This phase II trial tests whether using genetic testing of tumor tissue to select the optimal treatment regimen works in treating patients with clear cell renal cell (kidney) cancer that has spread to other places in the body (advanced or metastatic). The current Food and Drug Administration (FDA)-approved regimens for advanced kidney cancer fall into two categories. One treatment combination includes two immunotherapy drugs (nivolumab plus ipilimumab), which are delivered by separate intravenous infusions into a vein. The other combination is one immunotherapy drug (nivolumab infusion) plus an oral pill taken by mouth (cabozantinib). Nivolumab and ipilimumab are "immunotherapies" which release the brakes of the immune system, thus allowing the patient's own immune system to better kill cancer cells. Cabozantinib is a "targeted therapy" specifically designed to block certain biological mechanisms needed for growth of cancer cells. In kidney cancer, cabozantinib blocks a tumor's blood supply. The genetic (DNA) makeup of the tumor may affect how well it responds to therapy. Testing the makeup (genes) of the tumor, may help match a treatment (from one of the above two treatment options) to the specific cancer and increase the chance that the disease will respond to treatment. The purpose of this study is to learn if genetic testing of tumor tissue may help doctors select the optimal treatment regimen to which advanced kidney cancer is more likely to respond.
Histological confirmation of RCC with a clear cell component
Advanced (not amenable to curative surgery or radiation therapy) or metastatic (American Joint Committee on Cancer [AJCC] stage IV) RCC
Patient can comprehend and sign the study informed consent form
Male or female >= 18 years of age at the time of informed consent
Major surgery requiring general anesthesia
Inadequately controlled hypertension (systolic blood pressure [SBP] > 160/90 mmHg)
Anti-hypertensive medications are permitted.
Active infection requiring infusional treatment
Parallel
Cabozantinib
DrugGiven PO
Ipilimumab
Biological/VaccineGiven IV
Nivolumab
Biological/VaccineGiven IV
Overall response rate (ORR) (Arm 1)
Assessed per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. ORR = complete response (CR) + partial response (PR). The Agresti-Coull two-sided 95% confidence intervals (CIs) for the success rate will be reported.
Overall response rate (Arm 2)
Assessed per RECIST 1.1. ORR = CR + PR. The Agresti-Coull two-sided 95% CIs for the success rate will be reported.
Progression free survival
Possible risk factors will be compared for survival with Kaplan-Meier estimates and log-rank tests. The proportional hazards model will be used for adjusting tests of significance and estimating the hazard ratios. Will apply the generalized estimating equation (GEE) statistical procedure for longitudinal binary data analysis with multiple observable vectors for the same subject. For the continuous multiple time points or correlated data, will use the mixed effects model to conduct the profile analysis. The adjusted 95% CIs will be reported.
Depth of response > 80%
Will apply the GEE statistical procedure for longitudinal binary data analysis with multiple observable vectors for the same subject. For the continuous multiple time points or correlated data, will use the mixed effects model to conduct the profile analysis. The adjusted 95% CIs will be reported.
Incidence of immune-related adverse events
Adverse medical events will be tabulated. National Cancer Institute toxicity grade 3 and grade 4 laboratory abnormalities will be listed.
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Vanderbilt-Ingram Cancer Center
Lead sponsor
National Cancer Institute (NCI)
Collaborator
United States Department of Defense
Collaborator
