Phase II Trial of Zanzalitinib in Patients With Metastatic Castration Resistant Prostate Cancer

Starting soon · Phase 2

Conditions studied: Metastatic Castration-resistant Prostate Cancer

In brief

This research study is for people with metastatic castrate-resistant prostate cancer (mCRPC). Zanzalintinib is a new drug that shows activity in mCRPC with soft tissue or visceral metastases who have progressed on prior treatment. Participants can stay in the research for up to 24 months as long as they experience clinical benefit from it. The purpose of this study is to learn if Zanzalinitib is effective in treating metastatic castrate-resistant prostate cancer.

Key facts

Study ID

NCT07608718

Run by

Pedro Barata, MD, MSc

People needed

19

Starts

2026-09-01

Expected to finish

2030-05-01

Last updated by the study team

2026-05-27

Who can join

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

You may qualify if…

• Participants must have histologically or cytologically confirmed metastatic castrate-resistant prostate cancer. Adenocarcinoma of prostate must be primary histology, but neuroendocrine features are allowed as long as <50% neuroendocrine histology. Tissue is not mandatory, but a pathologic report is required at time of participant enrollment.
• Participants must have evidence of metastatic disease in soft tissue or visceral disease on conventional scans including CT and bone scans
• Participants must have previously been treated with an ARPI (abiraterone, enzalutamide, apalutamide, darolutamide). Prior exposure to 1 line of taxane-based chemotherapy (docetaxel) is allowed.
• Age ≥ 18 years.
• Karnofsky Performance status ≥ 60%
• Participants must have adequate organ and marrow function, based upon meeting all the following laboratory criteria within 14 days before first dose of study treatment as defined below:
• Absolute neutrophil count (ANC) ≥ 1500/mm3 (≥ 1.5 GI/L) without granulocyte colony-stimulating factor support within 2 weeks of screening laboratory sample collection.
• Platelets ≥ 100,000/mm3 (≥ 100 GI/L) without transfusion within 2 weeks of screening laboratory sample collection.
• Hemoglobin ≥ 9 g/dL (≥ 90 g/L) without transfusion within 2 weeks prior to screening laboratory sample collection.
• International Normalized Ratio (INR) ≤ 1.5 and activated partial thromboplastin time (aPTT) ≤ 1.2 x upper limit of normal (ULN).
• Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) ≤ 3 x ULN. For participants with documented bone metastasis ALP ≤ 5 x ULN. For participants with CRPC and bone metastasis ALP ≤ 10 x ULN if predominantly bone-specific ALP.
• Total bilirubin ≤ 1.5 x ULN (for participants with Gilbert's disease ≤ 3 x ULN).
• Serum creatinine ≤ 1.5 x ULN or calculated creatinine clearance ≥ 40 mL/min (≥ 0.67 mL/sec) using the Cockcroft Gault equation.
• Urine protein-to-creatinine ratio (UPCR) ≤ 1 mg/mg (≤ 113.2 mg/mmol) creatinine.
• Recovery to baseline or ≤ Grade 1 severity (CTCAE v5) from adverse events (AEs), including immune-related adverse events (irAEs), related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy (eg, physiological replacement of corticosteroid). Low-grade or controlled toxicities such as alopecia, ≤ Grade 2 hypomagnesemia, ≤ Grade 2 neuropathy are permitted)
• Participants must be capable of understanding and complying with the protocol requirements and must have signed the informed consent document.
• Sexually active fertile participants and their partners must agree to use highly effective method of contraception (defined in Appendix III) during the course of the study and for the following durations after the last dose of treatment (whichever is later). An additional contraceptive method, such as a barrier method (eg, condom), is required. In addition, men must agree not to donate sperm and women must agree not to donate eggs (ova, oocyte) for the purpose of reproduction during these same periods:
• through 186 days after the last dose of zanzalintinib for women of childbearing potential (WOCBP) or through 96 days after the last dose of zanzalintinib for men

You may not qualify if…

• Evidence of hormone-sensitive prostate cancer (HSPC).
• Evidence of small cell prostate cancer.
• Prior treatment with any TKI (including zanzalintinib)
• 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 2 weeks before first dose of study treatment.
• The antiandrogen abiraterone is permitted up to 1 week prior to first dose of study treatment. Concomitant use of megestrol acetate or leuprolide is permitted. Other types of hormonal therapies with similar use require prior approval from the Principal Investigator.
• Another malignancy that requires active therapy and in the opinion of the Investigator would interfere with monitoring of radiologic assessments of response to Investigational Product, within 2 years before first dose of study treatment, except for superficial skin cancers, or localized, low-grade tumors deemed cured and not treated with systemic therapy.
• Participants with BRCA-mutated mCRPC who have not previously received a PARP inhibitor
• Participants with MSI-H mCRPC who have not previously received pembrolizumab or another immune-checkpoint inhibitor for treatment of MSI-H mCRPC
• Radiation therapy for bone metastasis within 2 weeks, 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. Participants with clinically relevant ongoing complications from prior radiation therapy are not eligible.
• Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks before first dose of study treatment. Note: Eligible participants must be neurologically asymptomatic and without corticosteroid treatment at the time of enrollment.
• Base of skull lesions without definitive evidence of dural or brain parenchymal involvement are allowed.
• Concomitant anticoagulation with oral anticoagulants (eg, warfarin, direct thrombin inhibitors ) and platelet inhibitors (eg, clopidogrel).
• Allowed anticoagulants are the following:
• Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH).
• Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban in participants 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.
• Note: Participants must have discontinued oral anticoagulants within 3 days or 5 half-lives prior to first dose of study treatment, whichever is longer.
• The participant has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
• Unstable or deteriorating cardiovascular disorders:
• Congestive heart failure New York Heart Association Class 3 or 4, class 2 or higher, unstable angina pectoris, new-onset angina, serious cardiac arrhythmias (eg, ventricular flutter, ventricular fibrillation, Torsades de pointes).
• Uncontrolled hypertension defined as sustained blood pressure (BP) > 140 mm Hg systolic or > 90 mm Hg diastolic despite optimal antihypertensive treatment.
• Stroke (including transient ischemic attack [TIA]), myocardial infarction, or other clinically significant arterial thrombotic and/or ischemic event within 6 months before first dose of study treatment.
• Pulmonary embolism (PE) or deep vein thrombosis (DVT) or prior clinically significant venous events within 3 months before first dose of study treatment.
• Note: Participants with a diagnosis of DVT within 6 months are allowed if asymptomatic and stable at screening and 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.
• Note: Participants who don't require prior anticoagulation therapy may be eligible but must be discussed and approved by the Principal Investigator.

Where it is running

• University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center — Cleveland, Ohio, United States

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.