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).
Single group
Olaparib
Drug300 mg orally twice a day (D1-D30) for 6 Cycles (30 day Cycles)
LHRH agonist
DrugTotal duration of therapy will be for 180 days with use of agent as per institutional standards
Pathological Complete Response (pCR) rate
Assess pCR rate. pCR will be defined as no residual disease in the RP specimen by blinded central pathology review.
Minimal Residual Disease (MRD) rate
Assess the MRD rate. MRD will be defined as residual tumor focus in the RP specimen measuring ≤ 5 mm by blinded central pathology review.
Evaluate changes in Prostate specific antigen (PSA)
PSA kinetics will include nadir value, achieving nadir PSA \< 0.2 ng/mL, achieving 50% or achieving 90% decrease in PSA from baseline, and time to PSA nadir.
Surgical pathologic outcomes at RP
Evaluate surgical pathologic outcomes at RP. At the time of RP, pathologic specimens will be assessed for frequency of positive surgical margins, extracapsular extension, positive seminal vesicles, and positive lymph nodes.
Residual Cancer Burden (RCB) at RP
Evaluate RCB at RP. Residual cancer burden will be determined as the tumor volume x tumor cellularity.
Event Free Survival (EFS)
Evaluate EFS. EFS will be defined as the time from the date of treatment initiation to the date of first evidence of disease progression (defined below) or death from any causes, censored at the date of last disease follow-up (either PSA or imaging test): * Biochemical failure (defined as a serum PSA ≥0.1 ng/mL, which is confirmed by a second determination with a PSA ≥0.1 ng/mL). * Any new evidence of metastatic disease visualized on radiographic imaging (including bone scan, CT, MRI, or positron-emission tomography). * Any new evidence of local recurrence visualized on radiographic imaging (including bone scan, CT, MRI, or positron-emission tomography).
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Rana McKay, MD
Lead sponsor
Hoosier Cancer Research Network
Sponsor institution
AstraZeneca
Collaborator
University of California, San Diego
Collaborator
