1) with a VEGFR-targeting TKI and subjects who have been diagnosed with an EGFR sensitizing mutation, ALK translocation, ROS1 rearrangement, or BRAF V600E mutation.
  • Exploratory Single-Agent Cabozantinib (SAC) Cohort 21, Exploratory Single-AgentAtezolizumab (SAA) Cohort 22, and Combination-Therapy Expansion Cohort 23:Subjects with metastatic CRPC who have histologically or cytologically confirmedadenocarcinoma of the prostate without small cell component (Note: Neuroendocrinedifferentiation and other histologic components are permitted if adenocarcinoma is theprimary histology) with the following requirements:
    • Prior treatment with one, and only one, NHT (eg, abiraterone, apalutamide,darolutamide, or enzalutamide) for castration-sensitive locally advanced (T3 or T4) ormetastatic castration-sensitive prostate cancer (mCSPC), M0 CRPC, or mCRPC. Note: Subjects may have previously received taxane-based chemotherapy for mCSPCbut no other approved or experimental nonhormonal systemic therapies formetastatic prostate cancer.
    • Bilateral orchiectomy or ongoing androgen deprivation therapy with a GnRHagonist/antagonist (surgical or medical castration), with serum testosterone≤ 50 ng/dL (≤ 1.73 nmol/L) at screening.
    • Progressive disease at study entry as defined by at least one of the following two criteria:
      • a. PSA progression defined by a minimum of 2 rising PSA values from 3 or 4 consecutive assessments with an interval of at least 7 days between assessments.The most recent qualifying PSA value must be drawn within 28 days of plannedenrollment. (Note: If qualifying solely by PSA progression, the screening central lab PSA value must be at least 2 ng/mL [2 μg/L] but need not serve as last PSA value for determination of PSA progression; up to one PSA decrease is permitted as long as it is not the most recent value), OR
      • Soft tissue disease progression in the opinion of the Investigator. Note: Bone disease progression alone does not qualify.

• High risk metastatic disease per Investigator read as defined by at least one of the
following:

  • Measurable visceral disease (eg, adrenal, kidney, liver, lung, pancreas, spleen), OR
  • Measurable extrapelvic adenopathy (ie, adenopathy above the aortic bifurcation)
  • Combination-Therapy Expansion Cohort 24: Subjects with metastatic CRPC who have histologically or cytologically confirmed adenocarcinoma of the prostate without small cell component (Note: Neuroendocrine differentiation and other histologic componentsare permitted if adenocarcinoma is the primary histology) with the following requirements:
    • Prior taxane-based chemotherapy initiated for mCRPC (Note: Subjects may have previously received taxane-based chemotherapy for CSPC but no other approved or experimental nonhormonal systemic therapies for metastatic prostate cancer.)
    • Prior treatment with at least one NHT (eg, abiraterone, apalutamide, darolutamide, or enzalutamide) for castration-sensitive locally advanced (T3 or T4) or metastatic castration-sensitive prostate cancer (mCSPC), M0 CRPC, or mCRPC.
    • Bilateral orchiectomy or ongoing androgen deprivation therapy with a GnRH agonist/antagonist (surgical or medical castration), with serum testosterone ≤ 50 ng/dL (≤ 1.73 nmol/L) at screening.
    •  Progressive disease at study entry as defined by at least one of the following two criteria:
      •  Prostate specific antigen (PSA) progression defined by a minimum of 2 rising PSA values from 3 or 4 consecutive assessments with an interval of at least 7 days between assessments. The most recent qualifying PSA value must be drawn within 28 days of planned enrollment. (Note: If qualifying solely by PSA progression, the screening central lab PSA value must be at least 2 ng/mL [2 μg/L] but need not serve as last PSA value for determination of PSA progression; up to one PSA decrease is permitted as long as it is not the mostrecent value), OR
      • Soft tissue disease progression in the opinion of the Investigator. Note: Bone disease progression alone does not qualify.
    • High risk metastatic disease per Investigator read as defined by at least one of the following:
      • Measurable visceral disease (eg, adrenal, kidney, liver, lung, pancreas, spleen, but not bladder or other pelvic structure) OR
      • Measurable extrapelvic adenopathy (ie, adenopathy above the aortic bifurcation)
  • Measurable disease per RECIST 1.1 as determined by the investigator. Measurable disease must be outside the radiation field if prior radiation therapy was administered.
  • Tumor tissue material available (archival or recent tumor biopsy).
  • Recovery to baseline or ≤ Grade 1 CTCAE v4 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy.
  • Age eighteen years or older on the day of consent.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
  • Adequate organ and marrow function, based upon meeting all of the following laboratory criteria within 14 days before first dose of study treatment:
    • Absolute neutrophil count (ANC) ≥ 1500/mm3 (≥ 1.5 GI/L) without granulocyte colony-stimulating factor support within 2 weeks before screening laboratory sample collection.
    • White blood cell count ≥ 2500/mm3 (≥ 2.5 GI/L).
    • Platelets ≥ 100,000/mm3 (≥ 100 GI/L) without transfusion within 2 weeks before screening laboratory sample collection. For subjects with HCC ≥ 75,000/mm3 (≥ 75 GI/L).
    • Hemoglobin ≥ 9 g/dL (≥ 90 g/L) without transfusion within 2 weeks before screening laboratory sample collection.
    • Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) ≤ 3 × upper limit of normal (ULN). ALP ≤ 5 × ULN with documented bone metastases. For subjects with HCC: ALT, AST, and ALP ≤ 5 × ULN.  For subjects with mCRPC with documented bone metastases: ALT ≤ 3 × ULN, AST ≤ 3 × ULN, and ALP ≤ 10 × ULN. If ALP > 5 × ULN in mCRPC subjects, then it must be demonstrated that it is predominantly bone-specific ALP.
    • Total bilirubin ≤ 1.5 × ULN (for subjects with Gilbert’s disease ≤3 × ULN). For subjects with HCC ≤ 2 mg/dL (≤ 34.2 μmol/L).
    • Serum creatinine ≤ 1.5 × ULN or calculated creatinine clearance ≥ 40 mL/min (≥ 0.67 mL/sec) using the Cockcroft-Gault equation (see Table 5-2 for Cockcroft-Gault formula).
    • Urine protein/creatinine ratio (UPCR) ≤ 1 mg/mg (≤ 113.2 mg/mmol). For subjects with UC: ≤ 2 mg/mg (≤ 226.4 mg/mmol) creatinine.
  • Capable of understanding and complying with the protocol requirements and must have signed the informed consent document.
  • Sexually active fertile subjects and their partners must agree to use highly effective methods of contraception that alone or in combination result in a failure rate of less than 1% per year when used consistently and correctly during the course of the study and for 5 months after the last dose of study treatment.  An additional contraceptive method, such as a barrier method (eg, condom), is recommended.
  • Female subjects of childbearing potential must not be pregnant at screening. Female subjects are considered to be of childbearing potential unless one of the following criteria are met: permanent sterilization (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or documented postmenopausal status (defined as 12 months of amenorrhea in a woman over 45 years-of-age in the absence of other biological or physiological causes. In addition, females under 55 years-of-age must have a serum follicle stimulating hormone (FSH) level > 40 mIU/mL to confirm menopause). Note: Documentation may include review of medical records, medical examination, or medical history interview by study site staff.


Exclusion Criteria:

