Trials / Recruiting
RecruitingNCT03866382
Testing the Effectiveness of Two Immunotherapy Drugs (Nivolumab and Ipilimumab) With One Anti-cancer Targeted Drug (Cabozantinib) for Rare Genitourinary Tumors
A Phase II Study of Ipilimumab, Cabozantinib, and Nivolumab in Rare Genitourinary Cancers (ICONIC)
- Status
- Recruiting
- Phase
- Phase 2
- Study type
- Interventional
- Enrollment
- 314 (estimated)
- Sponsor
- National Cancer Institute (NCI) · NIH
- Sex
- All
- Age
- 18 Years
- Healthy volunteers
- Not accepted
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.
Detailed 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 may undergo echocardiography during screening and undergo computed tomography (CT) or magnetic resonance imaging (MRI), bone scan and blood and urine sample collection 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.
Conditions
- Bladder Adenocarcinoma
- Bladder Clear Cell Adenocarcinoma
- Bladder Mixed Adenocarcinoma
- Bladder Neuroendocrine Carcinoma
- Bladder Small Cell Neuroendocrine Carcinoma
- Bladder Squamous Cell Carcinoma
- Chromophobe Renal Cell Carcinoma
- Collecting Duct Carcinoma
- Invasive Bladder Giant Cell Urothelial Carcinoma
- Invasive Bladder Lymphoepithelioma-Like Carcinoma
- Invasive Bladder Nested Urothelial Carcinoma
- Invasive Bladder Plasmacytoid Urothelial Carcinoma
- Invasive Bladder Sarcomatoid Urothelial Carcinoma
- Invasive Bladder Urothelial Carcinoma
- Kidney Medullary Carcinoma
- Large Cell Neuroendocrine Carcinoma
- Malignant Testicular Leydig Cell Tumor
- Malignant Testicular Sertoli Cell Tumor
- Metastatic Bladder Carcinoma
- Metastatic Bladder Clear Cell (Glycogen-Rich) Urothelial Carcinoma
- Metastatic Bladder Giant Cell Urothelial Carcinoma
- Metastatic Bladder Large Cell Neuroendocrine Carcinoma
- Metastatic Bladder Lipid-Rich Urothelial Carcinoma
- Metastatic Bladder Micropapillary Urothelial Carcinoma
- Metastatic Bladder Plasmacytoid Urothelial Carcinoma
- Metastatic Bladder Sarcomatoid Urothelial Carcinoma
- Metastatic Bladder Small Cell Neuroendocrine Carcinoma
- Metastatic Bladder Squamous Cell Carcinoma
- Metastatic Chromophobe Renal 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
- Papillary Renal Cell Carcinoma
- 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
- Urachal Adenocarcinoma
- Urethral Clear Cell Adenocarcinoma
Interventions
| Type | Name | Description |
|---|---|---|
| PROCEDURE | Biospecimen Collection | Undergo blood and urine sample collection |
| PROCEDURE | Bone Scan | Undergo bone scan |
| DRUG | Cabozantinib S-malate | Given PO |
| PROCEDURE | Computed Tomography | Undergo CT and/or PET/CT scan |
| PROCEDURE | Echocardiography Test | Undergo echocardiography |
| BIOLOGICAL | Ipilimumab | Given IV |
| PROCEDURE | Magnetic Resonance Imaging | Undergo MRI |
| BIOLOGICAL | Nivolumab | Given IV |
| PROCEDURE | Positron Emission Tomography | Undergo PET/CT scan |
Timeline
- Start date
- 2019-05-13
- Primary completion
- 2027-02-28
- Completion
- 2027-02-28
- First posted
- 2019-03-07
- Last updated
- 2026-04-16
Locations
580 sites across 2 countries: United States, Puerto Rico
Regulatory
- FDA-regulated drug study
Source: ClinicalTrials.gov record NCT03866382. Inclusion in this directory is not an endorsement.