Nivolumab Combined With Ipilimumab for Patients With Advanced Rare Genitourinary Tumors

Running, not enrolling · Phase 2

Conditions studied: Genitourinary Cancer, Adrenocortical Carcinoma, Non-urothelial Bladder, Non-urothelial Upper Tract, Penile Cancer, Non-adenocarcinoma Prostate Cancer, Refractory Germ-cell, High Grade Neuroendocrine Carcinoma/Small Cell Carcinoma

In brief

This research study is studying a combination of drugs as a possible treatment for rare genitourinary malignancies among four cohorts, bladder or upper tract carcinoma with variant histology, adrenocortical carcinoma, other rare genitourinary carcinomas and any genitourinary carcinoma with neuroendocrine differentiation. Given preliminary results, the study is being tested in additional patients with bladder or upper tract carcinoma with variant histology at this time while the adrenocortical carcinoma, other rare genitourinary malignancies arms have closed to accrual -The names of the study drugs involved in this study are: * Nivolumab * Ipilimumab

Key facts

Study ID

NCT03333616

Run by

Dana-Farber Cancer Institute

People needed

100

Starts

2017-12-28

Expected to finish

2027-06-28

Last updated by the study team

2026-07-23

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Age ≥ 18 years at the time of consent.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2 within 28 days prior to registration (Appendix A).
• Unresectable advanced or metastatic ACC, non-urothelial bladder/upper tract cancer, non-adenocarcinoma prostate cancer, penile cancer, treatment refractory germ-cell tumor or a high grade neuroendocrine carcinoma/small cell carcinoma of any genitourinary site. Pure is defined as >90% and those with a portion of urothelial carcinoma or prostate adenocarcinoma may be included at discretion of the principal investigator. With variant histology in the primary, if metastatic biopsy shows pure variant histology, patient is eligible.
• at this time only the bladder and neuroendocrine cohorts are open
• Availability of Formalin-fixed, Paraffin-embedded (FFPE) archival tumor specimens, when available, and willingness of the subject to undergo mandatory fresh tumor biopsy prior to treatment initiation unless determined medically unsafe or not feasible.
• The archival specimen, when available, must contain adequate viable tumor tissue.
• The specimen may consist of a tissue block (preferred and should contain the highest grade of tumor) or at least 20 unstained serial sections. Fine-needle aspiration, brushings, cell pellet from pleural effusion, bone marrow aspirate/biopsy are not acceptable.
• A mandatory biopsy at the time of radiographic progression will be requested from patients who have an initial response to treatment and then subsequently progress as determined by RECIST version 1.1.
• Measurable disease as defined by RECIST 1.1 within 28 days prior to registration.
• Demonstrate adequate organ function. All screening labs to be obtained within 28 days prior to first study treatment.
• Hematological
• White blood cell (WBC) ≥ 2000 cells/µL
• Absolute Neutrophil Count (ANC) ≥ 1000 cells/µL
• Platelet count (plt) ≥ 75,000/ µL
• Hemoglobin (Hgb) ≥ 9 g/dL
• Absolute lymphocyte count ≥ 500 cells/µL
• Renal
• Serum creatinine OR
• Calculated creatinine clearance1 ≤ 1.5 x ULN ≥ 40 mL/min
• Hepatic and Other
• Bilirubin ≤ 1.5 × upper limit of normal (ULN)
• AST2 ≤ 2.5 × ULN
• ALT2 ≤ 2.5 × ULN
• Alkaline Phosphatase2 ≤ 2.5 × ULN
• Albumin > 2.5 g/dL

