Study of Cabozantinib and Nivolumab in Metastatic Castration Resistant Prostate Cancer

• Status: Not yet recruiting
• Trial end date: 2024-04-12
• Target enrollment: 0
• Participant gender: Male

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).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Rana McKay, MD
• Collaborators: Bristol-Myers Squibb; Exelixis
• Treatments: Nivolumab

Criteria

Inclusion Criteria:

Subjects must meet all of the following applicable inclusion criteria to participate in this study:

• 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.

• 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.

• 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 within 7 days of study treatment are permitted)

• Platelet count: ≥ 100,000/mcL

• Serum creatinine or calculated Creatinine Clearance: Serum creatinine ≤ 1.5 x ULN or calculated CrCl ≥ 40 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

• SGPT (ALT): ≤ 3 x ULN

• Alkaline Phosphatase (ALP) : ≤ 5 x ULN with documented bone metastases

• Serum Albumin: ≥ 2.8 g/dL

• Urine protein/creatinine ratio (UPCR): ≤ 1 mg/mg (≤ 113.2 mg/mmol), or 24-h urine protein ≤ 1 g

• Subjects must agree to use a medically acceptable method of birth as outlined in the protocol

• HIV-positive with negative viral loads on stable antiretroviral regimen will be considered eligible. Subjects must have CD4 count > 350.

Exclusion Criteria:

Subjects meeting any of the criteria below may not participate in the study:

• Small cell or neuroendocrine component or histology.

• Prior cabozantinib or checkpoint inhibitor.

• 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.

• Prior treatment with radium-223.

• Receipt of more than 2 lines of therapy for CRPC. 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.

• History of solid organ or allogenic stem cell transplant.

• Active hepatitis B/C or positive TB test with active mycobacterial infection requiring systemic treatment.

• Active treatment (within 5 days of registration) with coumarin agents (e.g., warfarin), direct thrombin inhibitors (e.g., dabigatran), direct factor Xa inhibitor betrixaban, or platelet inhibitors (e.g., clopidogrel).

• The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:

• Cardiovascular disorders.

• Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation.

• Major surgery (e.g., laparoscopic nephrectomy, GI surgery, removal or biopsy of brain metastasis) within 2 weeks before first dose of study treatment. Minor surgeries within 10 days before first dose of study treatment. Subjects must have complete wound healing from major surgery or minor surgery before first dose of study treatment. Subjects with clinically relevant ongoing complications from prior surgery are not eligible.

• Any other active malignancy at time of first dose of study treatment or diagnosis of another malignancy within 3 years prior to first dose of study treatment that requires active treatment.

• Known allergy to any of the compounds under investigation.

• Inability to swallow tablets.