Nivolumab Combined With Ipilimumab for Patients With Advanced Rare Genitourinary Tumors

NCT03333616 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 17-423
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 6

Brief Summary

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

Conditions

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

Keywords

Genitourinary Cancer

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate

  Radiologic disease assessment performed at 12 weeks after initial treatment and then every 6 or 12 weeks. These radiologic disease assessments are evaluated per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 guidelines. This will be conducted by cohort ((1) ACC, (2) Non-urothelial bladder/upper tract cancer and (3) other rare GU tumors)

  Imaging will occur every 6-12 weeks study entry up until disease progression (up to 24 months)

Secondary Outcomes (6)

• Objective Response Rate for all rare GU tumor types

  Imaging will occur every 6-12 weeks study entry up until disease progression (up to 24 months)

• Duration of Response

  Imaging will occur every 6-12 weeks study entry up until disease progression (up to 24 months)

• Immune related objective response rate

  Imaging will occur every 6-12 weeks study entry up until disease progression (up to 24 months)

• Progression-Free Survival for the total cohort and by tumor cohort

  From start of treatment until date of death from any cause (average 24 months)

• Overall Survival for all patients and by tumor cohort

  From start of treatment until date of death from any cause. (Average 24 months)

Study Arms (1)

Nivolumab+Ipilimumab

EXPERIMENTAL

* Nivolumab and Ipilimumab are administered intravenously every 3 weeks for a total of 4 maximum doses. After combination therapy, nivolumab will be administered as monotherapy every 4 weeks. * Doses are determined per protocol.

Drug: Ipilimumab; Drug: Nivolumab

Interventions

Ipilimumab DRUG

is an immunotherapy medication that stimulates the immune system to fight cancer cells throughout the body.

Also known as: Yervoy

Nivolumab+Ipilimumab

Nivolumab DRUG

Nivolumab binds to and blocks the activation of PD-1. This results in the activation of T-cells and cell-mediated immune responses against tumor cells

Also known as: Opdivo

Nivolumab+Ipilimumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

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.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Bristol-Myers Squibb: collaborator

Study Sites (6)

University of California, San Diego Moores Cancer Center

La Jolla, California, 92093, United States

Location

Winship Cancer Institute, Emory University

Atlanta, Georgia, 30322, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02115, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• McGregor BA, Campbell MT, Xie W, Farah S, Bilen MA, Schmidt AL, Sonpavde GP, Kilbridge KL, Choudhury AD, Mortazavi A, Shah AY, Venkatesan AM, Bubley GJ, Siefker-Radtke AO, McKay RR, Choueiri TK. Results of a multicenter, phase 2 study of nivolumab and ipilimumab for patients with advanced rare genitourinary malignancies. Cancer. 2021 Mar 15;127(6):840-849. doi: 10.1002/cncr.33328. Epub 2020 Nov 20.

  PMID: 33216356 DERIVED

MeSH Terms

Conditions

Urogenital Neoplasms; Adrenocortical Carcinoma; Penile Neoplasms; Carcinoma, Small Cell

Interventions

Ipilimumab; Nivolumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Adrenal Cortex Neoplasms; Adrenal Gland Neoplasms; Endocrine Gland Neoplasms; Adrenal Cortex Diseases; Adrenal Gland Diseases; Endocrine System Diseases; Genital Neoplasms, Male; Genital Diseases, Male; Genital Diseases; Penile Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Bradley A McGregor, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 30, 2017
• First Posted: November 7, 2017
• Study Start: December 28, 2017
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: January 21, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)