  • Prior treatment with cabozantinib or ICIs including anti-CTLA-4, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-OX-40, anti-CD137 therapy except for Expansion Cohorts 5 and 7 and SAC Cohorts 19 and 20 in which prior anti-PD-1 or anti-PD-L1 therapy is required for eligibility (see Inclusion Criteria 1g, 1i, 1u, and 1v, respectively, for details).
  • Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before first dose of study treatment.
  • For CRPC subjects: receipt of abiraterone within 1 week before first dose of study treatment or receipt of any other androgen-receptor inhibitors within 2 weeks before first dose of study treatment.
  • HCC subjects who meet any of the following criteria are ineligible:
    • a. Received prior local anticancer therapy (including embolization and ablation) within 4 weeks before first dose of study treatment. For prior radiation for bone metastases, refer to Exclusion Criteria 6.
    • b. Subjects with fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma.
  • Receipt of any type of anticancer antibody (including investigational antibody) or systemic chemotherapy within 4 weeks before first dose of study treatment, except in Expansion Cohorts 5 and 7 and SAC Cohorts 19 and 20 for which receipt of a PD-1, PD-L1, or CTLA-4 targeting antibody is permitted within 4 weeks before first dose of study treatment.
  • Radiation therapy for bone metastasis within 2 weeks, any other local radiation therapy within 4 weeks before first dose of study treatment. Subjects who have received systemic treatment with radionuclides within 6 weeks before first dose of study treatment are not eligible. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible.
  • Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks before first dose of study treatment. Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of first dose of study treatment.
  • Concomitant anticoagulation with oral anticoagulants except for those specified below.
    • Allowed anticoagulants are:
      • Prophylactic use of low-dose aspirin for cardioprotection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH).
      • Therapeutic doses of LMWH or specified direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban in subjects (excluding HCC subjects) without known brain metastases who are on a stable dose of the anticoagulant for at least 1 week before first dose of study treatent and without clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor. Note: Subjects with HCC may be treated with therapeutic LMWH but must have a screening platelet count > 100,000/μL. Direct inhibitors of thrombin or factor Xa are not permitted in subjects with HCC.
  • Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 2 weeks prior to first dose of study treatment. Inhaled and topical corticosteroids and mineralocorticoids are allowed.
  • Administration of a live, attenuated vaccine within 30 days before first dose of study treatment.
  • The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
    • Cardiovascular disorders:
      • Congestive heart failure New York Heart Association Class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias.
      • Uncontrolled hypertension defined as sustained blood pressure (BP) > 140 mm Hg systolic or > 90 mm Hg diastolic despite optimal antihypertensive treatment.
      • Stroke (including transient ischemic attack [TIA]), myocardial infarction (MI), or other ischemic event, or thromboembolic event (eg, deep venous thrombosis [DVT], pulmonary embolism) within 6 months before first dose. Subjects with a diagnosis of DVT within 6 months are allowed if stable, asymptomatic, and treated with LMWH for at least 6 weeks before first dose.
    • Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation:
      • Tumors invading the GI-tract, active peptic ulcer disease, inflammatory bowel disease, diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis or acute obstruction of the pancreatic or biliary duct, or gastric outlet obstruction.  Presence of primary GI tumor is not excluded.
      • Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess within 6 months before first dose. Note: Complete healing of an intra-abdominal abscess must be confirmed before first dose
      • Gastric or esophageal varices that are untreated or incompletely treated with bleeding or high risk for bleeding. Subjects treated with adequate endoscopic therapy (according to institutional standards) without any episodes of recurrent GI bleeding requiring transfusion or hospitalization for at least 6 months prior to study entry are eligible.
    • Clinically significant hematuria, hematemesis, or hemoptysis of > 0.5 teaspoon (2.5 mL) of red blood, or other history of significant bleeding (eg, pulmonary hemorrhage) within 12 weeks before first dose.
    • Cavitating pulmonary lesion(s) or known endobronchial disease manifestation.
    • Lesion invading a major blood vessel including, but not limited to, inferior vena cava, pulmonary artery, or aorta. HCC subjects with lesions invading the hepatic portal vasculature are eligible.
    • Other clinically significant disorders such as:
      • Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, psoriatic arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren’s syndrome, Guillain-Barré syndrome, or multiple sclerosis. Subjects with the following conditions are eligible for the study:
        • A history of autoimmune-related hypothyroidism and on thyroid replacement hormone therapy
        • Controlled Type 1 diabetes mellitus and on an insulin regimen
        • Asthma
        • Eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only provided all of following are true:
        • Rash covers < 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
      • Active infection requiring systemic treatment, infection with human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness, acute or chronic hepatitis B or C infection in non-HCC tumor cohorts, or positive test for tuberculosis.  Subjects with history of COVID-19 must have recovered from the disease at least 30 days prior to enrollment.
      • History of idiopathic pulmonary fibrosis, organizing pneumonia (eg, bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computerized tomography (CT) scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
      • Serious non-healing wound/ulcer/bone fracture.
      • Malabsorption syndrome.
      • For all subjects except Cohort 18 (DTC): Free thyroxine (FT4) outside the laboratory normal reference range. Asymptomatic subjects with FT4 abnormalities can be eligible after sponsor approval.
      • Moderate to severe hepatic impairment (Child-Pugh B or C; Appendix K).
      • Requirement for hemodialysis or peritoneal dialysis.
      • History of solid organ or allogenic stem cell transplant.
  • Major surgery (e.g., GI surgery, removal or biopsy of brain metastasis) within 4 weeks or minor surgery (eg, simple excision, tooth extraction) within 10 days before first dose of study treatment. Complete wound healing from surgery must have occurred before first dose. Subjects with clinically relevant ongoing complications from prior surgery are not eligible.
  • Corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms per electrocardiogram (ECG) within 14 days before first dose of study treatment (see Section 5.6.4 for Fridericia formula).
    • Note: If a single ECG shows a QTcF with an absolute value > 500 ms, two additional ECGs at intervals of approximately 3 min must be performed within 30 min after the initial ECG, and the average of these  three consecutive results for QTcF will be used to determine eligibility (ie, if the average is ≤ 500 ms the subject is eligible).
  • Pregnant or lactating females.
  • Inability to swallow tablets.
  • Previously identified allergy or hypersensitivity to components of the study treatment formulations. Subjects with a history of infusion-related reaction to prior therapy with atezolizumab may be eligible by sponsor approval if the reaction was considered mild and manageable with appropriate supportive care (eg, use of premedication according to standard of care).
  • Diagnosis of another malignancy within 2 years before first dose of study treatment, except for superficial skin cancers, or localized, low grade tumors deemed cured and not treated with systemic therapy. Incidentally diagnosed prostate cancer is allowed if assessed as stage ≤ T2N0M0 and Gleason score ≤ 6.

 

Biologic/Vaccine, Drug, Administration of antineoplastic agent, Drug therapy
Bladder cancer, Cancer, Lung cancer, Non-small cell lung cancer, Prostate cancer, Ureteral cancer
Atezolizumab, Biological therapy for cancer, Cabozantinib, Cancer treatment, Chemotherapy, Medical Oncology, Reproductive system, Respiratory system, Solid tumor configuration, Targeted drug therapy, Urinary system, atezolizumab, cabozantinib
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CA224-020: A Phase I/2a Dose Escalation and Cohort Expansion Study of the Safety, Tolerability, and Efficacy of Anti-LAG-3 Monoclonal Antibody (BMS-986016) Administered Alone and in Combination With Anti-PD-1 Monoclonal Antibody (Nivolumab, BMS-936558) in Advanced Solid Tumors

An Investigational Immuno-therapy Study to Assess the Safety, Tolerability and Effectiveness of Anti-LAG-3 With and Without Anti-PD-1 in the Treatment of Solid Tumors

Matthew Block
All
18 years and over
Phase 1/2
This study is NOT accepting healthy volunteers
0000-100328-P01-RST
17-010030
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Inclusion Criteria:

  • For Dose escalation: subjects with cervical, ovarian, bladder and colorectal cancer (CRC), head and neck, gastric and hepatocellular cancer naive to immuno-oncology agents; 1st line melanoma and 1st line/2nd line NSCLC; Renal Cell Carcinoma naive to IO; NSCLC progressing while on or after therapy with anti-PD1/anti-PDL-1 and melanoma subjects progressed while-on or after treatment with anti-PD1 or anti-PDL1 with or without anti-CTLA-4.
  • For Dose Expansion: all of the above in escalation except for cervical, ovarian, and CRC
  • Progressed, or been intolerant to, at least one standard treatment regimen, except for subjects in 1st line cohorts.
  • ECOG performance status of 0 or 1
  • At least 1 lesion with measurable disease at baseline
  • Availability of an existing tumor biopsy sample (and consent to allow pre-treatment tumor biopsy)


Exclusion Criteria:

  • Primary central nervous system (CNS) tumors or solid tumors with CNS metastases as the only site of active disease
  • Autoimmune disease
  • Encephalitis, meningitis, or uncontrolled seizures in the year prior to informed consent
  • Uncontrolled CNS metastases

Biologic/Vaccine, Administration of antineoplastic agent, Drug therapy, Immunotherapy for cancer
Bladder cancer, Cancer, Cervical cancer, Colon cancer, Head and neck cancer, Hepatocellular carcinoma, Kidney cancer, Liver cancer, Lung cancer, Melanoma, Non-small cell lung cancer, Ovarian cancer, Rectal cancer, Skin cancer, Stomach cancer
Biological therapy for cancer, Cancer treatment, Digestive system, Integumentary system, MDX-1106, Malignant neoplastic disease, Medical Oncology, Relatlimab [USAN], Reproductive system, Respiratory system, Solid tumor configuration, Urinary system, nivolumab
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A Phase 2 Study of Poziotinib in Patients With Non-Small Cell Lung Cancer, Locally Advanced or Metastatic, With EGFR or HER2 Exon 20 Insertion Mutation (POZITIVE20-1)

A Study of Poziotinib in Patients with NSCLC With EGFR or HER2 Exon 20 Insertion Mutation

Julian Molina
All
18 years and over
Phase 2
This study is NOT accepting healthy volunteers
0000-100329-P01-RST
17-009282
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Inclusion Criteria:

  • Patient is at least 18 years of age.
  • Patient must be willing and capable of giving written Informed Consent, adhering to dosing and visit schedules, and meeting all study requirements.
  • Patient has histologically or cytologically confirmed locally advanced or metastatic non-small cell lung cancer (NSCLC) that is not amenable to treatment with curative intent.
  • Prior treatment status:
    • Cohorts 1 and 2: Patient has had at least one prior systemic treatment for locally advanced or metastatic NSCLC;
    • Cohorts 3 and 4: Patient is treatment-naïve for locally advanced or metastatic NSCLC and eligible to receive first-line treatment with poziotinib as determined by the Investigator. Adjuvant/neo-adjuvant therapies (chemotherapy, radiotherapy, or investigational agents) are permissible as long as they end at least 15 days prior to study entry;
    • Cohort 5: Patients who meet the criteria for enrollment in Cohort 1 to 4, but the enrollment in the respective cohort has been closed;
    • Cohort 6: Patients with EGFR mutation-positive NSCLC who progressed while on treatment with first-line osimertinib;
    • Cohort 7: Patient has had at least one prior systemic treatment for locally advanced or metastatic NSCLC.
  • Tissue and plasma samples for mutation confirmation:
    • Cohorts 1 to 5: Patient has adequate tumor tissue obtained from a biopsy or surgical procedure to enable molecular profiling for retrospective central laboratory confirmation of the mutation. If tissue is not available, the patient must have biopsy accessible disease and must be willing to undergo a biopsy to provide an appropriate tissue sample prior to receiving treatment in the study;
    • Cohort 6: A tissue sample must be provided after osimertinib progression;
    • Cohort 7: Either tissue or plasma samples are acceptable for enrollment.
  • Patient is positive for EGFR or HER2 mutations based on:
    • Cohorts 1 and 3: Documented EGFR exon 20 insertion mutation (including duplication mutations) using a next generation sequencing diagnostic test, such as OncoMine Comprehensive Assay (OCA) or FoundationOne Assay, or by an FDA approved test (eg, cobas® EGFR mutation test v2 or therascreen EGFR RGQ PCR kit) performed by a US CLIA certified and locally licensed clinical laboratory or similarly accredited lab for ex-US sites using tissue samples;
    • Cohorts 2 and 4: Documented HER2 exon 20 insertion mutation (including duplication mutations) using a next generation sequencing diagnostic test, such as OncoMine Comprehensive Assay (OCA) or FoundationOne Assay, performed by a US CLIA certified and locally licensed clinical laboratory or similarly accredited lab for ex-US sites using tissue samples;
    • Cohort 5: Documented EGFR or HER2 exon 20 insertion mutations using tissue samples using the criteria described for Cohorts 1 to 4;
    • Cohort 6: Documented acquired EGFR mutation who have progressed while on first-line osimertinib treatment using tissue tested with a next-generation sequencing assay;
    • Cohort 7: Documented EGFR or HER2 activating mutations (see table below) using tissue tested with a next-generation sequencing assay or plasma tested with a Guardant assay.
  • Patient has measurable NSCLC disease, as per the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1). Metastatic lesions in CNS or in brain cannot be used for target lesions.
  • Brain metastases may be allowed if patient’s condition is stable, defined as clinically asymptomatic, no requirement for high dose or increasing dose of systemic corticosteroids, and no need for any anticonvulsant therapy for metastatic brain disease. For the patient who has had radiation therapy, sequential post-treatment MRI tests, at least 4-6 weeks apart, should show no increases in brain lesion size/volume within 4 weeks prior to the study.
  • Patient has an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 and has a life-expectancy of more than 6 months.
  • Patient has recovered from prior systemic therapy for metastatic disease to Grade ≤1 for non-hematologic toxicities (except for Grade ≤ 2 peripheral neuropathy) and has adequate hematologic, hepatic, and renal function at Baseline, as defined by:
    • Leukocytes ≥ 3.0×10^9/L;
    • Absolute neutrophil count (ANC) must be ≥ 1.5×10^9/L;
    • Platelet count ≥ 100×10^9/L;
    • Hemoglobin ≥ 9.0 g/dL;
    • Total bilirubin ≤ 2 mg/dL; if hepatic metastases are present, ≤ 2.5 × ULN;
    • SGOT (AST) and SGPT (ALT) ≤ 2.5×ULN with the following exception; Patients with liver metastases AST, ALT ≤ 5×ULN;
    • Creatinine clearance ≥ 50 mL/min according to the Cockcroft-Gault equation;
    • Patient is willing to practice 2 forms of contraception, one of which must be a barrier method, from study entry until at least 30 days after the last dose of poziotinib;
    • Females of childbearing potential must have a negative pregnancy test within 30 days prior to enrollment. Females who are postmenopausal for at least 1 year (defined as more than 12 months since last menses) or who are surgically sterilized do not require this test.


