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OncoMatch/Clinical Trials/NCT05498272

Study of Neoadjuvant PARP Inhibition Followed by Radical Prostatectomy in Patients With Unfavorable Intermediate-Risk or High-Risk Prostate Cancer With Select HRR Gene Alterations

Is NCT05498272 recruiting? Yes, currently enrolling (May 2026). This Phase 2 trial studies multiple treatments including Olaparib and LHRH agonist for prostate cancer.

Phase 2RecruitingRana McKay, MDNCT05498272Data as of May 2026

Treatment: Olaparib · LHRH agonistPhase 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.

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Extracted eligibility criteria

Cancer type

Prostate Cancer

Biomarker criteria

Required: BRCA1 germline or somatic gene alteration

Must have evidence of germline or somatic BRCA1/2, PALB2, RAD51B, RAD51C, RAD51D, RAD54L2, BARD1, FANCA, BRIP1, CHEK2, ATM, and CDK12 gene alteration via standard of care CLIA based assay detection.

Required: BRCA2 germline or somatic gene alteration

Must have evidence of germline or somatic BRCA1/2, PALB2, RAD51B, RAD51C, RAD51D, RAD54L2, BARD1, FANCA, BRIP1, CHEK2, ATM, and CDK12 gene alteration via standard of care CLIA based assay detection.

Required: PALB2 germline or somatic gene alteration

Must have evidence of germline or somatic BRCA1/2, PALB2, RAD51B, RAD51C, RAD51D, RAD54L2, BARD1, FANCA, BRIP1, CHEK2, ATM, and CDK12 gene alteration via standard of care CLIA based assay detection.

Required: RAD51B germline or somatic gene alteration

Must have evidence of germline or somatic BRCA1/2, PALB2, RAD51B, RAD51C, RAD51D, RAD54L2, BARD1, FANCA, BRIP1, CHEK2, ATM, and CDK12 gene alteration via standard of care CLIA based assay detection.

Required: RAD51C germline or somatic gene alteration

Must have evidence of germline or somatic BRCA1/2, PALB2, RAD51B, RAD51C, RAD51D, RAD54L2, BARD1, FANCA, BRIP1, CHEK2, ATM, and CDK12 gene alteration via standard of care CLIA based assay detection.

Required: RAD51D germline or somatic gene alteration

Must have evidence of germline or somatic BRCA1/2, PALB2, RAD51B, RAD51C, RAD51D, RAD54L2, BARD1, FANCA, BRIP1, CHEK2, ATM, and CDK12 gene alteration via standard of care CLIA based assay detection.

Required: RAD54L2 germline or somatic gene alteration

Must have evidence of germline or somatic BRCA1/2, PALB2, RAD51B, RAD51C, RAD51D, RAD54L2, BARD1, FANCA, BRIP1, CHEK2, ATM, and CDK12 gene alteration via standard of care CLIA based assay detection.

Required: BARD1 germline or somatic gene alteration

Must have evidence of germline or somatic BRCA1/2, PALB2, RAD51B, RAD51C, RAD51D, RAD54L2, BARD1, FANCA, BRIP1, CHEK2, ATM, and CDK12 gene alteration via standard of care CLIA based assay detection.

Required: FANCA germline or somatic gene alteration

Must have evidence of germline or somatic BRCA1/2, PALB2, RAD51B, RAD51C, RAD51D, RAD54L2, BARD1, FANCA, BRIP1, CHEK2, ATM, and CDK12 gene alteration via standard of care CLIA based assay detection.

Required: BRIP1 germline or somatic gene alteration

Must have evidence of germline or somatic BRCA1/2, PALB2, RAD51B, RAD51C, RAD51D, RAD54L2, BARD1, FANCA, BRIP1, CHEK2, ATM, and CDK12 gene alteration via standard of care CLIA based assay detection.

Required: CHEK2 germline or somatic gene alteration

Must have evidence of germline or somatic BRCA1/2, PALB2, RAD51B, RAD51C, RAD51D, RAD54L2, BARD1, FANCA, BRIP1, CHEK2, ATM, and CDK12 gene alteration via standard of care CLIA based assay detection.

Required: ATM germline or somatic gene alteration

Must have evidence of germline or somatic BRCA1/2, PALB2, RAD51B, RAD51C, RAD51D, RAD54L2, BARD1, FANCA, BRIP1, CHEK2, ATM, and CDK12 gene alteration via standard of care CLIA based assay detection.

Required: CDK12 germline or somatic gene alteration

Must have evidence of germline or somatic BRCA1/2, PALB2, RAD51B, RAD51C, RAD51D, RAD54L2, BARD1, FANCA, BRIP1, CHEK2, ATM, and CDK12 gene alteration via standard of care CLIA based assay detection.

Performance status

ECOG 0–1(Restricted strenuous activity)

Prior therapy

Cannot have received: hormone therapy for prostate cancer (orchiectomy, antiandrogens, enzalutamide, apalutamide, CYP17 inhibitors, abiraterone, TAK-700, galeterone, ketoconazole, estrogens, radiation therapy)

Exception: Prior bicalutamide allowed if < 4 weeks and 2 week washout; LHRH agonist/antagonist allowed if begun within 4 weeks; prior 5-alpha reductase inhibitors allowed with 2 week washout

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.

Cannot have received: PARP inhibitor

Prior treatment with a PARP inhibitor.

Lab requirements

Blood counts

White blood cell count ≥ 3,000/mcL; Absolute neutrophil count ≥ 1,500/mcL; Hemoglobin ≥ 10 g/dL with no transfusion support in the past 28 days; Platelets ≥ 100,000/mcL

Kidney function

Calculated creatinine clearance ≥ 51 mL/min based on Cockcroft-Gault formula or 24 hour urine

Liver function

Aspartate aminotransferase, alanine aminotransferase ≤ 2.5×ULN, and total bilirubin ≤ 1.5 x Institutional upper limit of normal

Demonstrate adequate organ function as defined below. All screening labs to be obtained within 28 days prior to registration.

Structured fields extracted by AI. May contain errors — verify against the official protocol.

US trial sites

  • University of California San Diego - Moores Cancer Center · La Jolla, California
  • Johns Hopkins Sidney Kimmel Comprehensive Cancer Center · Baltimore, Maryland
  • Columbia University Irving Medical Center · New York, New York
  • Memorial Sloan Kettering Cancer Center · New York, New York
  • University of Cincinnati · Cincinnati, Ohio

Showing up to 5 US sites. See all sites on ClinicalTrials.gov →

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