Testing the Effectiveness of Two Immunotherapy Drugs (Nivolumab and Ipilimumab) With One Anti-cancer Targeted Drug (Cabozantinib) for Rare Genitourinary Tumors
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|ClinicalTrials.gov Identifier: NCT03866382|
Recruitment Status : Recruiting
First Posted : March 7, 2019
Last Update Posted : September 28, 2023
|Condition or disease||Intervention/treatment||Phase|
|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||Procedure: Bone Scan Drug: Cabozantinib S-malate Procedure: Computed Tomography Biological: Ipilimumab Procedure: Magnetic Resonance Imaging Biological: Nivolumab Procedure: Positron Emission Tomography||Phase 2|
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).
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.
I. To assess effects of treatment in patients with bone-only disease by bone scan.
Patients receive cabozantinib orally (PO), nivolumab intravenously (IV) and ipilimumab IV while on study. Patients undergo computed tomography (CT) scan, magnetic resonance imaging (MRI), positron emission tomography (PET) and bone scans throughout the study.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||224 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Study of Ipilimumab, Cabozantinib, and Nivolumab in Rare Genitourinary Cancers (ICONIC)|
|Actual Study Start Date :||May 13, 2019|
|Estimated Primary Completion Date :||February 29, 2024|
|Estimated Study Completion Date :||February 29, 2024|
Experimental: Treatment (cabozantinib, nivolumab, ipilimumab)
Patients receive cabozantinib PO, nivolumab IV and ipilimumab IV while on study. Patients undergo CT scan, MRI, PET and bone scans throughout the study.
Procedure: Bone Scan
Undergo bone scan
Other Name: Bone Scintigraphy
Drug: Cabozantinib S-malate
Procedure: Computed Tomography
Undergo CT scan
Procedure: Magnetic Resonance Imaging
Procedure: Positron Emission Tomography
Undergo PET scan
- Objective response rate (ORR) [ Time Frame: Up to 5 years ]An objective response is defined as a confirmed complete response (CR) or partial response (PR) as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. A confirmed tumor response is defined to be either a CR or PR noted as the objective status on 2 consecutive evaluations at least 4 weeks apart. Will be estimated by the number of confirmed objective responses divided by the total number of evaluable patients. Confidence intervals for the true ORR will be calculated.
- Duration of response [ Time Frame: From time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 5 years ]Defined for all evaluable patients who have achieved an objective response as the date at which the patient's earliest best objective status is first noted to be either a CR or PR to the earliest date progression is documented.
- Progression-free survival (PFS) [ Time Frame: From start of treatment to time of progression or death, whichever occurs first, assessed up to 5 years ]The median its 95% confidence interval will be determined and will be summarized using the Kaplan-Meier estimator.
- Overall survival [ Time Frame: Up to 5 years ]The median its 95% confidence interval will be determined and will be summarized using the Kaplan-Meier estimator.
- Clinical benefit rate (CBR) [ Time Frame: Up to 5 years ]A confirmed clinical benefit is defined to be either a CR or PR noted as the objective status on 2 consecutive evaluations at least 4 weeks apart or a confirmed stable disease at two consecutive tumor assessments at least 3 months apart. The CBR will be estimated by the number of patients with confirmed clinical benefit divided by the total number of evaluable patients. Confidence intervals for the true CBR will be calculated using exact binomial confidence intervals.
- Incidence of adverse events (AE) [ Time Frame: Up to 5 years ]Will be assessed using Common Terminology Criteria for Adverse Events version 5.0. The maximum of a particular AE will be determined for each patient. Tables will summarize the number and relative frequency of patients observing an AE as well as the number and relative frequency of patients experiencing any AE of grade 3 or greater.
- Effects of treatment in patients with bone-only disease [ Time Frame: Up to 5 years ]The bone-only tumor patients will be evaluated in an exploratory fashion (if no RECIST measurements are available). A maximum of 15 patients with bone-only disease will be enrolled and evaluated using PFS for a descriptive analysis of the effect of treatment.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03866382
|Principal Investigator:||Andrea B Apolo||Alliance for Clinical Trials in Oncology|