Niraparib Before Surgery in Treating Patients With High Risk Localized Prostate Cancer and DNA Damage Response Defects

NCT04030559 | Active Not Recruiting Phase 2 DMC FDA Drug

• 4 other identifiers: 1412676NCI-2019-04365UCDCC#279P30CA093373
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well niraparib, when given before surgery, works in treating patients with high risk prostate cancer that has not spread to other parts of the body (localized) and alterations in deoxyribonucleic acid (DNA) repair pathways. Niraparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Conditions

ATM Gene Mutation; BRCA1 Gene Mutation; BRCA2 Gene Mutation; BRIP1 Gene Mutation; CDK12 Gene Mutation; CHEK1 Gene Mutation; CHEK2 Gene Mutation; DNA Damage Response Gene Mutation; DNA Repair Gene Mutation; FANCA Gene Mutation; FANCD2 Gene Mutation; FANCL Gene Mutation; GEN1 Gene Mutation; NBN Gene Mutation; Prostate Carcinoma; RAD51 Gene Mutation; RAD51C Gene Mutation

Outcome Measures

Primary Outcomes (1)

• Pathologic response rate (pRR)

  The study will assess the impact of neoadjuvant niraparib therapy prior to radical prostatectomy (RP) on pathologic tumor stage, frequency of lymph node metastases and positive margin rates for patients undergoing radical prostatectomy for high-risk, clinically localized prostate cancer with alterations in deoxyribonucleic acid (DNA) repair pathways. Pathologic complete response (PCR) defined as no tumor identified on hematoxylin and eosin (H\&E) stained sections will be assessed; minimal residual disease (MRD) will be defined as tumor clusters limited to \< 5 mm and confined to prostate gland. Exact 95% confidence intervals for pRR and other binary outcomes, adjusted for the two-stage design, will be calculated as described by Koyama and Chen. Response rates will be compared between patients with biallelic and monoallelic loss using Fisher's Exact Test.

  At the time of radical prostatectomy procedure

Secondary Outcomes (1)

• Biochemical prostate specific antigen (PSA) progression free survival

  Up to 5 years

Study Arms (1)

Treatment (niraparib)

EXPERIMENTAL

Patients receive niraparib PO QD on days 1-28. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Following completion of treatment, patients then undergo standard of care surgery.

Drug: Niraparib; Drug: Niraparib Tosylate Monohydrate; Procedure: Radical Prostatectomy

Interventions

Niraparib DRUG

Given PO

Also known as: MK-4827, MK4827

Treatment (niraparib)

Niraparib Tosylate Monohydrate DRUG

Given PO

Also known as: Zejula

Treatment (niraparib)

Radical Prostatectomy PROCEDURE

Undergo standard of care surgery

Also known as: Prostatovesiculectomy

Treatment (niraparib)

Eligibility Criteria

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

You may qualify if:

• Ability to understand and willingness to sign an informed consent form
• Ability to adhere to the study visit schedule and other protocol requirements
• Patients must have histologically or cytologically confirmed prostate cancer that is clinically localized as defined by negative cross-section imaging and/or bone scan, and classified as high or very high risk per National Comprehensive Cancer Network (NCCN) guideline
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 1
• Life expectancy \>= 10 years
• Men who have selected radical prostatectomy as the primary treatment for their prostate cancer
• Must be able to swallow whole capsules
• To avoid risk of drug exposure through the ejaculate, male subjects (even if they have undergone a successful vasectomy) must agree while on study therapy (including during dose interruptions) and for 3 months following the last dose of study drug to:
• Use a condom during sexual activity or practice complete sexual abstinence
• Not donate sperm
• Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L (obtained =\< 14 days of the first study treatment)
• Platelet count \>= 100 x 10\^9/L (obtained =\< 14 days of the first study treatment)
• Hemoglobin \>= 9 g/dL (may have been transfused) (obtained =\< 14 days of the first study treatment)
• Total bilirubin level =\< 1.5 x the upper limit of normal (ULN) range (obtained =\< 14 days of the first study treatment)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels =\< 2.5 x ULN or AST and ALT levels =\< 5 x ULN (for subjects with documented metastatic disease to the liver) (obtained =\< 14 days of the first study treatment)

You may not qualify if:

• Any condition that would prohibit the understanding or rendering of informed consent
• Prior treatment for prostate cancer
• Prior treatment with a PARP inhibitor
• Prior treatment with androgen deprivation therapy (luteinizing hormone-releasing hormone \[LHRH\] agonist/antagonist), antiandrogen (e.g., bicalutamide, nilutamide, enzalutamide, apalutamide), or androgen synthesis inhibitor (e.g., abiraterone, orteronel)
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
• Uncontrolled concomitant disease that in the opinion of the investigator would interfere with the patient's safety or compliance on trial
• Severe infection that in the opinion of the investigator would interfere with the patient's safety or compliance on trial within 4 weeks prior to enrollment
• Known allergies, hypersensitivity, or intolerance to niraparib or its excipients (refer to investigator's brochure)
• Known disorder affecting gastrointestinal absorption
• Corrected QT interval by the Fridericia correction formula (QTcF) on the screening electrocardiography (ECG) \> 450 msec
• Receiving concomitant medications that prolong QTc and are unable to discontinue use while receiving study drug
• History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes)
• Known human immunodeficiency virus (HIV) positive subjects with 1 or more of the following:
• Not receiving antiretroviral therapy
• A change in antiretroviral therapy within 6 months of the start of screening (except if, after consultation with the sponsor, a change is made to avoid a potential drug-drug interaction with the study drug)

Sponsors & Collaborators

• Marc Dall'Era, MD: lead
• National Cancer Institute (NCI): collaborator
• Janssen, LP: collaborator

Study Sites (1)

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

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

Related Links

• Learn more or sign up for the study here!

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

niraparib

Condition Hierarchy (Ancestors)

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

Study Officials

• Marc Dall'Era

  University of California, Davis

  PRINCIPAL INVESTIGATOR

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: Principal Investigator

Study Record Dates

• First Submitted: July 22, 2019
• First Posted: July 24, 2019
• Study Start: February 25, 2020
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: August 26, 2025

Record last verified: 2025-07

Locations

US (1)