Protocol: 21-1020 / IRB21-1020
Phase: II
Investigator: Matthew Zibelman, MD
Disease(s): Kidney
Full Title: GU-187: Phase II Trial of Alternative Cabozantinib Dosing Schedule Alone and in Combination with Nivolumab in Metastatic Renal Cell Carcinoma

Study Summary

The purpose of this research study is to investigate alternative dosing schedules for the drug cabozantinib. Cabozantinib is a drug with FDA approval for metastatic renal cell carcinoma, but is not approved for the treatment of neuroendocrine tumors. Nivolumab is also a drug with FDA approval for metastatic renal cell carcinoma. Patients suffer from high rates of toxicities (side effects) from cabozantinib at its FDA-approved dose of 60 mg daily. This study aims to find better ways to adjust the dosing of this drug to decrease toxicities and increase how long the drug may be effective at controlling cancer growth and spread.

111 people will take part in this multicenter study

Before you begin the research study, you will need to complete some exams, tests, or procedures to find out if you can be in the research study. These exams, tests or procedures are part of regular cancer care and may be done even if you do not join the research study. If you have had some of them recently, they may not need to be repeated. This will be up to your study doctor.

If the screening procedures show you can take part in the study and you decide to take part in the study, you will be treated with cabozantinib or a combination of cabozantinib and nivolumab. Cabozantinib will be supplied by the sponsor of the trial. It is a pill or set of pills that will be taken daily at home on an empty stomach. The pill is to be swallowed with a glass of water with no food taken 2 hours before and 1 hour after the pill. You will begin treatment with 40 mg daily dose of the drug. The drug dosage may be increased or decreased depending on your tolerance and side-effects. Your treating physician may change your dosage during the study based on how you are doing.

You will be given sufficient pills for 30 days but you will be seen every 28 days, called a cycle. You will be asked to come to the clinic on the first day of each cycle but you will be seen or contacted more often during cycle 1 and cycle 2 of the study to adjust your dose of cabozantinib. A pill diary will be provided to you and it should be filled out each day.

If you are enrolled on the combination cabozantinib and nivolumab arm, cabozantinib will still be dispensed to you as described above, and nivolumab will be given to you intravenously (injection into your vein) on day 1 of every cycle.

Eligibility

To be eligible for this study, patients must meet several criteria, including but not limited to the following:

• Age > 18 years.
• Cohorts A and B: Histologically or cytologically confirmed advanced RCC with any clear cell or non-clear cell component. 100% sarcomatoid is permissible.
• Cohort C: Well differentiated neuroendocrine tumor (NET), grades 1-3 (any primary site) who have progressed on or are not eligible for somatostatin analogs per treating physician discretion.
• Patients may have had any number of prior therapies
• No evidence of pre-existing uncontrolled hypertension as assessed by investigator.
• No concomitant anticoagulation with coumarin agents (e.g., warfarin), direct thrombin inhibitors (e.g., dabigatran), direct factor Xa inhibitor betrixaban, or platelet inhibitors (e.g., clopidogrel).
• Cohort B only - cabozantinib + nivolumab: Active, known or suspected autoimmune disease is not allowed. Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger

ClinicalTrials.gov

Visit ClinicalTrials.gov for a full clinical trial description