Phase 2 open-label, single-arm clinical trial evaluating the efficacy and safety of neoadjuvant olaparib + LHRH agonist administered for 6 months prior to radical prostatectomy (RP) in men with unfavorable intermediate-risk or high-risk localized prostate cancer. All patients must have confirmed germline or somatic select HRR alterations. Germline and somatic mutation testing will be performed as part of commercially available CLIA assays and will be validated on a uniform platform centrally all patients retrospectively.
Eligible patients will receive treatment with olaparib + LHRH agonist. Following 6 months of therapy, patients will undergo RP with mandatory lymph node dissection. The lymph node dissection template will be at the discretion of the treating urologist. RP specimens will undergo pathology blinded independent central review. Following RP, patients will be followed for testosterone recovery and PSA progression.
Written informed consent and HIPAA authorization for release of personal health information prior to registration.
Age ≥ 18 years at the time of consent.
T stage 1-3 prostatic adenocarcinoma per AJCC staging manual Ed8.
Histologically confirmed adenocarcinoma of the prostate without histological variants comprising >50% of the sample. Patients with intraductal carcinoma are eligible.
Active infection requiring systemic therapy.
Prior treatments not allowed: hormone therapy for prostate cancer including orchiectomy, antiandrogens (including first-generation antiandrogens, enzalutamide, apalutamide and others), CYP17 inhibitors (including abiraterone, TAK-700, galeterone, ketoconazole, and others), estrogens and radiation therapy. Prior bicalutamide is allowed if taken for < 4 weeks prior to registration and there is a washout period of 2 weeks prior to the initiation of study treatment. LHRH agonist/antagonist therapy is allowed if begun within 4 weeks of registration. Prior 5-alpha reductase inhibitors are allowed but require a washout period of 2 weeks to initiation of study treatment.
Prior treatment with a PARP inhibitor.
tuberculosis (clinical evaluation that includes clinical history, physical examination, and radiographic findings, and TB testing in line with local practice).
Rana McKay, MD
Lead sponsor
Hoosier Cancer Research Network
Sponsor institution
AstraZeneca
Collaborator
University of California, San Diego
Collaborator