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

NCT07608718 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: CASE6825
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Metastatic Castration-resistant Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• Radiographic progression free survival (rPFS) at 6 months

  rPFS is defined as the duration of time from start of treatment to time of progression

  6 months

Secondary Outcomes (5)

• Prostate specific antigen (PSA) response

  6 months

• Time to next systemic treatment

  24 months

• Median progression free survival

  24 months

• Overall Survival (OS)

  24 months

• Objective Response Rate (ORR)

  24 months

Study Arms (1)

Zanzalintiniib

EXPERIMENTAL

Single-arm phase 2 trial of patients with mCRPC (metastatic castration-resistant prostate cancer). About 24 participants will be enrolled in the trial, 9 will initially be enrolled and if 3 participants are still alive and progression-free at 6 months, 15 more participants will be added. 1 cycle is 28 days. If a participant does not complete at least one cycle, the participant will be replaced. Participants who complete one cycle will not be replaced.

Drug: Zanzalintinib

Interventions

Zanzalintinib DRUG

60mg zanzalinitib will be given daily starting on Cycle 1 Day 1 until disease progression or unacceptable toxicity

Zanzalintiniib

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Men and members of all races and ethnic groups are eligible for this trial.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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)

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).

Sponsors & Collaborators

• Pedro Barata, MD, MSc: lead

Study Sites (1)

University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

Cleveland, Ohio, 44106, United States

Location

Study Officials

• Pedro Barata, MD, MSc

  University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Pedro Barata, MD, MSc

CONTACT

216-262-1214; Pedro.Barata@UHhospitals.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: Principal Investigator

Study Record Dates

• First Submitted: May 20, 2026
• First Posted: May 27, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): May 1, 2029
• Study Completion (Estimated): May 1, 2030
• Last Updated: May 27, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data included in the peer-reviewed publication will be publicly available indefinitely. No raw data will be shared
• Access Criteria: A peer-reviewed publication will be made available according to the publishing journal's specifications. UH personnel will not share study data apart that which has been published publicly.

Locations

US (1)