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

NCT05498272 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: HCRN GU20-436
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 6

Brief Summary

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

BRCA1 Mutation; BRCA2 Mutation; Prostatic Adenocarcinoma; Prostate Cancer; High-Risk Cancer

Outcome Measures

Primary Outcomes (2)

• 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.

  4 years

• 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.

  4 years

Secondary Outcomes (10)

• Evaluate changes in Prostate specific antigen (PSA)

  4 years

• Surgical pathologic outcomes at RP

  During surgery

• Residual Cancer Burden (RCB) at RP

  During surgery

• Event Free Survival (EFS)

  4 years

• Treatment Free Survival post RP

  4 years

Study Arms (1)

Investigational Group

EXPERIMENTAL

300 mg of olaparib taken orally twice a day for 6 cycles (approximately 6 months). There are 30 days in a cycle. Olaparib will be taken with an LHRH agonist (leuprolide, triptorelin, or goserlin). This choice of therapy will be taken for a total of 180 days per institutional standards. After 6 cycles of neoadjuvant therapy, patients will undergo a radical prostatectomy (RP). After RP, patients will be followed for testosterone recovery and PSA progression.

Drug: Olaparib; Drug: LHRH agonist

Interventions

Olaparib DRUG

300 mg orally twice a day (D1-D30) for 6 Cycles (30 day Cycles)

Also known as: Lynparza

Investigational Group

LHRH agonist DRUG

Total duration of therapy will be for 180 days with use of agent as per institutional standards

Also known as: Goserelin, Triptorelin, Leuprolide

Investigational Group

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Must have 3 core biopsies involved with cancer (a minimum of 6 core biopsies must be obtained). Prostate biopsy must be within 7 months from registration. Less than 3 core biopsies are allowed if the patient has \>1 cm or T3 disease on magnetic resonance imaging (MRI).
• Localized unfavorable intermediate or high-risk prostate cancer patients. Patients must have at least one of the following features:
• Gleason ≥ 4+3 (grade group 3, 4, 5) OR
• PSA \> 20 ng/dL OR
• T3 disease NOTE: Patients with intraductal carcinoma are eligible independent of Gleason score, PSA and T stage.
• 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. Testing will be confirmed centrally but results of central testing not required for enrollment.
• No evidence of metastatic disease as determined by radionuclide bone scan and CT/MRI. Lymph nodes must be less than 20 mm in the short (transverse) axis.
• Participants must be candidates for RP and considered surgically resectable by urologic evaluation.
• ECOG Performance Status of 0-1 within 28 days prior to registration.
• Demonstrate adequate organ function as defined below. All screening labs to be obtained within 28 days prior to registration.
• White blood cell count ≥ 3,000/mcL

You may not qualify if:

• Subjects meeting any of the criteria below may not participate in the study:
• 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.
• Clinically significant acute infection requiring systemic antibacterial, antifungal, or antiviral therapy including:
• tuberculosis (clinical evaluation that includes clinical history, physical examination, and radiographic findings, and TB testing in line with local practice).
• Known active hepatitis infection, positive hepatitis C antibody, hepatitis B virus surface antigen or hepatitis B virus core antibody at screening. Testing is not required unless there was a prior known positive hepatitis B or C test or hepatitis is suspected at screening. Active hepatitis B virus (HBV) is defined by a known positive HBV surface antigen (HBsAg) result. For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
• Known to have tested positive for human immunodeficiency virus (HIV) unless currently on effective anti-retroviral therapy with an undetectable viral load within 6 months.
• Severe hepatic impairment (Child-Pugh Class C).
• Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication.
• Pre-existing condition that warrants long-term corticosteroid use greater than the equivalent of 10 mg prednisone daily. Physiologic replacement is permitted. Topical, intra-articular steroids or inhaled corticosteroids are permitted.
• Active cardiac disease, defined as:
• Myocardial infarction within 6 months of study treatment.
• Uncontrolled angina within 3 months of study treatment.
• Congestive heart failure New York Heart Association (NYHA) class 3 or 4, or subjects with history of congestive heart failure NYHA class 3 or 4 in the past, or history of anthracycline or anthracenedione (mitoxantrone) treatment, unless an echocardiogram performed within 3 months of the screening visit results in a left ventricular ejection fraction that is ≥ 45%.

Sponsors & Collaborators

• Rana McKay, MD: lead
• AstraZeneca: collaborator
• University of California, San Diego: collaborator

Study Sites (6)

University of California San Diego - Moores Cancer Center

La Jolla, California, 92093, United States

RECRUITING

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21287, United States

RECRUITING

Columbia University Irving Medical Center

New York, New York, 10032, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

University of Cincinnati

Cincinnati, Ohio, 45229, United States

RECRUITING

Penn Medicine Abramson Cancer Center

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Related Publications (1)

• Montgomery B, Mostaghel EA. Neoadjuvant Therapy Prior to Prostatectomy: Is the Glass Half Full? Eur Urol. 2023 Jun;83(6):519-520. doi: 10.1016/j.eururo.2023.01.021. Epub 2023 Jan 27. No abstract available.

  PMID: 36710203 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

olaparib; Gonadotropin-Releasing Hormone; Goserelin; Triptorelin Pamoate; Leuprolide

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Study Officials

• Rana R. McKay, MD

  University of California, San Diego

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rana R. McKay, MD

CONTACT

858-822-6185; rmckay@ucsd.edu

Amber Ryba

CONTACT

317-634-5842; aryba@hoosiercancer.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor Investigator

Study Record Dates

• First Submitted: July 18, 2022
• First Posted: August 12, 2022
• Study Start: February 1, 2023
• Primary Completion: March 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: January 23, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)