Clinical Trial: Cabozantinib-s-malate and Nivolumab With or Without Ipilimumab in Treating Patients With Metastatic Genitourinary Tumors

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Phase 1 Study of Cabozantinib Plus Nivolumab (CaboNivo) Alone or in Combination With Ipilimumab (CaboNivoIpi) in Patients With Advanced/Metastatic Urothelial Carcinoma and Other Genitourinary Tumors

Brief Summary: This phase I trial studies the side effects and best doses of cabozantinib-s-malate and nivolumab with or without ipilimumab in treating patients with genitourinary (genital and urinary organ) tumors that have spread to other places in the body. Cabozantinib-s-malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as nivolumab and ipilimumab, may block tumor growth in different ways by targeting certain cells. It is not yet known whether giving cabozantinib-s-malate and nivolumab alone or with ipilimumab works better in treating patients with genitourinary tumors.

Detailed Summary:

PRIMARY OBJECTIVES:

I. Determine the dose limiting toxicity (DLT) and recommended phase II dose (RP2D) of the combination of cabozantinib (cabozantinib-s-malate) and nivolumab (cabo-nivo) and separately the combination of cabozantinib, nivolumab and ipilimumab (cabo-nivo-ipi) in patients with genitourinary tumors. (Phase I) II. Assess safety and tolerability of cabozantinib, nivolumab and ipilimumab (cabo-nivo-ipi) in patients with genitourinary tumors at this novel dose. (Dose Level 8 Cohort)

SECONDARY OBJECTIVES:

I. Preliminarily evaluate the activity, as determined by objective response rate using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and the modified Immune-Related Response Criteria (irRC), derived from RECIST1.1, of cabo-nivo and cabo-nivo-ipi in patients with advanced/refractory metastatic urothelial carcinoma (checkpoint inhibition therapy naive) and with renal cell carcinoma in the second-line and beyond setting.

II. Preliminarily evaluate the activity, as determined by objective response rate using RECIST 1.1 and the modified irRC, derived from RECIST 1.1, of cabo-nivo in patients with adenocarcinoma and with squamous cell carcinoma of the bladder in the first line or beyond setting.

III. Preliminarily evaluate the activity, as determined by objective response rate using RECIST 1.1 and the modified irRC, derived from RECIST 1.1, of cabo-nivo in patients with urothelial carcinoma previously treated with checkpoint inhibition therapy in the second line or beyond setting.

IV. Preliminarily evaluate the activity, as determined by objective response rate using RECIST 1.1 and the modified irRC, derived f
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome:

  • Incidence of adverse events evaluated according National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (Phase I) [ Time Frame: Up to 3 years ]
    The safety and tolerability of a novel dose of cabozantinib, nivolumab and ipilimumab in patients with genitourinary cancer will be assessed.
  • Recommended phase II dose defined as the highest dose for which no more than 1/6 patients experience a dose limiting toxicity evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (Phase I) [ Time Frame: Up to 4-6 weeks ]
    The safe dose level of cabozantinib and nivolumab, as well as of cabozantinib, nivolumab, and ipilimumab will be established.


Original Primary Outcome: RP2D for the Cabo/Nivo and Cabo/Nivo/Ipi combinations separately [ Time Frame: Dose Limiting Toxicity ]

Current Secondary Outcome:

  • Clinical response rate assessed by Response Evaluation Criteria in Solid Tumors 1.1 and Immune-Related Response Criteria [ Time Frame: Up to 3 years ]
    The response rate may be used to guide the further development of the combinations.
  • Fraction of patients who have been identified as being alive and progression free at two months [ Time Frame: At 2 months ]
    May be determined as well and reported on both arms. This fraction will be considered as a secondary endpoint for the expansion cohorts as well, and this information may be used to guide the further development of the combinations. A Kaplan-Meier curve for progression free survival will also be presented as a secondary endpoint, in addition to reporting the fraction without progression at two months.
  • PDL-1 and MET expression [ Time Frame: Up to day 1 of final course ]
    PDL-1 and MET expression data will be obtained in patients with urothelial carcinoma checkpoint inhibition naive, clear cell renal cell carcinoma, adenocarcinoma of the bladder, squamous cell carcinoma of the bladder, urothelial carcinoma with prior checkpoint inhibition therapy, and penile cancer. Data will be obtained in pre- and post-treatment biopsies and analyze, in at least an exploratory fashion, their association to response or clinical benefit.


Original Secondary Outcome:

Information By: National Cancer Institute (NCI)

Dates:
Date Received: July 8, 2015
Date Started: July 2015
Date Completion:
Last Updated: May 19, 2017
Last Verified: March 2017