Cabozantinib and Atezolizumab for the Treatment of Metastatic Castration-Resistant Prostate Cancer

Recruiting now · Phase 2

Conditions studied: Castration-Resistant Prostate Carcinoma, Metastatic Prostate Adenocarcinoma, Stage IV Prostate Cancer AJCC v8, Stage IVA Prostate Cancer AJCC v8, Stage IVB Prostate Cancer AJCC v8

In brief

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.

Key facts

Study ID

NCT05168618

Run by

University of Utah

People needed

33

Starts

2022-03-29

Expected to finish

2027-01-01

Last updated by the study team

2026-06-05

Who can join

Age: 18 and older. Sex: male. Healthy volunteers: not accepted.

You may qualify if…

• 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
• Lymphocyte count >= 0.5 x 10\^9/L (500/uL)
• Platelet count >= 100,000/mm\^3 without transfusion in the 2 weeks prior to cycle 1 day 1 (C1D1)
• Hemoglobin >= 9 g/dL
• Serum albumin >= 2.5 g/dl
• For patients not receiving therapeutic anticoagulation: prothrombin time (PT)/International normalized ratio (INR) or partial thromboplastin time (PTT) test < 1.5 x institutional upper limit of normal (ULN). For patients receiving therapeutic anticoagulation: stable anticoagulant regimen as determined by Investigator
• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN). For subjects with Gilbert's disease =< 3 x institutional ULN
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 × institutional ULN
• Subjects with liver metastases will be allowed to enroll with AST and ALT levels =< 5 x institutional ULN
• Alkaline phosphatase (ALP) =< 3 × institutional ULN. Patients with documented liver or bone metastases: ALP =< 5 x institutional ULN
• Serum creatinine =< 1.5 x institutional ULN or calculated creatinine clearance >= 40 mL/min by Cockcroft-Gault formula
• Urine protein/creatinine ration (UPCR) =< 1mg/mg (=< 113.2 mg/mmol), or 24-hour (h) urine protein =< 1 g
• Sexually active fertile subjects and their partners must agree to use medically accepted methods of contraception (e.g., barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the course of the study and for 5 months after the last dose of study treatment
• Male subjects must agree to use a condom during intercourse for the duration of study therapy
• Recovery to baseline or =< grade 1 Common Terminology Criteria for Adverse Events (CTCAE) v5.0 from toxicities related to any prior cancer therapy, unless considered clinically not significant by the treating investigator and/or stable on supportive therapy
• Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines

You may not qualify if…

• 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
• Symptomatic lesions (e.g., bone metastases or metastases causing nerve impingement) amenable to palliative radiotherapy should be treated prior to enrollment. Patients should be recovered from the effects of radiation
• Asymptomatic metastatic lesions that would likely cause functional deficits or intractable pain with further growth (e.g., epidural metastasis that is not currently associated with spinal cord compression) should be considered for loco-regional therapy if appropriate prior to enrollment
• Radiation therapy for bone metastasis within 2 weeks or any other radiation therapy within 4 weeks before first dose of study treatment. Systemic treatment with radionuclides within 6 weeks before first dose of study treatment. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible
• Major surgery (e.g., laparoscopic nephrectomy, gastrointestinal (GI) surgery, removal or biopsy of brain metastasis) within 4 weeks before first dose of study treatment or anticipation of need for a major surgical procedure during the study. 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, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5-year overall survival [OS] rate > 90%), such as locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the breast
• Known brain metastases or cranial epidural disease
• Note: Brain metastases or cranial epidural disease adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks before the first dose of study treatment after radiotherapy or at least 4 weeks prior to the first dose of study treatment after major surgery (e.g. removal or biopsy of brain metastasis) will be allowed on trial. Subjects must have complete wound healing from major surgery or minor surgery before first dose of study treatment. Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of the first dose of study treatment
• Concomitant anticoagulation with coumarin agents (e.g., warfarin), direct thrombin inhibitors (e.g., dabigatran), direct factor Xa inhibitor betrixaban, or platelet inhibitors (e.g., clopidogrel). Allowed anticoagulants are the following:
• Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines), low-dose low molecular weight heparins (LMWH), or prophylactic dose of anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban.
• Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban in subjects without known brain metastases who are on a stable dose of the anticoagulant for at least 1 week before first dose of study treatment without clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor
• Administration of a live, attenuated vaccine (e.g., FluMist) within 30 days before first dose of any study treatment and for 5 months after the last dose of any study treatment
• Current evidence of uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
• Cardiovascular disorders:
• Congestive heart failure New York Heart Association Class II, III or IV, unstable angina pectoris, serious unstable cardiac arrhythmias
• Stroke (including transient ischemic attack [TIA]), myocardial infarction (MI), other ischemic events, or thromboembolic event (e.g., deep venous thrombosis, pulmonary embolism) within 6 months before the first dose of study treatment

Where it is running

• Huntsman Cancer Institute/University of Utah — Salt Lake City, Utah, United States (enrolling)

Full record on ClinicalTrials.gov

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