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Clinical Trial 19112

Cancer Type: Multiple
Interventions:BMS-936558 (Nivolumab); Ipilimumab; Nivolumab; Yervoy (Ipilimumab)

Study Type: Treatment
Phase of Study: Phase I

  • Jonathan Strosberg

Call 813-745-6100
or 1-800-679-0775

Study Title

DART: Dual Anti-CTLA-4 and Anti-PD-1 Blockade in Rare Tumors


This clinical trial studies nivolumab and ipilimumab in treating patients with rare tumors. Monoclonal antibodies, such as nivolumab and ipilimumab, may interfere with the ability of tumor cells to grow and spread.


Primary Objective: a.) To evaluate the RECIST 1.1 overall response rate (ORR) in subsets of patients with advanced rare cancers treated with ipilimumab plus nivolumab combination immunotherapy. Secondary Objectives: a.) To evaluate toxicities in each cohort. b.) To estimate overall survival (OS), progression-free survival (PFS), clinical benefit rate; and to estimate immune-related ORR (irORR), and immune-related PFS (irPFS) by unidimensional immune-related response criteria. c.) To collect specimens for banking for use in future correlative biomarker research studies.

Inclusion Criteria

  • Participants must have histologically confirmed rare cancer and/or cancer of unknown primary, that did not have a match to a molecularly-guided therapy on EAY131 "National Cancer Institute (NCI)-Molecular Analysis for Therapy Choice (MATCH)" protocol or who progressed on molecularly-matched therapy and have no further molecularly-matched treatment recommendations per EAY131, "NCI-MATCH". All baseline assessments must have been completed within 28 days prior to registration.
  • Those who do not qualify for one of the histologic cohorts may be considered for registration in the "Not Otherwise Categorized" Rare Tumors cohort with confirmation of the study chairs via email.
  • Have a rare cancer with unknown primary site: eligible if there is histologic documentation of metastatic malignancy with no discernible primary site identified from histopathologic review, physical exam and associated cross-sectional imaging of the chest, abdomen, and pelvis.
  • Have a diagnostic quality CT scan or MRI, performed within 28 days prior to registration, which demonstrates measurable disease, as defined in RECIST v. 1.1; all disease must be assessed and documented on the S1609 Baseline Tumor Assessment Form.
  • No other prior malignancy allowed, except: Adequately managed stage I or II cancer from which the patient is currently in complete remission; Any other cancer from which the patient has been disease free for 5 years; Adequately managed stage I or II follicular thyroid or prostate cancer is also eligible, wherein patient is not required to be in complete remission.
  • Patients who have received prior anti-CTLA4 or other anti-PD-1/anti-PD-L1 therapy, not both, provided that it is completed >= 4 weeks prior to registration for monoclonal therapy, >= 8 weeks prior to registration if therapy involved immunestimulatory monoclonal antibody (mAb)s, and >= 28 days for all other immunotherapy.
  • Patients with clinically controlled thyroiditis or pituitary disorders on stable replacement therapy are eligible.
  • Patients with brain metastases or primary brain tumors must have completed treatment, surgery or radiation therapy >= 28 days prior to registration and have stable disease at time of registration; metastatic brain parenchymal disease must have been treated and be off steroids for 7 days prior to registration.
  • Zubrod performance status of 0-2.
  • Adequate hepatic, bone marrow, renal, thyroid, and adrenal axis function
  • Females of childbearing potential must have negative serum pregnancy test 14 days prior to registration and agree to use birth control throughout study and for 23 weeks after completion of protocol therapy; must not be pregnant or nursing; women/men of reproductive potential must agree to use an effective contraceptive method as outlined in the study protocol. Men of reproductive potential must agree to use birth control throughout the study and for 31 weeks after completion of protocol therapy as outlined in the study protocol.
  • Must not have known active hepatitis B virus (HBV) or hepatitis virus (HCV) infection at time of registration; patients with HBV or HCV that have an undetectable viral load, or in the opinion of the treating investigator is well-controlled, are eligible.
  • Known to be human immunodeficiency virus (HIV)-positive at registration are eligible at time of registration if: Cluster of differentiation (CD)4+ cell count >/= 250 cells/mm^3; If on antiretroviral therapy, there must be minimal interactions or overlapping toxicity of the antiretroviral therapy with the experimental cancer treatment; once daily combinations that use pharmacologic boosters may not be used; No history of non-malignancy acquired immunodeficiency syndrome (AIDS)-defining conditions other than historical low CD4+ cell counts; Probable long-term survival with HIV if cancer were not present.

  • Exclusion Criteria

  • Had prior immune-related adverse event (grade 3 or higher immune-related pneumonitis, hepatitis, colitis, endocrinopathy) with prior immunotherapy (e.g. cancer vaccine, cytokine, etc.).
  • Have had or are planned for solid organ transplant; patients who have received allogeneic hematopoietic stem cell transplant are eligible if the transplant occurred at least 90 days prior to registration, patient has no prior acute graft versus host disease (GVHD), and within 48 hours of registration, patient demonstrates at least 90% engraftment, defined as: absolute neutrophil count (ANC) >= 500 mcl, measured over 3 consecutive days or 1 day with an ANC >= 1,000 mcl, or platelets >= 50,000 mcl measured, wherein the patient did not receive any platelet transfusions within 7 days prior to laboratory assessment, patients with autoimmune disease who are otherwise eligible under criterion 5.3 k must not have received steroid and immunosuppressive therapy within 28 days prior to registration
  • Currently receiving any other investigational agents or any other systemic anti-cancer therapy (including radiation); in event patient recently received any other systemic anti-cancer therapy, must be off therapy at least 7 days prior to registration and any therapy-induced toxicity must have recovered to less than or equal to grade 1.
  • Active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, immunosuppressive drugs, or corticosteroids with doses higher than prednisone 10 mg or equivalent). Replacement therapy is not considered a form of systemic treatment. Autoimmune diseases include but are not limited to autoimmune hepatitis, inflammatory bowel disease, multiple sclerosis, vasculitis, or glomerulonephritis. Some exceptions may apply as outlined in the protocol.
  • Any uncontrolled intercurrent illness including (not limited to): symptomatic congestive heart failure (CHF) (New York Heart Association [NYHA] III/IV), unstable angina pectoris or coronary angioplasty, or stenting within 24 weeks prior to registration, unstable cardiac arrhythmia (ongoing cardiac dysrhythmias of NCI Common Terminology Criteria for Adverse Events [CTCAE] version [v] 4 grade >= 2), known psychiatric illness that would limit study compliance, intra-cardiac defibrillators, known cardiac metastases, or abnormal cardiac valve morphology (>= grade 3).