Status:

COMPLETED

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

Lead Sponsor:

Abramson Cancer Center at Penn Medicine

Conditions:

Prostate Adenocarcinoma

Eligibility:

MALE

18+ years

Phase:

PHASE2

Brief Summary

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 treatmen...

Eligibility Criteria

Inclusion

  • Histologically or cytologically confirmed diagnosis of prostate adenocarcinoma (mixed histology will be acceptable, but pure small cell histology is to be excluded).
  • ≥ 18 years of age.
  • No prior therapy with PARP inhibitor therapy.
  • 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).
  • ECOG performance status of ≤ 2.
  • 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.
  • Radiographic evidence for metastatic disease. Measureable disease (per RECIST) is not required for enrollment. (i.e. bone-only metastatic disease is permitted).
  • Patients with history of treated brain metastases are eligible if off systemic corticosteroids for at least 2 weeks.
  • 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.
  • 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.
  • Patients must have a projected life expectancy of at least 3 months.

Exclusion

  • Prior therapy with a PARP inhibitor.
  • 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.
  • Presence of known significant immunodeficiency, as determined by the treating investigator.
  • Presence of clinically significant active infections, as determined by the treating investigator.
  • Known allergy to niraparib or any of its components.
  • Prostate cancer with histologic evidence for pure small cell histology

Key Trial Info

Start Date :

October 19 2020

Trial Type :

INTERVENTIONAL

Allocation :

ACTUAL

End Date :

February 20 2024

Estimated Enrollment :

12 Patients enrolled

Trial Details

Trial ID

NCT04288687

Start Date

October 19 2020

End Date

February 20 2024

Last Update

November 12 2024

Active Locations (1)

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Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, United States, 19104