Exclusion Criteria:

  • Patient has:
    • All Cohorts: EGFR T790M;
    • Cohorts 1 to 5: EGFR exon 20 point mutation;
    • Cohort 7: EGFR Exon 19 deletion and L858R or HER2 T798I mutations, EGFR and HER2 Exon 20 insertion mutation.
  • Patient has had previous treatment with poziotinib or any other EGFR or HER2 exon 20 insertion mutation-selective tyrosine kinase inhibitor (TKI) prior to study participation. The currently approved TKIs (ie, erlotinib, gefitinib, afatinib, osimertinib) are not considered to be exon 20 insertion-selective and are permissible (Cohorts 1 to 4).
  • Patient is concurrently receiving chemotherapy, biologics, immunotherapy for cancer treatment; systemic anti-cancer treatment or investigational treatment should not be used within 2 weeks; local radiation therapy for bone pain may be allowed.
  • Patient has a history of congestive heart failure (CHF) Class III/IV according to the New York Heart Association (NYHA) Functional Classification or serious cardiac arrhythmias requiring treatment.
  • Patient has a high risk of cardiac disease, as determined by the Investigator, may undergo either echocardiogram (ECHO) or multi-gated acquisition (MUGA) during Screening and has a cardiac ejection fraction < 50%.
  • Patient has had other malignancies within the past 3 years, except for stable non-melanoma skin cancer, fully-treated and stable, early-stage prostate cancer, or carcinoma in situ of the cervix or breast without need of treatment.
  • Patient is confirmed to have clinically significant or recent acute gastrointestinal disease presenting as diarrhea and/or coloenteritis as a main symptom (ie, acute enteritis, malabsorption, or Common Terminology Criteria for Adverse Events (CTCAE, version 4.03) Grade 2 or above diarrhea due to other etiologies).
  • Patient has an active Grade ≥ 2 skin disorder, rash, mucositis, or skin infection that needs medication or therapy or existing Grade ≥ 2 skin toxicity from previous therapies; Grade ≥ 2 neuropathy, Grade ≥ 2 pneumonitis.
  • Patient is unable to take drugs orally due to disorders or diseases that may affect gastrointestinal function, such as inflammatory bowel diseases (e.g., Crohn’s disease, ulcerative colitis) or malabsorption syndrome, or procedures that may affect gastrointestinal function, such as gastrectomy, enterectomy, or colectomy.
  • Patient has an active liver disease or biliary tract disease (except for Gilbert’s disease, asymptomatic biliary stones, liver metastasis, or stabilized chronic liver diseases).
  • Patient has known hypersensitivity to poziotinib or has a history of allergic reactions attributed to chemically similar compounds or other tyrosine kinase inhibitors (TKIs).
  • Patient has an active uncontrolled infection, underlying medical condition, or other serious illness that would not be appropriate for this study.
  • Patient has unstable, uncontrolled, active bleeding disorders that the investigator considers that the patient could be at increased risk or not be suitable for treatment in this study.
  • Patient is pregnant or breast-feeding.
  • Cohort 5 only: Patient is eligible for treatment in an open cohort (Cohorts 1 to 4).

 

Drug, Administration of antineoplastic agent, Drug therapy
Cancer, Lung cancer, Non-small cell lung cancer
Cancer treatment, Medical Oncology, Non-small cell lung cancer with mutation in epidermal growth factor receptor, Poziotinib, Respiratory system
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GC-LTFU-001 - Long-Term Follow-up Protocol for Subjects Treated With Gene-Modified T Cells

Long-Term Follow-up Protocol for Subjects Treated With Gene-Modified T Cells

Yi Lin
All
18 years and over
Phase 2/3
This study is NOT accepting healthy volunteers
0000-100331-P01-RST
17-011220
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Inclusion Criteria:

Subjects who meet the following criteria will be eligible to participate in the Long-Term Follow-Up study:

  • All adult and pediatric subjects who received at least one GM T cells infusion in a previous Celgene sponsored or Celgene alliance partner sponsored study, and have discontinued, or completed the post-treatment follow-up period in the parent treatment protocol, as applicable.
  • Subject (and, parental/legal representative, when applicable) must understand and voluntarily sign an Informed Consent Form/Informed Assent Form prior to any study-related assessments/procedures being conducted.
  • Subject is willing and able to adhere to the study visit schedule and other protocol requirements.


Exclusion Criteria:

  • None.
Genetic, Administration of antineoplastic agent, Drug therapy, Immunotherapy for cancer
Cancer
Biological therapy for cancer, Cancer treatment, Gene therapy, Malignant neoplastic disease, Medical Oncology
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ACNS1422, A Phase 2 Study of Reduced Therapy for Newly Diagnosed Average-Risk WNT-Driven Medulloblastoma Patients (ACNS1422)

Reduced Craniospinal Radiation Therapy and Chemotherapy in Treating Younger Patients With Newly Diagnosed WNT-Driven Medulloblastoma

Jonathan Schwartz
All
3 years to 21 years old
Phase 2
This study is NOT accepting healthy volunteers
0000-100349-P01-RST
17-009225
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Inclusion Criteria:

  • Patients must be greater than or equal to 3 years and less than 22 years of age at the time of enrollment.
  • Patients must be newly diagnosed and have:
    • Eligibility confirmed by rapid central pathology and molecular screening review on APEC14B1:
      • classical histologic type (non LC/A) WNT medulloblastoma;
      • positive nuclear β-catenin by IHC;
      • positive for CTNNB1 mutation;
      • negative for MYC and MYCN by FISH.
  • Patient must have negative lumbar CSF cytology.
    • Note: CSF cytology for staging should be performed no sooner than 14 days post operatively to avoid false positive CSF. Ideally, CSF should be obtained between Day 14 and Day 21 to allow for final staging status before enrollment onto the study. Patients with positive CSF cytology obtained 0 to 14 days after surgery should have cytology repeated to determine eligibility and final CSF status.  Patients with negative CSF cytology from lumbar puncture obtained 0 to 14 days after surgery do not need cytology repeated. Patients with negative CSF cytology from lumbar puncture obtained prior to surgery do not need cytology repeated post-operatively.
  • Patients must have eligibility confirmed by Rapid Central Imaging Review on APEC14B1. Patients must have ≤ 1.5 cm2 maximal cross-sectional area of residual tumor (see Section 3.1.4). Whole brain MRI with and without gadolinium and spine MRI with gadolinium must be performed.
  • Patients must be enrolled, and protocol therapy must be projected to begin, no later than 36 days after definitive diagnostic surgery (Day 0). 
  • Adequate Bone Marrow Function Defined As:
    • Peripheral absolute neutrophil count (ANC) ≥ 1000/μL;
    • Platelet count ≥ 100,000/μL (transfusion independent);
    • Hemoglobin ≥ 8.0 g/dL (may receive RBC transfusions).
  • Adequate Renal Function Defined As:
    • Creatinine clearance or radioisotope GFR ≥ 70 mL/min/1.73 m^2; or
    • A serum creatinine based on age/gender as follows:
      • Age | Maximum Serum Creatinine (mg/dL) | Male | Female
      • 3 to < 6 years | 0.8 | 0.8
      • 6 to < 10 years | 1.0 | 1.0
      • 10 to < 13 years | 1.2 | 1.2
      • 13 to < 16 years | 1.5 | 1.4
      • ≥ 16 years | 1.7 | 1.4
    • The threshold creatinine values in this Table were derived from the Schwartz formula for estimating GFR (Schwartz et al. J. Peds, 106:522, 1985) utilizing child length and stature data published by the CDC.
  • Adequate Liver Function Defined As:
    • Total or direct bilirubin ≤ 1.5 x upper limit of normal (ULN) for age; and
    • SGPT (ALT) ≤ 135 U/L (3x ULN). For the purpose of this study, the ULN for SGPT is 45 U/L.
  • Central Nervous System Function Defined As:
    • Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled.
    • Patients must not be in status epilepticus, a coma or on assisted ventilation at the time of study enrollment.
  • Patients must have receptive and expressive language skills in English, French, or Spanish to complete the QoL and Neurocognitive assessments. If a patient meets these criteria but the parent/guardian speaks a language other than English, French, or Spanish, the patient may still be enrolled and tested, and the parent-report measures should be omitted.


