Testing the Effectiveness of Two Immunotherapy Drugs (Nivolumab and Ipilimumab) With One Anti-cancer Targeted Drug (Cabozantinib) for Rare Genitourinary Tumors

Stage IVB Prostate Cancer AJCC v8 Clinical Trial

Official title: A Phase II Study of Ipilimumab, Cabozantinib, and Nivolumab in Rare Genitourinary Cancers (ICONIC)

Status Recruiting

Clinical Trial Summary

This phase II trial studies how well cabozantinib works in combination with nivolumab and ipilimumab in treating patients with rare genitourinary (GU) tumors that has spread from where it first started (primary site) to other places in the body. Cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving cabozantinib, nivolumab, and ipilimumab may work better in treating patients with genitourinary tumors that have no treatment options compared to giving cabozantinib, nivolumab, or ipilimumab alone.

Clinical Trial Description

PRIMARY OBJECTIVE:

I. To evaluate the efficacy of cabozantinib s-malate (cabozantinib) combined with nivolumab and ipilimumab in the first or second-line (and beyond) setting for patients within each of the rare genitourinary (GU) variant histology group of interest, as measured by objective response rate (ORR).

SECONDARY OBJECTIVES:

I. To estimate the progression-free survival (PFS) for patients treated with cabozantinib combined with nivolumab and ipilimumab within each rare variant histology.

II. To estimate the overall survival (OS) for patients treated with cabozantinib combined with nivolumab and ipilimumab within each rare variant histology.

III. To estimate the clinical benefit rate (defined as complete response [CR] or partial response [PR] or stable disease [SD]) for patients treated with cabozantinib combined with nivolumab and ipilimumab within each rare variant histology.

IV. To assess the safety of treating patients with rare variant histologies with cabozantinib combined with nivolumab and ipilimumab.

V. To support tissue banking and collection of clinical follow-up data for GU tract rare histological variants.

EXPLORATORY OBJECTIVE:

I. To assess effects of treatment in patients with bone-only disease by bone scan.

OUTLINE:

Patients receive cabozantinib orally (PO) once daily (QD) on days 1-21 of cycles 1-4 and on days 1-28 of subsequent cycles. Patients also receive nivolumab intravenously (IV) over 30 minutes on day 1 and ipilimumab IV over 90 minutes on day 1 of cycles 1-4. Patients then receive nivolumab IV over 30 minutes on day 1 of subsequent cycles. Treatment repeats every 21 days for cycles 1-4 and every 28 days for subsequent cycles for 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT) or magnetic resonance imaging (MRI), and bone scan throughout the trial and may undergo positron emission tomography (PET)/CT throughout the trial.

After completion of study treatment, patients are followed up every 2 months for up to 5 years. ;

Related Conditions & MeSH terms

• Adenocarcinoma
• Bladder Adenocarcinoma
• Bladder Clear Cell Adenocarcinoma
• Bladder Mixed Adenocarcinoma
• Bladder Neuroendocrine Carcinoma
• Bladder Small Cell Neuroendocrine Carcinoma
• Bladder Squamous Cell Carcinoma
• Carcinoma
• Carcinoma, Neuroendocrine
• Carcinoma, Renal Cell
• Carcinoma, Small Cell
• Carcinoma, Squamous Cell
• Carcinoma, Transitional Cell
• Chromophobe Renal Cell Carcinoma
• Collecting Duct Carcinoma
• Kidney Medullary Carcinoma
• Large Cell Neuroendocrine Carcinoma
• Leydig Cell Tumor
• Metastatic Bladder Carcinoma
• Metastatic Bladder Large Cell Neuroendocrine Carcinoma
• Metastatic Bladder Small Cell Neuroendocrine Carcinoma
• Metastatic Bladder Squamous Cell Carcinoma
• Metastatic Kidney Medullary Carcinoma
• Metastatic Malignant Genitourinary System Neoplasm
• Metastatic Papillary Renal Cell Carcinoma
• Metastatic Penile Carcinoma
• Metastatic Prostate Small Cell Neuroendocrine Carcinoma
• Metastatic Sarcomatoid Renal Cell Carcinoma
• Metastatic Urethral Carcinoma
• Neoplasms
• Papillary Renal Cell Carcinoma
• Penile Neoplasms
• Sarcomatoid Renal Cell Carcinoma
• Stage IV Bladder Cancer AJCC v8
• Stage IV Penile Cancer AJCC v8
• Stage IV Renal Cell Cancer AJCC v8
• Stage IV Urethral Cancer AJCC v8
• Stage IVB Prostate Cancer AJCC v8
• Thyroid Neoplasms
• Urethral Clear Cell Adenocarcinoma
• Urethral Neoplasms
• Urinary Bladder Neoplasms

• NCT number: NCT03866382
• Study type: Interventional
• Source: National Cancer Institute (NCI)
• Status: Recruiting
• Phase: Phase 2
• Start date: May 13, 2019
• Completion date: February 28, 2025