A Trial of Niraparib in Platinum-Sensitive Castration-Resistant Prostate Cancer With DNA Repair Defects

PLATPARP: A Phase II Single-Arm Trial of Niraparib in Platinum-Sensitive Castration-Resistant Prostate Cancer With DNA Repair Defects

This study is designed to evaluate the initial safety and effectiveness of an investigational drug, niraparib, given to patients who have recently received platinum-based chemotherapy for the treatment of prostate cancer. The study enrolls participants with history of advanced prostate cancer that is growing despite standard hormonal therapies, such as androgen-deprivation therapy.

Study Overview

• Status: Completed
• Conditions: Prostate Adenocarcinoma
• Intervention / Treatment: Drug: Niraparib Pill

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Abramson Cancer Center of the University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Histologically or cytologically confirmed diagnosis of prostate adenocarcinoma (mixed histology will be acceptable, but pure small cell histology is to be excluded).
2. ≥ 18 years of age.
3. No prior therapy with PARP inhibitor therapy.
4. Patients must have received at least 9 weeks of platinum-based chemotherapy for the treatment of mCRPC as the proximal treatment regimen prior to study screening. Patients must not have evidence of clinical or radiographic disease progression (per Investigator assessment) and should have adequately recovered from chemotherapy-related toxicities (at least 4 weeks following completion of chemotherapy, with treatment-related toxicities ≤ grade 1 per CTCAE version 5).
5. ECOG performance status of ≤ 2.
6. Documented evidence of a pathogenic or likely pathogenic DNA repair aberration in BRCA1/2, ATM, FANCA, PALB2, CHEK2, HDAC2, or BRIP1 through either somatic or germline testing from a CLIA certified laboratory.
7. Radiographic evidence for metastatic disease. Measureable disease (per RECIST) is not required for enrollment. (i.e. bone-only metastatic disease is permitted).
8. Patients with history of treated brain metastases are eligible if off systemic corticosteroids for at least 2 weeks.
9. Clinical evidence for castration-resistance, with total testosterone < 50 ng/dL. Patients who have not undergone bilateral orchiectomy must plan to continue ongoing androgen deprivation therapy for the duration of the trial therapy.

10. Patients must have adequate organ function, as confirmed by laboratory values obtained ≤ 14 calendar days prior to the first day of study therapy:

    Hematologic: Absolute neutrophil count (ANC) ≥ 1.5 × 109/L, platelet count ≥ 100 × 109/L, and hemoglobin ≥ 9 g/dL (may have been transfused)

    Hepatic: Total bilirubin level ≤ 1.5 × the upper limit of normal (ULN) range and AST and ALT levels ≤ 2.5 × ULN or AST and ALT levels ≤ 5 x ULN (for subjects with documented metastatic disease to the liver). (Note: In subjects with Gilbert's syndrome, if total bilirubin is >1.5 × ULN, measure direct and indirect bilirubin and if direct bilirubin is ≤1.5 × ULN, subject may be eligible)

    Renal: Estimated creatinine clearance ≥ 45 mL/min using Cockcroft Gault formula.

11. Patients must have a projected life expectancy of at least 3 months.

Exclusion Criteria:

1. Prior therapy with a PARP inhibitor.
2. Presence of clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication.
3. Presence of known significant immunodeficiency, as determined by the treating investigator.
4. Presence of clinically significant active infections, as determined by the treating investigator.
5. Known allergy to niraparib or any of its components.
6. Prostate cancer with histologic evidence for pure small cell histology

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Niraparib Arm (only arm); Niraparib 200 mg by mouth daily (2 x 100 mg pills) on a 28 day cycle	Drug: Niraparib Pill; Niraparib 200 mg by mouth daily (2 x 100 mg pills)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
6-Month Radiographic Progression-Free Survival (rPFS6)	Proportion of participants alive without radiographic progression (per PCWG2 criteria), clinical deterioration (as assessed by the investigator), or death from any cause, measured from the start of maintenance niraparib therapy using Kaplan-Meier analysis.	6 months from initiation of maintenance niraparib therapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With PSA50 Response	Number of participants achieving a ≥50% decline in serum PSA from baseline while on maintenance niraparib therapy. Participants with baseline PSA <0.5 ng/mL will be excluded from this analysis.	From baseline until end of treatment, or up to 24 months
Number of Participants With PSA30 Response	Number of participants achieving a ≥30% decline in serum PSA from baseline while on maintenance niraparib therapy. Participants with baseline PSA <0.5 ng/mL will be excluded from this analysis.	From baseline until end of treatment, or up to 24 months
Time to PSA Progression	Time from initiation of maintenance niraparib therapy to the first PSA increase >25% and ≥2 ng/mL from nadir, per PCWG2 criteria. Participants with baseline PSA <0.5 ng/mL were not evaluable. Participants without an event were censored at the last PSA assessment.	From baseline until end of treatment, or up to 24 months
Overall Survival (OS)	Time from initiation of maintenance niraparib therapy to death from any cause, estimated by Kaplan-Meier analysis.	From initiation of maintenance niraparib therapy until death from any cause, up to 36 months

Collaborators and Investigators

• Sponsor: Abramson Cancer Center at Penn Medicine
• Investigators: Principal Investigator: Vivek Narayan, MD, Ambramson Cancer Center of the University of Pennsylvania

Study record dates

Study Major Dates

• Study Start (Actual): October 19, 2020
• Primary Completion (Actual): February 20, 2024
• Study Completion (Actual): February 20, 2024

Study Registration Dates

• First Submitted: February 26, 2020
• First Submitted That Met QC Criteria: February 27, 2020
• First Posted (Actual): February 28, 2020

Study Record Updates

• Last Update Posted (Actual): March 4, 2026
• Last Update Submitted That Met QC Criteria: February 12, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Poly(ADP-ribose) Polymerase Inhibitors; niraparib
• Other Study ID Numbers: UPCC 21819

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Will not need to use IPD

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No