Exclusion Criteria:

  • Patients with metastatic disease by either MRI evaluation (brain and spine) or lumbar CSF cytology are not eligible. Patients who are unable to undergo a lumbar puncture for assessment of CSF cytology are ineligible.
  • Patients must not have received any prior radiation therapy or chemotherapy (tumor-directed therapy) other than surgical intervention and/or corticosteroids.
  • Female patients who are pregnant are ineligible due to risks of fetal and teratogenic adverse events as seen in animal/human studies.
  • Lactating females are not eligible unless they have agreed not to breastfeed their infants.
  • Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained.
  • Sexually active patients of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method for the duration of their study participation.
  • Patients with a history of moderate to profound intellectual disability (i.e., IQ < 55) are not eligible for enrollment.
    • PLEASE NOTE: Children with a prior history of attention deficit hyperactivity disorder (ADHD) or a specific learning disability (e.g., dyslexia) are eligible for this study.
  • All patients and/or their parents or legal guardians must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines.
  • All institutional, FDA, and NCI requirements for human studies must be met.

 

 

Drug, Radiation, Administration of antineoplastic agent, Combined chemotherapy and radiation therapy, Whole brain radiation therapy
Brain tumor, Cancer, Embryonal tumor, Medulloblastoma, Pediatric brain tumor
1,2-Diaminocyclohexaneplatinum II citrate, Cancer treatment, Chemotherapy, Classic medulloblastoma, Cyclophosphamide, Lomustine, Medical Oncology, Nervous system, Radiation therapy, Vincristine, cisplatin, cyclophosphamide, lomustine, vincristine
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MC1734 Window Trial of Abemaciclib for Surgically Resectable, Chemotherapy-Resistant, Triple Negative Breast Cancer (a BEAUTY Study*) (BEAUTY-2)

A Study to Evaluate Abemaciclib for Surgically Resectable, Chemotherapy-Resistant, Triple Negative Breast Cancer

Matthew Goetz
Female
18 years and over
Phase 2
This study is NOT accepting healthy volunteers
0000-100372-P01-RST
17-010660
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Inclusion Criteria
•Pre-Registration :

  • Women of age  ≥ 18 years old.
  • Clinical T1-3, N0-3 breast cancer at diagnosis (prior to the start of 4.1.2neoadjuvant chemotherapy) by AJCC staging version 8.
    Note: Benign breast disease, lobular carcinoma in situ (LCIS) or ductal carcinoma in situ (DCIS) in the contralateral breast is allowed.
    Note: Contralateral invasive breast cancer is allowed if disease is of clinically lower stage and the higher stage lesion will be the study lesion for all biopsies and tissue samples.
  • Histological confirmation of triple negative invasive breast cancer 4.1.3(defined as ER≤10%, PR≤10% and HER2 not amplified by ISH or IHC 0/1) at diagnosis.
  • Neoadjuvant chemotherapy (NAC) with one of the following regimens 4.1.4that was not discontinued early due to intolerability with less than 50% of planned treatment given due to disease progression or patient request:
    • Paclitaxel or docetaxel followed by one of the following: the combination of doxorubicin and cyclophosphamide (AC); the combination of epirubicin and cyclophosphamide (EC) or the combination of 5-fluorouracil, epirubicin and cyclophosphamide (FEC) Note: Carboplatin may be added to these regimens
    • AC or EC or FEC followed by docetaxel or paclitaxel
      • Note: Carboplatin may be added to these regimens
    • Docetaxel in combination with doxorubicin and cyclophosphamide (TAC)
  • Residual lesion/enhancement seen in the breast on breast imaging performed after completion of NAC.
  • Able to swallow oral medication.
  • Willing to undergo biopsy for research.
  • Willing to provide tissue and blood samples for correlative research purposes.
  • Willing to stop use of strong and moderate inducers and/or strong inhibitors of cytochrome P450 3A ≤ 7 days prior to registration.
  • Provide written informed consent.

Exclusion Criteria
•Pre-Registration:

  • History of deep venous thrombosis (DVT) or pulmonary embolisms (PE) ≤ 12 months prior to preregistration; OR
  • Active DVT and/or PE requiring anti-coagulant therapy.
    • NOTE: Patients who are on anti-coagulant therapy for maintenance are eligible as long as the DVT and/or PE was > 12 months prior to enrollment and there is no evidence for active thrombosis (either DVT or PE).
      • NOTE: Patients on anticoagulation are eligible; however peri-biopsy and peri-surgical management of anticoagulation is per the institutional standard of care.
  • Prior treatment with CDK 4/6 inhibitors (e.g., palbociclib, ribociclib, abemaciclib, etc.)
  • Prior treatment with immunotherapy or radiation for this breast cancer.
  • Prior incisional or excisional breast biopsy for this cancer.
  • Any contraindications to pre-registration biopsy (such as bleeding diatheses, etc.).
  • Receiving any 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 another specific treatment for prior malignancy.
  • Biopsy proven Stage IV breast cancer.
  • Serious pre-existing medical conditions that would preclude participation in this study (for example, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment [e.g., estimated creatinine clearance <30ml/min], history of major surgical resection involving the stomach or small bowel, or preexisting Crohn’s disease or ulcerative colitis or a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea).
  • History of any of the following conditions:
    • Syncope of cardiovascular etiology
    • Ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation)
    • Sudden cardiac arrest
      • NOTE: Patients on anticoagulation are eligible; however peri-biopsy and peri-surgical management of anticoagulation is per the institutional standard of care.

Inclusion Criteria
•Registration:

  • Registration must occur ≤ 56 days after last dose of NAC.
  • ECOG Performance Status (PS) 0, 1, or 2.
  • The following laboratory values obtained after completion of NAC but ≤ 14 days prior to registration:
    • Absolute neutrophil count (ANC) ≥ 1500/mm^3;
    • Platelets (PLT) ≥100,000/mm^3;
    • Hemoglobin (HgB) ≥ 8.0g/dL;
    • Total bilirubin ≤ 1.5 x ULN;
    • Aspartate transaminase (AST)(SGOT) ≤ 3 x ULN;
    • Alanine aminotransferase (ALT)(SGPT) ≤ 3 x ULN;
    • Serum creatinine ≤1.5 x ULN.
  • Negative pregnancy test done ≤ 7 days prior to registration, for persons of childbearing potential only.

Exclusion Criteria
•Registration:

  • 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.
  • Failure to recover to Grade 1 or lower from effects of neoadjuvant chemotherapy.
    • Exceptions: Residual alopecia and Grade 2 peripheral neuropathy are allowed.
  • Concurrent use of strong and moderate inducers and/or strong inhibitors of cytochrome P450 3A ≤ 7 days prior to registration.
  • Known infections as follows (NOTE: Screening is not required for enrollment):
    • Active systemic  bacterial infection requiring intravenous antibiotics;
    • Active fungal infection (requiring intravenous or oral antifungal treatment);
    • Detectable viral infections (e.g. known HIV, known active hepatitis B or C).
Drug, Administration of antineoplastic agent, Drug therapy finding, Pre-operative chemotherapy
Breast cancer, Cancer, Triple-negative breast cancer
Cancer treatment, Chemotherapy, Chemotherapy for breast cancer, Medical Oncology, Triple-negative breast cancer, abemaciclib, Abemaciclib [USAN:INN], Breast cancer surgery, Targeted drug therapy, Abemaciclib
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Phase II Study of Ibrutinib in Combination With Ixazomib in Patients With Waldenstrom Macroglobulinemia

Ibrutinib and Ixazomib Citrate in Treating Participants With Relapsed or Refractory Waldenstrom Macroglobulinemia

Stephen Ansell
All
18 years and over
Phase 2
This study is NOT accepting healthy volunteers
0000-100381-P01-RST
18-000580
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Inclusion Criteria:

  • Age ≥ 18 years of age.
  • Histological confirmation of WM. Patients may have newly diagnosed, relapsed, or refractory disease.
    • Definition: Newly diagnosed; Patients previously untreated for WM, Relapse; patients who have received prior treatment for WM and now have disease recurrence. Refractory; patients who have received anti-WM therapy and are noted to have progressive disease while on therapy, or those patients who demonstrated disease progression within 6 months of the last anti-WM treatment).
      • NOTE: Ibrutinib naïve patients are allowed. If previously treated with ibrutinib, subject must have reached a response of at least SD and cannot have progressed while on ibrutinib. If subject stopped taking ibrutinib for reasons other than progression, they cannot have progressed for at least 6 months post last dose of ibrutinib.
  • Presence of measurable disease as defined by: presence of immunoglobulin M (IgM) paraprotein, measurable lymphadenopathy on imaging studies and/or physical exam, and/or bone marrow infiltration > 10%.
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1, or 2.
  • Obtained ≤ 14 days prior to registration:
    • Absolute neutrophil count (ANC) ≥ 1000/mm³;
    • Platelet count ≥ 75,000/mm³;
      • NOTE: platelet transfusions in order to help patients meet eligibility criteria are not allowed.
    • Hemoglobin > 9.0 g/dL;
    • Total bilirubin ≤1.5 upper limit of normal (ULN) unless due to Gilbert's syndrome, in which case the direct bilirubin must be ≤ 1.5  x ULN;
    • Aspartate transaminase (AST) and alanine aminotransferase (ALT) ≤ 3  x ULN;
    • Calculated creatinine clearance must be ≥ 30 ml/min using the Cockcroft Gault formula.
  • Negative pregnancy test done at screening and  ≤ 3 days (72 hours) prior to registration, for women of childbearing potential.
  • Provide written informed consent.
  • Willingness to provide mandatory blood specimens and bone marrow specimens for correlative research.
  • Willingness to return to enrolling institution for follow-up.


