Study of Cabozantinib and Nivolumab in Metastatic Castration Resistant Prostate Cancer

NCT05502315 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: HCRN GU21-517
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 4

Brief Summary

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).

Conditions

Metastatic Cancer; Castration-resistant Prostate Cancer

Keywords

Castration resistant prostate cancer; Immunotherapy; Targeted therapy; Bone metastases

Outcome Measures

Primary Outcomes (1)

• Radiographic Progression Free Survival (rPFS)

  The primary endpoint is the efficacy of treatment via assessment of 6 month rPFS defined by RECIST version 1.1 for soft tissue and Prostate Cancer Working Group 3 (PCWG3) criteria for bone metastases. rPFS is defined as the duration of time from the first day of the start of study treatment to time of radiographic progression or death due to any cause, whichever occurs first.

  6 months

Secondary Outcomes (12)

• PSA Response

  3 years

• Overall Response Rate (ORR)

  3 years

• 6-month rPFS in predefined subgroups

  6 months

• 6-month PSA response in predefined subgroups

  6 months

• 6-month ORR in predefined subgroups

  6 months

Study Arms (1)

Experimental Group

EXPERIMENTAL

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; Drug: Nivolumab

Interventions

Cabozantinib DRUG

40 mg taken orally

Also known as: Cabometyx

Experimental Group

Nivolumab DRUG

480 mg by infusion

Also known as: Opdivo

Experimental Group

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Biologically male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing and able to provide, or have a legally authorized representative provide, written informed consent and HIPAA authorization for the release of personal health information. A signed informed consent must be obtained before screening procedures are performed. NOTE: HIPAA authorization may be either included in the informed consent or obtained separately.
• Males 18 years of age and above.
• Histological or cytological proof of prostate adenocarcinoma or mixed adenocarcinoma/neuroendocrine tumors. Pure small cell of the prostate is not allowed.
• ECOG status of ≤ 2
• Progressive mCRPC as defined: 1) castrate levels of serum testosterone \< 50 ng/dL AND 2) progressive disease as defined by PSA or radiographic progression. Subjects with measurable and non-measurable disease (i.e., bone only metastases) are allowed. NOTE: ENROLLMENT of subjects with non-measurable disease (i.e., bone only metastases) will be capped at 50% of enrollment target (n=25).
• Must have exposure to one prior taxane (or be taxane ineligible or refuse taxane) AND one prior AR-targeting agent (for example, abiraterone, enzalutamide, apalutamide, darolutamide). Receipt of taxane or AR-targeting agent may be in the hormone sensitive or castration resistant setting. Subjects may have received more than 1 prior Androgen receptor signaling inhibitors (ARSI). Subjects may have had prior 177Lu-PSMA-617.
• Recovery to baseline or ≤ Grade 1 CTCAE v5.0 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy.
• Normal organ function with acceptable initial laboratory values within 14 days of treatment start:
• WBC: ≥ 2,500/mcL
• ANC: ≥ 1,500/mcL
• Hemoglobin: ≥ 9 g/dL (transfusions are permitted)
• Platelet count: ≥ 100,000/mcL
• Serum creatinine or calculated Creatinine Clearance: Serum creatinine ≤ 1.5 x ULN or calculated CrCl ≥ 30 mL/min as defined by Cockcroft-Gault equation
• Total Bilirubin: ≤ 1.5 x ULN (≤ 3 x ULN for subjects with documented Gilbert's disease)
• SGOT (AST): ≤ 3 x ULN

You may not qualify if:

• Subjects meeting any of the criteria below may not participate in the study:
• Disease progression on prior checkpoint inhibitor treatment.
• Prior cabozantinib.
• Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before first dose of study treatment.
• Receipt of any type of cytotoxic, biologic or investigational systemic anti-cancer agent within 4 weeks before first dose of study treatment.
• Treatment with abiraterone, apalutamide, or darolutamide within 2 weeks of treatment initiation. Treatment with investigational prostate cancer directed therapy within 4 weeks of treatment initiation. Treatment with enzalutamide within 4 weeks of treatment initiation.
• Receipt of more than 1 line of chemotherapy (including both hormone sensitive and CRPC). First-generation anti-androgen use (such as bicalutamide) will not be tabulated as a line of therapy.
• Administration of a live, attenuated vaccine within 30 days prior to first dose of study treatment.
• Active autoimmune disease or condition requiring prednisone \>10 mg daily (or equivalent). Physiologic replacement is permitted. Topical, ocular, intra-articular steroids or inhaled corticosteroids are permitted.
• Imminent or established spinal cord compression based on clinical and/or imaging findings.
• Radiation therapy within 1 week of study treatment start.
• Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks prior to first dose of study treatment.
• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.
• Malabsorption syndrome.
• Requirement for hemodialysis or peritoneal dialysis.

Sponsors & Collaborators

• Rana McKay, MD: lead
• Exelixis: collaborator
• Bristol-Myers Squibb: collaborator

Study Sites (4)

University of California San Diego

La Jolla, California, 92093, United States

RECRUITING

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

RECRUITING

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

RECRUITING

University of Wisconsin

Madison, Wisconsin, 53705, United States

RECRUITING

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

cabozantinib; Nivolumab

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Rana R. McKay, MD

  University of California, San Diego

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rana R. McKay, MD

CONTACT

858-822-6185; rmckay@ucsd.edu

LeaEtta Hyer

CONTACT

317-634-5842; lhyer@hoosiercancer.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor Investigator

Study Record Dates

• First Submitted: July 18, 2022
• First Posted: August 16, 2022
• Study Start: February 2, 2023
• Primary Completion: April 12, 2026
• Study Completion (Estimated): April 12, 2027
• Last Updated: January 23, 2026

Record last verified: 2026-01

Locations

US (4)