Actively Recruiting

Phase 2
Age: 18Years +
MALE
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

Led by Rana McKay, MD · Updated on 2026-01-23

32

Participants Needed

6

Research Sites

199 weeks

Total Duration

On this page

Sponsors

R

Rana McKay, MD

Lead Sponsor

A

AstraZeneca

Collaborating Sponsor

AI-Summary

What this Trial Is About

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.

CONDITIONS

Official Title

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

Who Can Participate

Age: 18Years +
MALE

Eligibility Criteria

Eligible

You may qualify if you...

  • Written informed consent and HIPAA authorization prior to registration
  • Male aged 18 years or older
  • Prostatic adenocarcinoma T stage 1-3 confirmed by pathology
  • At least 3 prostate biopsy cores involved with cancer (minimum 6 cores taken)
  • Localized unfavorable intermediate or high-risk prostate cancer with Gleason score  4+3, or PSA > 20 ng/dL, or T3 disease
  • Evidence of germline or somatic alterations in BRCA1/2, PALB2, RAD51B, RAD51C, RAD51D, RAD54L2, BARD1, FANCA, BRIP1, CHEK2, ATM, or CDK12 genes by CLIA assay
  • No metastatic disease by bone scan and CT/MRI; lymph nodes < 20 mm in short axis
  • Candidate for radical prostatectomy and considered surgically resectable
  • ECOG performance status 0-1 within 28 days prior to registration
  • Adequate organ function including blood counts, liver enzymes, and kidney function within 28 days prior to registration
  • Life expectancy of at least 16 weeks
  • Use of condom plus spermicide during and for 3 months after treatment when having sexual intercourse with a woman of childbearing potential
  • Ability to understand and comply with study procedures
Not Eligible

You will not qualify if you...

  • Active infection requiring systemic therapy
  • Prior hormone therapy for prostate cancer (except short-term bicalutamide with washout or recent LHRH agonist/antagonist therapy)
  • Prior treatment with any PARP inhibitor
  • Clinically significant acute infections including tuberculosis or active hepatitis
  • Known HIV infection unless on effective therapy with undetectable viral load
  • Severe liver impairment (Child-Pugh Class C)
  • Inability to swallow oral medications or gastrointestinal disorders affecting absorption
  • Long-term corticosteroid use above prednisone 10 mg daily (physiologic replacement allowed)
  • Active cardiac disease or recent significant cardiac events
  • Uncontrolled cardiac conditions or congenital long QT syndrome
  • History of another cancer under active treatment or visible on scans
  • Major surgery within 4 weeks before treatment start
  • Recent investigational drug use within 28 days
  • Persistent toxicities grade > 2 from previous cancer therapy
  • Myelodysplastic syndrome or acute myeloid leukemia or suggestive features
  • Poor medical risk due to serious uncontrolled illness or infection
  • Recent chemotherapy or radiotherapy within 3 weeks prior to treatment
  • Use of strong CYP3A inhibitors or inducers without proper washout
  • Previous allogenic bone marrow or double umbilical cord blood transplant
  • Whole blood transfusions within 120 days prior to study
  • Known allergy to olaparib or its components

AI-Screening

AI-Powered Screening

Complete this quick 3-step screening to check your eligibility

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Trial Site Locations

Total: 6 locations

1

University of California San Diego - Moores Cancer Center

La Jolla, California, United States, 92093

Actively Recruiting

2

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, United States, 21287

Actively Recruiting

3

Columbia University Irving Medical Center

New York, New York, United States, 10032

Actively Recruiting

4

Memorial Sloan Kettering Cancer Center

New York, New York, United States, 10065

Actively Recruiting

5

University of Cincinnati

Cincinnati, Ohio, United States, 45229

Actively Recruiting

6

Penn Medicine Abramson Cancer Center

Philadelphia, Pennsylvania, United States, 19104

Actively Recruiting

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Research Team

R

Rana R. McKay, MD

CONTACT

A

Amber Ryba

CONTACT

How is the study designed?

Study Type

INTERVENTIONAL

Masking

NONE

Allocation

NA

Model

SINGLE_GROUP

Primary Purpose

TREATMENT

Number of Arms

1

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