Exclusion Criteria:

  • Failure to have fully recovered (i.e., ≤ Grade 1 toxicity) from the reversible effects of prior treatment for WM.
  • Major surgical procedure (including open biopsy, excluding central line IV and portacath placement) within ≤ 14 days prior to initiating study treatment, or anticipation of the need for major surgery during the course of the study treatment.
  • Radiotherapy ≤ 14 days prior to registration. If the involved field is small, 7 days will be considered a sufficient interval between treatment and administration of the Ixazomib.
  • Systemic treatment, ≤ 14 days before registration, with strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or St. John’s wort.
  • Systemic anti-cancer therapy or participation in other clinical trials, including those with other investigational agents not included in this trial, ≤ 28 days of registration and throughout the duration of active treatment in this trial.
  • Patients that have previously been treated with ixazomib, or participated in a study with ixazomib whether treated with ixazomib or not.
  • Prior bortezomib treatment is allowed as per:
    • Patients with prior exposure to bortezomib will be allowed if they do not have disease refractory to bortezomib).
  • Central nervous system involvement (Bing-Neel syndrome).
  • Infection requiring systemic antibiotic therapy or other serious infection ≤ 7 days prior to registration.
  • a Evidence of current uncontrolled cardiovascular conditions,  including  uncontrolled hypertension, serious cardiac arrhythmia requiring medication (other than adequately rate-controlled atrial fibrillation), symptomatic congestive heart failure, unstable angina, stroke/TIA within the past 6 months or myocardial infarction within the past 6 months.
  • Known allergy to any of the study medications, their analogues, or excipients in  the various formulations of any agent.
  • Known GI disease or GI procedure that could interfere with the oral absorption or tolerance of ixazomib or ibrutinib, including difficulty swallowing.
  • History of any other prior malignancy.
    • NOTE: Exception to this are adequately treated non-melanoma skin cancers, any in situ 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 at least two years prior to study enrollment.
  • Patient has ≥ Grade 2 peripheral neuropathy or Grade 1 peripheral neuropathy  with pain on clinical examination during the screening period.
  • 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;
    • Nursing women;
    • Men or women of child bearing potential (WCBP) who are unwilling to employ effective contraception. Effective contraception would be defined as utilizing 2 simultaneous methods of contraception from the time of signing consent through 90 days after the last dose of the study drugs unless they agree to participate in true abstinence when this is in line with the preferred and usual lifestyle of the subject. [WCBP: A female who is sexually mature and who: (1) has not undergone a hysterectomy or bilateral oophorectomy; or (2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)].
  • Evidence of any other serious medical condition (such as psychiatric illness, infectious diseases, physical or laboratory findings) that may interfere with the planned treatment, affect compliance or place the patient at high risk from treatment-related complications or potentially interfere with the completion of  the treatment as per the protocol.
  • Ongoing, active hepatitis B or C virus infection, or known human immunodeficiency virus (HIV) positive.
  • Liver disease with Child-Pugh class B or C liver dysfunction.
  • Current treatment with a combination of ibrutinib and strong CYP3A inhibitors.

 

Drug, Other
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A Phase II Randomized Study: Outcomes After Secondary Cytoreductive Surgery With or Without Carboplatin Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Followed by Systemic Combination Chemotherapy for Recurrent Platinum-Sensitive Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

Outcomes After Secondary Cytoreductive Surgery With or Without Carboplatin Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Followed by Systemic Combination Chemotherapy for Recurrent Platinum-Sensitive Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

Carrie Langstraat
Female
21 years and over
Phase 2
This study is NOT accepting healthy volunteers
0000-100389-P01-RST
15-003334
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Inclusion Criteria:

  • Age > 21 years old.
  • Patients with histologic diagnosis of epithelial ovarian carcinoma, primary peritoneal carcinoma, or fallopian tube carcinoma that has recurred >6 months since platinum-based chemotherapy (first recurrence) and who are scheduled for secondary surgical evaluation/cytoreduction.
  • Histologic epithelial cell types include serous, endometrioid, clear cell, or undifferentiated carcinomas, transitional cell carcinoma, mixed epithelial carcinoma, malignant Brenner‟s tumor, or adenocarcinoma N.O.S.
  • Karnofsky Performance Status (KPS) of ≥ 70%.
  • Disease-free interval < 30 months.
  • No prior chemotherapy in the recurrent setting. Prior hormonal therapy is permitted. Concomitant anti-neoplastic anti-hormonal therapy (including tamoxifen, aromatase inhibitors etc.) is not allowed for patients participating in study treatment. Low-dose (physiologic) estrogen hormone-replacement therapy (HRT) may be given.
  • Patients receiving maintenance biologic therapy are eligible, provided their recurrence is documented more than 6 months from completion of primary cytotoxic chemotherapy (includes maintenance chemotherapy) and a minimum of 3 weeks has elapsed since their last infusion of biologic therapy at the start of protocol intervention, day 1.
  • Patients must be, after evaluation by the investigator, appropriate candidates for the administration of 5 to 6 cycles of standard platinum-based combination chemotherapy (carboplatin and paclitaxel, carboplatin and liposomal doxorubicin, or carboplatin and gemcitabine) following CRS with or without HIPEC.

Physical and Laboratory Test Findings

  • Bone marrow function:
    • Hemoglobin ≥ 8.5 g/dL;
    • Absolute neutrophil count (ANC) ≥ 1,000/mm3;
    • Platelets ≥ 100,000/mm3.
  • Renal function:
    • Creatinine ≤ 1.5mg/dl.
  • Hepatic function:
    • Bilirubin ≤ 1.5 times ULN;
    • ALT ≤ 3 times the ULN;
    • AST ≤ 3 times the ULN.
  • Neurologic function:
    • Peripheral neuropathy ≤ CTC AE grade 2.
  • Blood coagulation parameters:
    • PT with an INR of ≤ 1.5 and a PTT ≤ 1.5 times the ULN. For patients on full-dose oral anti-coagulation (such as warfarin or rivaroxaban), in-range INR (usually between 2 and 3) and a PTT <1.2 times the ULN.
  • Patients of childbearing potential must have a negative serum pregnancy test within 2 weeks prior to CRS and must be practicing an effective form of contraception during the study period.

Inclusion Criteria for Eligibility post-surgery

  • Patients will be consented prior to the surgical evaluation/cytoreductive surgery. Patients must have less than or equal to 0.5 cm residual disease at the completion of the secondary surgery to be eligible for the study.


Exclusion Criteria:

  • Tumors of low malignant potential (borderline carcinomas).
  • Subjects who have received prior radiotherapy to any portion of the abdominal cavity or pelvis are excluded.
  • Patients with a history of primary endometrial cancer are excluded unless the following conditions are met:
    • Stage not greater than IA;
    • Not a poorly differentiated subtype (including papillary serous, clear cell or other FIGO grade 3 lesions).
  • With the exception of non-melanoma skin cancer and other specific malignancies as noted above, subjects with other invasive malignancies, who had any evidence of the other cancer present within the last 1 year or whose previous cancer treatment contraindicates this protocol therapy, are excluded.
  • Subjects with known active acute hepatitis.
  • Subjects with active infection that requires parenteral antibiotics.
  • Active coronary artery disease (defined as unstable angina or a positive cardiac stress test).
  • Patients with a history of coronary artery disease may be included if they have had a normal stress test within 30 days of enrollment.
  • Uncontrolled hypertension defined as > 140/90 and not cleared for surgery at the time of consent.
  • New York Heart Association (NYHA) Class II or higher congestive heart failure.
  • History of cerebrovascular disease.
  • Immune deficiency: Clinically significant primary or acquired immune deficiency (i.e., AIDS or on immunosuppressive medication after organ transplant)
  • Patients with other concurrent severe medical problems unrelated to the malignancy that would significantly limit full compliance with the study or places them at an unacceptable risk for participation in the study.
  • Patients with known carboplatin or cisplatin allergy.
  • Life expectancy < 12 weeks.

Exclusion Criteria for Eligibility post-surgery

  • Evidence of extensive intraperitoneal adhesions at the time of surgery, as determined by the operating surgeon which prohibits intraperitoneal therapy.

 

Drug, Procedure/Surgery, Drug therapy
Cancer, Fallopian tube cancer, Ovarian cancer, Peritoneal cancer, Recurrent cancer
Cancer treatment, Carboplatin, Carcinoma of fallopian tube, Chemotherapy, HIPEC, Malignant epithelial tumor of ovary, Malignant tumor of peritoneum, Medical Oncology, Reproductive system, carboplatin
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WISP (Women Choosing Surgical Prevention) (WISP)

The Women Choosing Surgical Prevention (WISP) Trial

Jamie Bakkum-Gamez
Female
30 years to 50 years old
This study is NOT accepting healthy volunteers
0000-100392-P01-RST
16-003627
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Inclusion Criteria:

  1. Women must be >/= 30 and </= 50 years of age.
  2. Premenopausal women with a documented deleterious mutation in one of the following ovarian cancer genes: BRCA1, BRCA2, BRIP1, PALB2, RAD51C, RAD51D, BARD1, MSH2, MSH6, MLH1, PMS2, or EPCAM. (Please note: Menopause is defined as >/= 12 months of amenorrhea. However, for those patients with >/= 12 months of amenorrhea who may be pre-menopausal, levels of FSH, LH, and estradiol in the pre-menopausal range will be acceptable).
  3. Willing to undergo two surgical procedures (if participant chooses the ISDO arm)
  4. Presence of at least 1 fallopian tube and 1 ovary. (Please note: Prior unilateral salpingectomy is allowed; prior bilateral salpingectomy is not allowed)
  5. Patients who have undergone a prior tubal ligation will be eligible.
  6. Participants may have a personal history of non-ovarian malignancy, but must: a) be without evidence of disease at enrollment b) remain premenopausal c) have completed treatment (including surgery, chemotherapy, radiotherapy or hormonal therapy) >3 months prior to enrollment (other than non-melanoma skin cancer)
  7. Willingness to return to the enrolling site for the study surgical procedures, including pre-operative and post-operative care. (Patients in the ISDO arm must be willing to return to the enrolling site for yearly ovarian cancer assessment)
  8. Patients must understand that they will be permanently sterilized


Exclusion Criteria:

