AtezoCab: A Phase II Study of Cabozantinib in Combination With Atezolizumab in Patients With Metastatic Castration-Resistant Prostate Cancer (mCRPC) With Non-Measurable Disease
Overview
- Phase
- Phase 2
- Intervention
- Atezolizumab
- Conditions
- Castration-Resistant Prostate Carcinoma
- Sponsor
- University of Utah
- Enrollment
- 33
- Locations
- 1
- Primary Endpoint
- Disease control rate
- Status
- Recruiting
- Last Updated
- 12 months ago
Overview
Brief Summary
This phase II trial tests whether cabozantinib and atezolizumab work to shrink tumors in patients with castrate-resistant prostate cancer that had 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 atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving cabozantinib and atezolizumab may kill more tumor cells in patients with metastatic castrate-resistant prostate cancer.
Detailed Description
PRIMARY OBJECTIVE: I. To evaluate the disease control rate in metastatic castration-resistant prostate cancer (mCRPC) patients with non-measurable disease as assessed by Prostate Cancer Working Group 3 (PCWG3)-modified Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 SECONDARY OBJECTIVES: I. To evaluate the efficacy of the combination as measured by prostate-specific antigen (PSA) progression-free survival (PFS). II. To evaluate the efficacy of the combination as measured by PSA 50% response rate. III. To evaluate the efficacy of the combination as measured by radiographic progression-free survival (PFS). IV. To evaluate the efficacy of the combination as measured by overall survival (OS). V. To evaluate the safety of cabozantinib S-malate (cabozantinib) in combination with atezolizumab in patients with mCRPC with non-measurable disease. EXPLORATORY OBJECTIVE: I. To analyze tissue and tumor-based biomarkers to evaluate the mechanisms of treatment activity and resistance. OUTLINE: Patients receive cabozantinib orally (PO) once daily (QD) on days 1-21 and atezolizumab intravenously (IV) over 30-60 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days and then every 3 months until disease progression or start of another therapy.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male subject aged \>= 18 years
- •Histologically or cytologically confirmed prostatic adenocarcinoma without small cell histology
- •Metastatic disease progression after continuous androgen deprivation therapy for hormone sensitive state
- •Patient must have non-measurable disease outside the pelvis (above aortic bifurcation) per RECIST 1.1 criteria. Non-measurable disease can be bone lesions and/or extraskeletal disease
- •Disease progression on or after at least one prior novel hormonal therapy (NHT) (defined as second-generation antiandrogen therapies that include but are not limited to abiraterone acetate, enzalutamide, apalutamide, darolutamide)
- •Eastern Cooperative Oncology Group (ECOG) performance Status =\< 2
- •Effective castration with serum testosterone levels =\< 0.5 ng/mL (=\<1.7 nmol/L)
- •Tumor tissue available (archival or recent tumor biopsy). If no tumor tissue is available, patients can be enrolled after approval from Principal Investigator.
- •Absolute neutrophil count (ANC) \>= 1500/mm\^3 without granulocyte colony-stimulating factor support
- •White blood cell count \>= 2500/uL
Exclusion Criteria
- •Prior chemotherapy in the metastatic castration refractory prostate cancer setting is not allowed (taxane-based in metastatic castration-sensitive disease is allowed)
- •Prior treatment with cabozantinib, CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-a, anti-PD1 and anti-PD-L1 therapeutic antibodies
- •Prior treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 \[IL-2\]) within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment
- •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 other systemic anticancer therapy (including investigational) within 4 weeks before first dose of study treatment
- •Receiving other investigational agents
- •Patients with measurable disease outside the pelvis (above aortic bifurcation) per RECIST 1.1 criteria
- •History of Leptomeningeal disease
- •Uncontrolled tumor-related pain
- •Note: Patients requiring pain medication must be on a stable regimen at study entry
Arms & Interventions
Treatment (cabozantinib, atezolizumab)
Patients receive cabozantinib PO QD on days 1-21 and atezolizumab IV over 30-60 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Intervention: Atezolizumab
Treatment (cabozantinib, atezolizumab)
Patients receive cabozantinib PO QD on days 1-21 and atezolizumab IV over 30-60 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Intervention: Cabozantinib S-malate
Outcomes
Primary Outcomes
Disease control rate
Time Frame: At 24 weeks
Measured per Prostate Cancer Working Group 3 (PCWG3)-modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 with a 95% confidence interval.
Secondary Outcomes
- Progression-free survival (PFS)(From the start date of treatment and the date of first recurrence or death from any cause, assessed up to 3 years after the initiation of therapy)
- Overall survival(From trial initiation and death of any cause, assessed up to 5 years)
- Incidence of adverse events (AEs)(Up to 30 days after completion of study treatment)
- Prostate-specific antigen (PSA) progression-free survival (PFS)(From treatment initiation until documented clinical or radiographic progression or death from any cause, assessed up to 3 years)
- PSA levels(Baseline up to 30 days after completion of study treatment)