RWF C3441021 TALAPRO-2 - A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of TALAZOPARIB with ENZALUTAMIDE in Metastatic Castration-Resistant Prostate Cancer
This study compares rPFS in men with mCRPC treated with talazoparib plus enzalutamide vs. enzalutamide after confirmation of the starting dose of talazoparib in combination with enzalutamide.
• Histologically or cytologically confirmed adenocarcinoma of the prostate withoutsmall cell or signet cell features
• Asymptomatic or mildly symptomatic metastatic castration resistant prostate cancer (mCRPC) (score on BPI-SF Question #3 must be < 4).
• For enrollment into Part 2 only (optional in Part 1): assessment of DDR mutation status
• Consent to a saliva sample collection for a germline comparator unless prohibited by local regulations or ethics committee decision (optional for patients in Part 1).
• Surgically or medically castrated, with serum testosterone ≤ 50 ng/dL (≤ 1.73 nmol/L) at screening.
• Metastatic disease in bone documented on bone scan or in soft tissue documented on CT/MRI scan.
• Progressive disease at study entry in the setting of medical or surgical castration as defined by 1 or more of the following 3 criteria:
• Prostate specific antigen (PSA) progression defined by a minimum of 2 rising PSA values from 3 consecutive assessments with an interval of at least 7 days between assessments..
• Soft tissue disease progression as defined by RECIST 1.1.
• Bone disease progression defined by Prostate Cancer Working Group 3 (PCWG3) with 2 or more new metastatic bone lesions on a whole body radionuclide bone scan.
• Bisphosphonate or denosumab dosage must have been stable for at least 4 weeks before Day 1 (Part 1) or randomization (Part 2) for patients receiving these therapies
• Life expectancy ≥ 12 months as assessed by the investigator.
• Able to swallow the study drug and have no known intolerance to study drugs or excipients.
• Any prior systemic cancer treatment initiated in in the non metastatic CRPC and mCRPC disease state.
• Patients whose only evidence of metastasis is adenopathy below the aortic bifurcation.
• Prior treatment with a PARP inhibitor, cyclophosphamide, or mitoxantrone for prostate cancer.
• Prior treatment with platinum-based chemotherapy within 6 months prior to Day 1 (Part 1) or randomization (Part 2), or any history of disease progression on platinum-based therapy at any time in the past.
• Treatment with cytotoxic chemotherapy, biologic therapy including sipuleucel T (other than approved bone targeting agents and GnRH agonist/antagonist therapy), or radionuclide therapy in the 28 days prior to Day 1 (Part 1) or randomization (Part 2).
• Treatment with any investigational agent within 4 weeks or 5 half-lives of the drug (whichever is longer) before Day 1 (Part 1) or randomization (Part 2).
• Prior treatment with opioids for pain related to either primary prostate cancer or metastasis within 28 days prior to Day 1 (Part 1) or randomization (Part 2) unless no pain related to prostate cancer has been reported in the 28 days prior to Day 1 (Part 1) or randomization (Part 2).
• Clinically significant cardiovascular disease
• Significant renal dysfunction
• Patients enrolled in Part 1 only: Moderate renal impairment at screening.
• Known or suspected brain metastasis or active leptomeningeal disease.
• Symptomatic or impending spinal cord compression or cauda equina syndrome.
• History of another cancer including myelodysplastic syndrome or acute myeloid leukemia, with the exception of uncomplicated nonmelanoma skin cancers, or American Joint Committee on Cancer stage 0 or stage 1 cancer that has a remote probability of recurrence in the opinion of the investigator and the sponsor
• Gastrointestinal disorder affecting absorption.
Brendan Curti, M.D.
- Oncology and Hematology Care Westside
- Providence Cancer Institute Clackamas Clinic
- Providence Cancer Institute Franz Clinic
- Providence Cancer Institute Newberg Clinic