Clinical Trials /

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

NCT04288687

Description:

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.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: UPCC 21819
  • NCT ID: NCT04288687

Conditions

  • Prostate Adenocarcinoma

Interventions

DrugSynonymsArms
Niraparib PillNiraparib Arm (only arm)

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Niraparib Arm (only arm)OtherNiraparib 200 mg by mouth daily (2 x 100 mg pills) on a 28 day cycle
  • Niraparib Pill

Eligibility Criteria

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:rPFS6
Time Frame:6 months
Safety Issue:
Description:Assessment of the 6-month radiographic progression-free survival (rPFS) rate in patients with platinum-sensitive mCRPC harboring germline or somatic DNA repair defects as determined by Kaplan-Meier analysis.

Secondary Outcome Measures

Measure:PSA30
Time Frame:3 months
Safety Issue:
Description:Proportion of patients achieving a ≥30% decline in PSA following the initiation of niraparib maintenance therapy
Measure:PSA50
Time Frame:3 months
Safety Issue:
Description:Proportion of patients achieving a ≥50% decline in PSA following the initiation of niraparib maintenance therapy
Measure:Time to PSA progression
Time Frame:6 months
Safety Issue:
Description:Time until the first PSA increase that is >25% (and an absolute increase of ≥ 2 ng/ml) from the nadir PSA value following the initiation of niraparib maintenance therapy
Measure:Frequency and severity of adverse events (AEs)
Time Frame:1 month
Safety Issue:
Description:Frequency and severity of adverse events (AEs), as assessed by CTCAE version 5.0, following the initiation of niraparib maintenance therapy
Measure:Overall survival (OS)
Time Frame:12 months
Safety Issue:
Description:Time from start of study therapy to death due to any cause. Patients who are alive will be censored on the most recent date of patient contact

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Abramson Cancer Center of the University of Pennsylvania

Last Updated

February 27, 2020