Cabozantinib, Nivolumab, and Ipilimumab for the Treatment of Metastatic Non-clear Cell Renal Cell Cancer

Active:	Yes
Cancer Type:	Kidney Cancer	NCT ID:	NCT04413123
Trial Phases:	Phase II	Protocol IDs:	19-789 (primary) NCI-2020-11407
Eligibility:	18 Years and older, Male and Female	Study Type:	Treatment
Study Sponsor:	Dana-Farber Harvard Cancer Center
NCI Full Details:	http://clinicaltrials.gov/show/NCT04413123

Summary

This phase II trial studies the effect of cabozantinib, nivolumab, and ipilimumab for the treatment of non-clear cell renal cell cancer (kidney cancer) that has spread to other places in the body (metastatic). 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 tumor, and may interfere with the ability of tumor cells to grow and spread. The purpose of this trial is to assess whether cabozantinib, nivolumab, and ipilimumab in combination are safe and effective (how well the drug works) in slowing down the growth of kidney cancer.

Objectives

PRIMARY OBJECTIVE:
I. To determine the objective response rate (ORR) of cabozantinib combined with nivolumab plus ipilimumab in patients with non-clear cell renal cell carcinoma (nccRCC), defined as the percentage of patients with partial (PR) or complete response (CR) according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

SECONDARY OBJECTIVES:
I. To determine the duration of response to cabozantinib, nivolumab and ipilimumab in patients with advanced nccRCC.
II. To determine the progression-free survival (PFS) of patients with advanced nccRCC treated with cabozantinib, nivolumab and ipilimumab.
III. To determine the overall survival (OS) of patients with advanced nccRCC treated with cabozantinib, nivolumab and ipilimumab.
IV. To determine ORR, PFS and OS of patients with advanced nccRCC treated with cabozantinib, nivolumab and ipilimumab, according to pre-specified subgroups (these groups are not used for stratification purposes):
IVa. Histological subtypes (papillary versus non-papillary; presence of sarcomatoid differentiation [yes/no]).
IVb. International metastatic renal cell carcinoma database (IMDC) risk groups (favorable versus intermediate versus poor).
IVc. Lines of previous therapy (treatment naïve versus previously treated).
IVd. PD-L1 expression on tumor and immune cells (positive versus negative).
V. To assess the safety of cabozantinib combined with nivolumab and ipilimumab in patients with advanced nccRCC according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
VI. To assess the impact of cabozantinib, nivolumab and ipilimumab on quality of life in patients with advanced nccRCC, using the Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI)-19 and the Brief Fatigue Inventory (BFI) to be assessed with each computed tomography (CT) scan.

EXPLORATORY OBJECTIVES:
I. To evaluate heterogeneity of immune markers and molecular features between archival tumor tissue and fresh tumor samples collected at baseline.
II. To evaluate the immune modifications mediated by the combination of cabozantinib, nivolumab and ipilimumab in patients with advanced nccRCC, using fresh tumor tissue and blood samples before and on therapy.
III. To evaluate the immunologic and molecular correlates of response and survival in patients with advanced nccRCC treated with cabozantinib, nivolumab and ipilimumab, from fresh tumor tissue and blood samples collected before therapy.
IV. To identify the immune and molecular mechanisms of resistance to cabozantinib, nivolumab and ipilimumab in patients with advanced nccRCC, using fresh tumor tissue collected at the time of radiographic progression, and blood samples collected before and on therapy.

OUTLINE:
Patients receive cabozantinib orally (PO), nivolumab intravenously (IV), and ipilimumab IV on study.

After completion of study, patients are followed up for 90 days, and then every 6 months for 2 years.

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