Title
GU Hoosier HCRN GU21-517 A Phase 2 Study of Cabozantinib and Nivolumab in Metastatic Castration Resistant Prostate Cancer (CANOPY)

Description
This is a multicenter, single-arm, two-stage open-label phase 2 study of the combination of cabozantinib + nivolumab in subjects with advanced castration-resistant prostate cancer (CRPC).
Eligible subjects will undergo a baseline biopsy prior to treatment initiation. They will then initiate treatment with cabozantinib (40 mg orally daily) and nivolumab (480 mg intravenously every four weeks). An on-treatment biopsy will be performed during Cycle 2. Subjects will continue treatment until radiographic progression, toxicity or withdrawal. Prostate-specific antigen (PSA) levels will be evaluated once every cycle. Radiographic assessments will occur every two cycles for one year and then every three cycles thereafter. Cycle length is 28 days.

Objective
Primary Objective
1. Evaluate efficacy of the combination of cabozantinib + nivolumab via assessment of 6-month radiographic progression free survival (rPFS)

Secondary Objectives
1. PSA response as defined by PCWG3 criteria
2. ORR as defined by RECIST version 1.1
3. 6-month rPFS, PSA response defined by PCWG3 criteria, and ORR defined by RECIST version 1.1 in predefined subgroups:
a. Subjects with and without bone metastases.
b. Subjects with and without visceral metastases.
4. Conversion of circulating tumor cell (CTC) count from ?5 cells/7.5 mL blood at baseline to <5 cells/7.5 mL blood
confirmed by at least two readings 4 weeks apart.
5. Safety and tolerability as determined by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
6. Time to PSA progression as defined by PCWG3 criteria.26
7. Time to occurrence of first symptomatic skeletal event. A skeletal related event is the use of external beam radiotherapy
to relieve skeletal symptoms or the occurrence of new symptomatic pathological bone fractures (vertebral or nonvertebral)
or the occurrence of spinal cord compression or a tumor related orthopedic surgical intervention.
8. Evaluate time from treatment discontinuation to first subsequent anti-cancer therapy (including androgen receptor
signaling agents, cytotoxic chemotherapy, immunotherapy, or investigational agents) or death.
9. Evaluate rPFS.
10. Evaluate overall survival.

Treatment Experimental: Experimental Group
40 mg of cabozantinib taken orally every day (days 1-28) of a 28 day cycle
480 mg of nivolumab given intravenously on the first day (day 1) of each 28 day cycle
Drug: Cabozantinib
40 mg taken orally
Other Name: Cabometyx

Drug: Nivolumab
480 mg by infusion
Other Name: Opdivo

Key Eligibility For full study eligibility, see this study's clinicaltrials.gov record.

Applicable Disease Sites
Prostate

Participating Institutions
UW Health 1 S. Park Medical Center; UW Health Eastpark Medical Center; UW Health University Hospital