You may not qualify if…

• Prior use of systemic checkpoint inhibitors (including PD-1, PD-L1, and CTLA-4 targeting agents) for the management of ACC, non-urothelial bladder cancer/upper tract, non-adenocarcinoma prostate cancer, penile cancer or treatment refractory germ-cell tumor is excluded
• Treatment with systemic immunosuppressive medications including but not limited to: prednisone, dexamethasone, cyclosporine, azathioprine, methotrexate, thalidomide, anti-tumor necrosis factor (TNF) agents within 2 weeks of first study dose.
• Subjects who have received acute, low-dose systemic immunosuppressant medications may be enrolled (such as steroids for acute nausea or cancer-related pain ≤ 10 mg prednisone) maybe enrolled sooner than 2 weeks of first study dose.
• Subjects with adrenal insufficiency on physiologic replacement doses of steroids may be enrolled (≤ 10 mg prednisone).
• The use of inhaled, topical, ocular or intra-articular corticosteroids and mineralocorticoids are allowed.
• Treatment with chemotherapy, hormone therapy, or other investigational therapy within 3 weeks of first study doses. Patients with non-adenocarcinoma of the prostate who may be on luteinizing hormone-releasing hormone agonist/antagonist therapy may continue use. For ACC patients, hormonal agents (e.g mitotane) are allowed for the purpose to control endocrine-related symptoms when needed.
• Radiotherapy within 14 days of first study treatment with the exception of a single fraction of radiation administered for palliation of symptoms.
• Known active metastases to the brain, spinal cord or leptomeninges. Patients who are treated with radiotherapy, radiosurgery, or surgery and clinically stable for at least 2 weeks of first study treatment are eligible. Repeat imaging is not required to document treatment response.
• Malignancies other than ACC, non-urothelial bladder/upper tract cancer, non-adenocarcinoma prostate cancer, penile cancer, treatment refractory germ-cell tumor or genitourinary high grade neuroendocrine carcinoma/small cell carcinoma within 5 years of first study treatment with the exception of those with negligible risk of metastases or death and/or treated with expected curative outcome (included but not limited to carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer for patients with malignancies other than non-adenocarcinoma of the prostate, ductal carcinoma in situ of the breast, non-muscle invasive urothelial carcinoma of the bladder for patients with malignancies other than non-urothelial bladder cancer).
• History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion protein.
• Known hypersensitivity to any component of the nivolumab or ipilimumab product.
• Any active or recent history (within 6 months of first study dose) of autoimmune disease or syndrome that requires systemic corticosteroids (>10 mg daily prednisone equivalent) or immunosuppressive medications including but not limited to: myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with anti-phospholipid syndrome, Wegner's granulomatosis, Sjogren's syndrome, Guillain-Barre syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. Subjects with vitiligo, controlled type I diabetes mellitus, residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement therapy are permitted to enroll.
• Any condition requiring treatment with corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medication within 14 days of the first dose of study drug. Inhaled, topical, ocular or intra-articular corticosteroids and adrenal replacement steroid doses ≤ 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
• Uncontrolled adrenal insufficiency.
• History of idiopathic pulmonary fibrosis, organized pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening imaging CT of the chest. History of radiation pneumonitis in the radiation field is permitted.
• Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome.
• Active or chronic hepatitis B infection (defined as having a positive hepatitis B surface antigen (HBsAg) test at screening). Subject with past or resolved hepatitis B infection (defined as having a negative HBsAg test and positive antibody to hepatitis B core antigen test) are eligible. Hepatitis B viral DNA must be obtained in Subjects with positive hepatitis B core antibody prior to first treatment start.
• Active hepatitis C infection. Subjects positive hepatitis C antibody test are eligible if PCR is negative for hepatitis C viral DNA.
• Receipt of therapeutic oral or IV antibiotics within 2 weeks of first study treatment. Subjects receiving routine antibiotic prophylaxis (for dental extractions/procedures) are eligible.
• Active infection requiring systemic treatment.
• Significant cardiovascular disease such New York Heart Association (NYHA) class III or greater, myocardial infarction within the previous 3 months, unstable arrhythmias, unstable angina, need for cardiac angioplasty or stenting, coronary artery by-pass graft surgery, symptomatic peripheral vascular disease. Subjects with known coronary artery disease treated with stenting or coronary artery by-pass graft, congestive heart failure not meeting the above criteria, or left ventricular ejection fraction < 50% must be on a stable regimen that is optimized in the opinion of the treating physician, in consultation with a cardiologist when appropriate.
• Prolongation of the QTcF interval defined as > 450 msec for males and > 470 msec for females.
• Inadequately controlled hypertension (defined as systolic blood pressure > 160 mmHg and/or diastolic blood pressure > 100 mmHg). Anti-hypertensive therapy to achieve these parameters is allowed.
• History of cerebrovascular accident or transient ischemic attack within 3 months of first study dose.
• Significant vascular disease (such as aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 3 months of first study dose.

Where it is running

• University of California, San Diego Moores Cancer Center — La Jolla, California, United States
• Winship Cancer Institute, Emory University — Atlanta, Georgia, United States
• Beth Israel Deaconess Medical Center — Boston, Massachusetts, United States
• Dana-Farber Cancer Institute — Boston, Massachusetts, United States
• Ohio State University Comprehensive Cancer Center — Columbus, Ohio, United States
• MD Anderson Cancer Center — Houston, Texas, United States

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.