RWF_C3441021 TALAPRO-2

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.

Inclusion Criteria:
• 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.

Exclusion Criteria:
• 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.
Phase III
Brendan Curti, M.D.
  • Oncology and Hematology Care Westside
  • Providence Cancer Institute Clackamas Clinic
  • Providence Cancer Institute Franz Clinic
  • Providence Cancer Institute Newberg Clinic