  1. Women with a personal history of ovarian, fallopian tube, or primary peritoneal cancer
  2. Current treatment with Tamoxifen or Aromatase Inhibitors
  3. Medical comorbidities making surgery unsafe as determined by the patient's surgeon
  4. Women who are pregnant or post-partum (within 3 months of delivery). -Patients are deemed not pregnant by virtue of urine pregnancy test (UPT), transvaginal ultrasound, beta HCG, or best judgement of the investigator. Pregnancy testing is not required per protocol to determine study eligibility -Women who become pregnant on the ISDO arm via reproductive technology can remain on study. However, data collection will be suspended during pregnancy and 3 months post-partum
  5. Women with elevated levels of CA125 (>50) or transvaginal ultrasound suggesting cancer, unless findings are consistent with endometriosis. CA125 and transvaginal ultrasounds must be the most recent, but no older than 1 year from the date of enrollment.
  6. Inability to provide informed consent.
  7. Inability to read or speak English.
Breast cancer, Cancer, Female sexual dysfunction, Ovarian cancer
Abnormal female sexual function, At risk of breast cancer, Medical Oncology, Oophorectomy, Ovarian cancer genetic marker of susceptibility positive, Reproductive system
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A 36 Month Multi-center, Open Label, Randomized, Comparator Study to Evaluate the Efficacy and Safety of Everolimus Immunosuppression Treatment in Liver Transplantation for Hepatocellular Carcinoma Exceeding Milan Criteria

Safety and Efficacy of Everolimus Treatment in Liver Transplantation for Liver Cancer

Timucin Taner
All
18 years and over
Phase 4
This study is NOT accepting healthy volunteers
0000-100393-P01-RST
14-002782
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Inclusion Criteria:

Screening

Inclusion Criteria:

  • Have a diagnosis of hepatocellular carcinoma (HCC) and high risk for HCC recurrence
  • Able to provide written informed consent
  • Male and female patients of any race, 18 years or older
  • De novo recipients of a primary orthotopic liver transplant from a deceased or living donor
  • Patients willing to comply with study requirements
  • Women of child-bearing potential (WOCBP) must agree to use an effective method(s) of contraception during treatment and during the post treatment follow-up period

Screening


Exclusion Criteria:

  • Past or present malignancy within the last 5 years.
  • Severe infection considered by the local site investigator to be unsafe for study participation.
  • Use of other investigational drugs at the time of screening or within the last 30 days.
  • Patients scheduled for a combined transplant (such as liver-kidney), or having a previous solid organ, bone marrow, or autologous islet cell transplant.
  • Recipients of donor/recipient ABO incompatible grafts.
  • Recipients of organs from human immunodeficiency virus (HIV) or HBsAg positive donors.
  • Macrovascular tumor invasion.
  • Proteinuria greater than 2 grams.
  • Conditions which can result in impaired absorption, distribution, metabolism or excretion of the study treatment.
  • Patients with non-infectious pneumonitis.
  • Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test.
  • Women of child-bearing potential (WOCBP) not practicing an effective method(s) of contraception.
  • Patients who receive sirolimus (Rapamune®) as part of their transplant immunosuppression regimen

Randomization Screening Inclusion Criteria :

- For patients with a history of any hepatic vessel thrombosis, occlusion, stent placement, or major revision of liver vessels, must have a Doppler ultrasound prior to randomization to rule out any hepatic vessel complication, including hepatic arterial thrombosis (HAT).

Randomization


Exclusion Criteria:

  • Patients who receive sirolimus (Rapamune) any time prior to randomization will be withdrawn from the study.
  • Patients who develop clinically significant systemic infections requiring active use of IV antibiotics any time prior to randomization.
  • Wound healing problem, per Investigator's assessment, that would make the patient ineligible for study randomization
  • Confirmed presence of a thrombosis in a major hepatic artery(s), major hepatic vein(s), portal vein or inferior vena cava via Doppler ultrasound or other imaging obtained prior to randomization.
  • Proteinuria greater than 2 grams
  • Consideration by the investigator, for any reason, that the subject is an unsuitable candidate to receive everolimus or be randomized into the study.
Drug, Drug therapy, Transplantation of liver
Cancer, Liver cancer, Liver hemangioma
Acute cellular graft rejection, Digestive system, Hepatic artery thrombosis, Hernia repair, Hyperlipidemia, Hypertension associated with transplantation, Liver cell carcinoma, Liver transplant, Medical Oncology, Myfortic, Neoplasm of liver, Renal function, Viral hepatitis C, everolimus, mycophenolate mofetil, tacrolimus
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A Phase 1 Study of the Highly-selective RET Inhibitor, BLU-667, in Patients with Thyroid Cancer, Non-Small Cell Lung Cancer (NSCLC) and Other Advanced Solid Tumors

Study of BLU-667 in Patients with Thyroid Cancer, Non-Small Cell Lung Cancer (NSCLC) and Other Advanced Solid Tumors

Aaron Mansfield
All
18 years and over
Phase 1/2
This study is NOT accepting healthy volunteers
0000-100394-P01-RST
18-005844
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Inclusion Criteria:

  • Patient is ≥ 18 years of age.
  • Diagnosis during dose escalation (Part 1) – Pathologically documented, definitively diagnosed non-resectable advanced solid tumor.
    • All patients treated at doses > 120 mg per day must have MTC, or a RET-altered solid tumor per local assessment of tumor tissue and/or blood;
    • Part 1 enrichment patients must have MTC or a RET-altered solid tumor per local assessment of tumor tissue and/or blood.
  • Diagnosis during dose expansion (Part 2) – All patients (with the exception of patients with MTC enroled in Groups 3, 4 and 9) must have an oncogenic RET fusion or mutation (excluding synonymous, frameshift, and nonsense mutations) solid tumor, as determined by local or central testing of tumor or circulating tumor nucleic acid in blood; as detailed below:
    • Group 1 – patients must have pathologically documented, definitively diagnosed locally advanced or metastatic NSCLC with a RET fusion previously treated with a platinum-based chemotherapy.
    • Group 2 – patients must have pathologically documented, definitively diagnosed locally advanced or metastatic NSCLC with a RET fusion not previously treated with a platinum-based chemotherapy.
    • Group 3 – patients must have pathologically documented, definitively diagnosed advanced MTC that has progressed within 14 months prior to the Screening Visit and was previously treated with cabozantinib and/or vandetanib.
    • Group 4 – patients must have pathologically documented, definitively diagnosed advanced MTC that has progressed within 14 months prior to the Screening Visit and was not previously treated with cabozantinib or vandetanib.
    • Group 5 – patients must have a pathologically documented, definitively diagnosed advanced solid tumor with an oncogenic RET fusion, have previously received SOC appropriate for their tumor type (unless there is no accepted standard therapy for the tumor type or the Investigator has determined that treatment with standard therapy is not appropriate) and must not eligible for any of the other groups.
    • Group 6 – patients must have a pathologically documented, definitively diagnosed advanced solid tumor with an oncogenic RET fusion or mutation, previously treated with a selective TKI that inhibits RET, such as selpercatinib.
    • Group 7 – patients must have a pathologically documented, definitively diagnosed advanced solid tumor with an oncogenic RET mutation previously treated with SOC appropriate for the tumor type and not eligible for any of the other groups.
    • Group 8 – patients must have pathologically documented, definitively diagnosed locally advanced or metastatic NSCLC with a RET fusion that was previously treated with a platinum-based chemotherapy (China only).
    • Group 9 – patients must have pathologically documented, definitively diagnosed advanced MTC that has progressed within 14 months prior to the Screening Visit and was not previously treated with systemic therapy (except prior cytotoxic chemotherapy is allowed) for advanced or metastatic disease (China only).
  • Patient must have non-resectable disease that has progressed following standard therapy or has not adequately responded to standard therapy, or the patient must be intolerant to, or the Investigator has determined that treatment with standard therapy is not appropriate, or there must be no accepted standard therapy for their disease.
  • Dose expansion (Part 2) patients in all groups (ecept Group 7) must have measurable disease per RECIST v1.1 (or RANO, if appropriate for tumor type).
  • Patient agrees to provide tumor tissue (archived, if available or a fresh biopsy) for RET status confirmation and is willing to consider an on-treatment tumor biopsy, if considered safe and medically feasible by the treating Investigator. For Part 2, Group 6, patients are required to undergo a pretreatment biopsy to define baseline RET status in tumor tissue.
  • Patient has Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1.
  • Patient provides informed consent to participate in the study.


Exclusion Criteria:

