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

  • STATUS
    Recruiting
  • End date
    Feb 1, 2025
  • participants needed
    30
  • sponsor
    University of California, Davis
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Updated on 21 March 2022
See if I qualify
platelet count
vasectomy
prostatectomy
cancer
absolute neutrophil count
tumor cells
bone scan
palb2
fancl
dna damage
rad51c
niraparib

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.

Description

PRIMARY OBJECTIVES:

I. To assess the impact of neoadjuvant niraparib tosylate monohydrate (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 DNA repair pathways.

SECONDARY OBJECTIVE:

I. To assess 5-year biochemical recurrence in subjects with high-risk prostate cancer and DNA-damage response defects after prostatectomy.

OUTLINE

Patients receive niraparib orally (PO) once daily (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.

After completion of study treatment, patients are followed up at 30 days, every 3 months for 2 years, and then every 6 months for up to 3 years.

Details
Condition 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
Treatment Niraparib, Radical Prostatectomy, Niraparib Tosylate Monohydrate
Clinical Study IdentifierNCT04030559
SponsorUniversity of California, Davis
Last Modified on21 March 2022

Eligibility

 Yes No Not Sure

Inclusion Criteria

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 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
Prostate cancer tumors with alterations in key DNA repair genes identified on Foundation One assay. This will include at least one alteration in a gene involved in DNA repair primarily through the homologous recombination pathway including BRCA1/2, ATM, CDK12, CHEK1/2 FANCA, FANCD2, FANCL, GEN1, NBN, PALB2, RAD51, RAD51c, and BRIP1. Mutations will be selected that are known or likely pathogenic. Mean allele frequencies will be assessed to estimate mono versus biallelic loss of function. Patients with biallelic deletions or mutations will be prioritized for inclusion to make up at least 30% of the enrollment (i.e., 10 patients) to gauge response in this group over monoallelic loss. Final inclusion will be determined by the principal investigator
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)
International normalized ratio (INR) and activated partial thromboplastin time (aPTT) =< 1.5 x ULN (for patients on anticoagulation they must be receiving a stable dose for at least 1 week prior to randomization) (obtained =< 14 days of the first study treatment)
Creatinine clearance > 30 mL/min by Cockcroft-Gault formula (or local institutional standard method) (obtained =< 14 days of the first study treatment)

Exclusion Criteria

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)
Receiving antiretroviral therapy that may interfere with the study drug (consult the principal investigator [PI] for review of medication prior to enrollment)
CD4 count < 350 at screening
An acquired immunodeficiency syndrome-defining opportunistic infection within 6 months of the start of screening
Clear my responses
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