  • Patient’s cancer has a known primary driver alteration other than RET. For example, NSCLC with a targetable mutation in EGFR, ALK, ROS1, or BRAF; colorectal with an oncogenic KRAS, NRAS, or BRAF mutation. Investigators should discuss enrollment with Sponsor regarding co-mutations.
  • Patient has any of the following within 14 days prior to the first dose of study drug:
    • Platelet count < 75 × 109/L;
    • Absolute neutrophil count (ANC) < 1.0 × 109/L;
    • Hemoglobin < 9.0 g/dL (red blood cell transfusion and erythropoietin may be used to reach at least 9.0 g/dL, but must have been administered at least 2 weeks prior to the first dose of study drug;
    • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 × the upper limit of normal (ULN) if no hepatic metastases are present; > 5 × ULN if hepatic metastases are present;
    • Total bilirubin > 1.5 × ULN; > 3 × ULN with direct bilirubin > 1.5 × ULN in presence of Gilbert’s disease;
    • Estimated (Cockroft-Gault formula) or measured creatinine clearance < 40 mL/min;
    • Total serum phosphorous > 5.5 mg/dL.
  • Patient has a QTcF > 470 msec. Patient has a history of prolonged QT syndrome or Torsades de pointes. Patient has a familial history of prolonged QT syndrome.
  • Patient has clinically significant, uncontrolled, cardiovascular disease including congestive heart failure Grade III or IV according to the New York Heart Association (NYHA) classification; myocardial infarction or unstable angina within the previous 6 months, uncontrolled hypertension, or clinically significant, uncontrolled arrhythmias, including bradyarrhythmias that may cause QT prolongation (e.g., Type II second degree heart block or third degree heart block).
  • Patient has central nervous system (CNS) metastases or a primary CNS tumor that is associated with progressive neurological symptoms or requires increasing doses of corticosteroids to control the CNS disease. If a patient requires corticosteroids for management of CNS disease, the dose must have been stable for the 2 weeks preceding C1D1.
  • Presence of clinically symptomatic interstitial lung disease or interstitial pneumonitis, including radiation pneumonitis (i.e., affecting activities of daily living or requiring therapeutic intervention).
  • Patient received the following anticancer therapy:
    • Any systemic anticancer therapy (except for immunotherapy or other antibody therapies) and all forms of radiotherapy, within 14 days or 5 half-lives prior to the first dose of study drug. Pralsetinib may be started within these washout periods if considered by the Investigator to be safe and within the best interest of the patient, with prior Sponsor approval;
    • Any immunotherapy or other antibody therapy within 28 days prior to the first dose of study drug (immune related toxicities must have resolved to < Grade 2 prior to starting Pralsetinib).
  • Dose expansion patients in Groups 1-5 and 7 (Part 2): patient has previously received treatment with a selective RET inhibitor such as selpercatinib.
  • Patient received neutrophil growth factor support within 14 days of the first dose of study drug.
  • Patient requires treatment with a prohibited medication or herbal remedy that cannot be discontinued at least 2 weeks before the start of study drug administration. Pralsetinib may be started within 14 days or 5 half-lives of prior therapy if considered by the Investigator to be safe and within the best interest of the patient, with prior Sponsor approval.
  • Patient has had a major surgical procedure within 14 days of the first dose of study drug (procedures such as central venous catheter placement, tumor needle biopsy, and feeding tube placement are not considered major surgical procedures).
  • Patient has a history of another primary malignancy that has been diagnosed or required therapy (except maintenance anti-hormonal therapy) within the past year. The following prior malignancies are not exclusionary: completely resected basal cell and squamous cell skin cancer, curatively treated localized prostate cancer, curatively treated localized thyroid cancer, and completely resected carcinoma in situ of any site.
  • Patient is unwilling or unable to comply with scheduled visits, drug administration plan, laboratory tests, or other study procedures and study restrictions.
  • Women who are unwilling, if not postmenopausal or surgically sterile, to abstain from sexual intercourse or employ highly effective contraception during the study drug administration period and for at least 30 days after the last dose of study drug. Men who are unwilling, if not surgically sterile, to abstain from sexual intercourse or employ highly effective contraception during the study drug administration period and for at least 90 days after the last dose of study drug.
  • Pregnant females, as documented by a serum beta human chorionic gonadotropin (β-hCG) pregnancy test consistent with pregnancy, obtained within 7 days prior to the first dose of study drug. Females with β-hCG values that are within the range for pregnancy but are not pregnant (false-positives) may be enrolled with written consent of the Sponsor, after pregnancy has been ruled out. Females of non-childbearing potential (postmenopausal for more than 1 year; bilateral tubal ligation; bilateral oophorectomy; hysterectomy) do not require a serum β-hCG test.
  • If female, patient is breastfeeding.
  • Patient has prior or ongoing clinically significant illness, medical condition, surgical history, physical finding, or laboratory abnormality that, in the Investigator’s or Sponsor's opinion, could affect the safety of the patient; alter the absorption, distribution, metabolism, or excretion of the study drug; or impair the assessment of study results.

 

Drug, Administration of antineoplastic agent, Drug therapy
Cancer, Lung cancer, Medullary thyroid carcinoma, Non-small cell lung cancer, Thyroid cancer
Cancer treatment, Endocrine system, Medical Oncology, Medullary thyroid carcinoma, Non-small cell lung cancer, Pralsetinib, Respiratory system, Solid tumor configuration
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A Phase Ib Trial of CB-839 in Combination With Radiation Therapy and Temozolomide in Patients With IDH-Mutated Diffuse Astrocytoma and Anaplastic Astrocytoma

A Study to Evaluate CB-839 With Radiation Therapy and Temozolomide in Treating Participants With IDH-Mutated Diffuse Astrocytoma or Anaplastic Astrocytoma

Sani Kizilbash
All
16 years and over
Phase 1
This study is NOT accepting healthy volunteers
0000-100399-P01-RST
18-011454
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Inclusion Criteria:
 

  • Patients must have histopathologic or molecular confirmation of either IDH-mutant DA or IDH-mutant AA. Acceptable IDH mutations for study eligibility include any IDH1 mutation at codon 132 or any IDH2 mutation at codon 172. 
  • Age ≥ 16 years. The intended neurocognitive tests have not been validated in children below the age of 16. 
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%). 
  • Hemoglobin > 9.0 g/dL. 
  • Leukocytes >= 3.0 x 10^9/L.
  • Absolute neutrophil count >= 1.5 x 10^9/L.
  • Platelets >= 100 x 10^9/L.
  • International normalized ratio (INR) =< 1.5 x upper limit of normal (ULN).
  • Partial thromboplastin time (PTT) or activated partial thromboplastin time (APTT) =< 1.5 x ULN. 
  • Patients on a stable dose of anti-coagulation therapy will be allowed to participate if they have no signs of bleeding or clotting and the INR/PT and PTT/aPTT results are compatible with an acceptable risk-benefit ratio as per the investigator's discretion.
  • Total bilirubin =< 1.5 x institutional ULN and < 3 mg/dL for patients with Gilbert's disease.
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) & alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x institutional ULN. 
  • Creatinine =< 1.5 x institutional ULN or creatinine clearance >= 60 mL/minute.
  • If there is history of human immunodeficiency virus (HIV) infection, patients must be on effective antiretroviral therapy and HIV viral load must be undetectable within 6 months of study enrollment. 
  • If there is history of chronic hepatitis B virus (HBV) infection, patients must have either been treated or are on suppressive therapy (as indicated), and HBV viral load must be undetectable.
  • If there is history of hepatitis C virus (HCV) infection, patients must have been treated and HCV viral load must be undetectable. 
  • Patient must have measurable disease by RANO criteria (dose expansion cohort only). 
  • Patient must be at least 7 days beyond stereotactic biopsy and/or at least 14 days beyond open craniotomy.
  • Patients must have been on a stable or decreasing dose of corticosteroids over the last 7 days.
  • Patients must have been on a stable or decreasing dose of antiepileptic therapy over the last 14 days. 
  • Females of childbearing potential must have a negative pregnancy test (=<14 days) prior to start of trial treatment. The effects of CB-839 HCl on the developing human fetus are unknown. For this reason and because alkylating agents as well as TMZ 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. 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 4 months after completion of CB-839 HCl administration.
  • Ability to understand and the willingness to sign a written informed consent document.


Exclusion Criteria:

  • Patients must not have received prior chemotherapy to treat the glioma. 
  • Patients who are receiving any other investigational agents. 
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to CB-839 HCl or TMZ. 
  • Patient must not have received prior radiation therapy to the brain. Prior radiation therapy to the head and neck is also excluded if radiation fields overlap. 
  • No prior use of Gliadel wafers. 
  • Patient must have no evidence of either infratentorial or spinal involvement with tumor. 
  • Patients who are unable to swallow tablets.
  • Patients who are at risk for impaired absorption of oral medication including, but not limited to, refractory vomiting, gastric resection/bypass, and duodenal/jejunal resection. 
  • 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. 
  • Patients with a "currently active" second malignancy other than non-melanoma skin cancers. Patients are not considered to have a "currently active" malignancy if they have completed therapy and are free of disease for more than 3 years. 
  • Pregnant women are excluded from this study because CB-839 HCl is an agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for AEs in nursing infants secondary to treatment of the mother with CB-839 HCl, breastfeeding should be discontinued if the mother is treated with CB-839 HCl. These potential risks may also apply to TMZ.
Drug, Other, Radiation, Administration of antineoplastic agent, Chemotherapy, Drug therapy, Radiation therapy procedure or service
Astrocytoma, Brain tumor, Cancer, Glioma
Anaplastic astrocytoma of central nervous system, Cancer treatment, Chemotherapy, Medical Oncology, Nervous system, Radiation therapy, temozolomide
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EA1151, Tomosynthesis Mammographic Imaging Screening Trial (TMIST)

A Study of 3-D Digital Mammography to Screen Patients for Breast Cancer

Katie Hunt
Female
45 years to 74 years old
Phase 3
This study is NOT accepting healthy volunteers
0000-100404-P01-RST
19-004054
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Inclusion Criteria:
 

  • Patients must be women age 45 or older and under age 75 at the time of study entry.
  • Women of childbearing potential must not be known to be pregnant or lactating.
  • Patients must be scheduled for, or have intent to schedule, a screening mammogram.
  • Patients must be able to tolerate digital breast tomosynthesis and full-field digital mammographic imaging required by protocol, to be performed at an American College of Radiology Imaging Network (ACRIN)-qualified facility.
  • Patients must be willing and able to provide a written informed consent.
  • Patients must not have new symptoms or signs of benign or malignant breast disease (e.g., bloody or clear nipple discharge, breast lump) based on physician physical exam or self breast exam that have not been previously worked up with imaging. Patients with physiologic nipple discharge or breast pain are eligible as long as other criteria are met.
  • Patients must not have had a screening mammogram within the last 11 months prior to date of randomization.
  • Patients must not have previous personal history of breast cancer including ductal carcinoma in situ.
  • Patients must not have breast enhancements (e.g., implants or radiopaque injections).

ANNUAL SCREENING REGIMEN ELIGIBILITY CHECK 

To be eligible for inclusion in the annual screening regimen one of the following three conditions must be met in addition to the eligibility criteria above:

  • Patients are pre-menopausal; or
  • Post-menopausal aged 45-69 with any of the following four risks factors:
    • Dense Breasts (BIRADS density categories c-heterogeneously dense or d-extremely dense), or
    • At least one benign breast biopsy with a diagnosis of Lobular Carcinoma in Situ (LCIS) or atypia of any kind (atypical ductal hyperplasia, atypical lobular hyperplasia, atypical hyperplasia NOS, or intraductal papilloma with atypia), or
    • Family history of breast cancer (first degree relative with breast cancer) or family history of breast cancer is not known, or, participant positive genetic testing for any deleterious genes that indicate an increased risk for breast cancer, or
    • Currently on hormone therapy¹; or
  • Post-menopausal ages 70-74 with either of the following three risk factors:
    • Dense Breasts (BIRADS density categories c-heterogeneously dense or d-extremely dense); or
    • At least one benign breast biopsy with a diagnosis of LCIS or atypia of any kind (atypical ductal hyperplasia, atypical lobular hyperplasia, atypical hyperplasia NOS, or intraductal papilloma with atypia); or
    • Currently on hormone therapy¹.
  • Postmenopausal women are defined as those with their last menstrual period more than 12 months prior to study entry. For the purpose of defining menopausal status for women who have had surgical cessation of their periods, women who no longer have menses due to bilateral oophorectomy with either hysterectomy or endometrial ablation will be considered postmenopausal. Women who no longer have menses due to either hysterectomy or endometrial ablation, and who have at least one ovary will be considered premenopausal until age 52 and postmenopausal thereafter.
  • All other postmenopausal women are eligible for inclusion in the biennial screening regimen.
  • For those women who cannot be assigned to annual or biennial screening at the time of study entry and randomization because they are postmenopausal, have no family history or known deleterious breast cancer mutation, are not on hormone therapy1 AND for whom a prior mammogram interpretation is not available, breast density will be determined by the radiologist’s recording of it at the time of interpretation of the first study screening examination, either DM or TM. For those who are randomized to TM, radiologists will assign BI-RADS density through review of the DM or synthetic 2D portion of the TM examination. Such women cannot be part of the planned stratification by screening frequency and are expected to represent far less than 1% of the TMIST population.
  • ¹ For this study we define hormone therapies as those that increase breast cancer risk, including: estrogen, progesterone, estrogen/progesterone analogs, or hormonal birth control prescribed by a doctor, and include hormones in oral contraceptives, patch, gel, etc. BUT, for this study, Soy use is not considered hormone therapy.
  • Breast density will be determined by prior mammography reports, when available, or by radiologist review of prior imaging.
    • NOTE: If the latter method is used, a signed, dated attestation by the radiologist indicating the resulting determination must be kept as a record and made available for monitoring/auditing.
  • All other risk factors used to determine patient eligibility for annual or biennial screening will be determined by subject self-report.
Diagnostic Test, Procedure/Surgery, Other, Digital breast tomosynthesis, Screening for malignant neoplasm of breast, Screening mammography
Breast cancer, Cancer
3D mammogram, Breast exam, Malignant tumor of breast, Mammogram, Medical Oncology
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MC1831 Therapeutic Targeting of ER Beta in Triple Negative Breast Cancer

Estradiol in Treating Patients With ER Beta Positive, Triple Negative Locally Advanced or Metastatic Breast Cancer

Matthew Goetz
Female
18 years and over
Phase 2
This study is NOT accepting healthy volunteers
0000-100406-P01-RST
18-000734
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Inclusion Criteria:


- PRE-SCREENING CRITERIA (STEP 0): History of locally advanced or metastatic breast
cancer that is ERalpha negative or low (< 1% nuclear staining) and HER2 negative.

- Note: HER2 negative disease per 2018 American Society of Clinical
Oncology/College of American of Pathologists (ASCO/CAP) guidelines, one of the
following must apply:

- 0 or 1+ by immunohistochemistry (IHC) and not amplified by in situ
hybridization (ISH);

- 0 or 1+ by IHC and ISH not done;

- 2+ by IHC and ISH results are: < 6.0 HER2 signals/cell with HER2/CEP17 ratio
< 2.0;

- IHC not done and not amplified by ISH.

- PRE-SCREENING CRITERIA (STEP 0): =< 3 prior chemotherapy regimens for treatment of
metastatic breast cancer.

- Note: Prior use of monoclonal antibodies targeting PD1, PDL1 is allowed (if
administered as monotherapy it is not counted as a chemotherapy regimen).

- PRE-SCREENING CRITERIA (STEP 0): Eastern Cooperative Oncology Group (ECOG) performance
status 0 or 1

- PRE-SCREENING CRITERIA (STEP 0): Willing to submit a biopsy specimen from locally
recurrent or metastatic site (or primary if metastatic site not available) of breast
cancer for ERbeta staining to Mayo Clinic Anatomic Pathology.

- PRE-REGISTRATION CRITERIA (STEP 1): Presence of moderate or strong nuclear ERbeta
staining in > 25% of cells in specimen submitted during Pre-Screening Step.

- PRE-REGISTRATION CRITERIA (STEP 1): For patients who did not have a biopsy or lacking
ERalpha, progesterone receptor (PR), and HER2 results from a locally advanced or
metastatic site performed =< 12 months prior to Pre-Registration: Willing to undergo a
standard of care biopsy of locally recurrent or metastatic breast cancer for ERalpha,
PR, and HER2 as well as additional research cores.

- PRE-REGISTRATION CRITERIA (STEP 1): Measurable or non-measurable disease as defined by
Response Evaluation Criteria in Solid Tumors (RECIST) criteria that will be assessed
using imaging-based evaluations.

- Note: The tumor lesion biopsied during the pre-registration period is not
considered measurable disease nor a target lesion.

- PRE-REGISTRATION CRITERIA (STEP 1): If history of brain metastases must meet the
following criteria:

- Patients with a history of brain metastases are eligible only if they are
asymptomatic and have stable disease for >= 3 months, including < 28 days of
prior to pre-registration.

- Not receiving steroids for brain metastases.

- PRE-REGISTRATION CRITERIA (STEP 1): ECOG performance status 0 or 1.

- PRE-REGISTRATION CRITERIA (STEP 1): =< 3 prior chemotherapy regimens for treatment of
metastatic breast cancer.

- NOTE: Prior use of monoclonal antibodies targeting PD1, PDL1 is allowed.

- PRE-REGISTRATION CRITERIA (STEP 1): Women must be postmenopausal.

- NOTE: Postmenopausal status is verified by:

- Prior bilateral surgical oophorectomy, or

- Age >= 60 years, or

- Age < 60 years with no menses for > 1 year with estradiol levels within
postmenopausal range, according to institutional standard.

- PRE-REGISTRATION CRITERIA (STEP 1): Able to swallow oral medications.

- PRE-REGISTRATION CRITERIA (STEP 1): Willingness to stop use of strong inducers or
inhibitors of CYP3A4 prior to registration.

- NOTE: Use of strong inducers or inhibitors is allowed during pre-registration as
long as patient will complete course prior to registration.

- REGISTRATION CRITERIA (STEP 2): For patents who had a biopsy taken from a metastatic
site =< 12 months prior to Pre-Registration: Confirmation from the local lab that the
tumor from this biopsy was ERalpha negative (< 1% nuclear staining) and HER2 negative

- REGISTRATION CRITERIA (STEP 2): For patients who underwent a pre-registration biopsy:
Histologic confirmation from local lab that tumor is ERalpha negative (< 1% nuclear
staining), and HER2 negative

- REGISTRATION CRITERIA (STEP 2): Hemoglobin >= 8 g/dL (=< 14 days prior to
registration).

- REGISTRATION CRITERIA (STEP 2): Platelet count >= 75,000/mm^3 (=< 14 days prior to
registration).

- REGISTRATION CRITERIA (STEP 2): Creatinine =< 1.5 x upper limit of normal (ULN) (=< 14
days prior to registration).

- REGISTRATION CRITERIA (STEP 2): Total bilirubin =< 1.5 x ULN (=< 14 days prior to
registration).

- REGISTRATION CRITERIA (STEP 2): Aspartate aminotransferase/serum glutamic-oxaloacetic
transaminase (AST/SGOT) =< 2.5 x ULN (=< 14 days prior to registration).

- For patients with liver metastasis =< 5 x ULN.


Exclusion Criteria:


- PRE-REGISTRATION CRITERIA: Uncontrolled intercurrent illness including, but not
limited to:

- Ongoing or active infection.

- Symptomatic congestive heart failure.

- Unstable angina pectoris.

- Uncontrolled symptomatic cardiac arrhythmia.

- Uncontrolled hypertension (defined as blood pressure > 160/90).

- PRE-REGISTRATION CRITERIA: Deep vein thrombosis / pulmonary embolism (DVT/PE) =< 12
months prior to pre-registration.

- Note: Patients who are on anticoagulant therapy for maintenance are eligible as
long as the DVT and/or PE occurred > 6 months prior to pre-registration, and
there is no evidence for active thrombosis (either DVT or PE).

- PRE-REGISTRATION CRITERIA: Stroke =< 6 months prior to pre-registration.

- PRE-REGISTRATION CRITERIA: Two or more episodes of DVT and/or PE =< 5 years prior to
pre-registration.

- PRE-REGISTRATION CRITERIA: Abnormal uterine bleeding =< 6 months prior to
pre-registration

- PRE-REGISTRATION CRITERIA: History of coagulopathy.

- PRE-REGISTRATION CRITERIA: Other active second malignancy other than non-melanoma skin
cancers within 3 years prior to pre-registration.

- NOTE: A second malignancy is not considered active if all treatment for that
malignancy is completed and the patient has been disease-free for >= 3 years
prior to pre-registration.

- REGISTRATION CRITERIA: None of the following therapies are allowed =< 14 days prior to
registration.

- Chemotherapy.

- Immunotherapy.

- Biologic therapy.

- Hormonal therapy.

- Monoclonal antibodies.

- Anti-HER2 or other "targeted" (e.g. mTOR) therapy.

- Note: Any adverse events derived from these therapies must be =< grade 2 prior to
starting study therapy (exceptions for alopecia).

Drug, Administration of antineoplastic agent, Drug therapy, Biologic/Vaccine
Breast cancer, Cancer, Triple-negative breast cancer
Cancer treatment, Medical Oncology, Secondary malignant neoplasm of female breast, Triple-negative breast cancer, Hormone therapy for breast cancer, Targeted drug therapy
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