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.
Title
- Brief Title: A 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
Interventions
Drug | Synonyms | Arms |
---|
Niraparib Pill | | Niraparib 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
Name | Type | Description | Interventions |
---|
Niraparib Arm (only arm) | Other | Niraparib 200 mg by mouth daily (2 x 100 mg pills) on a 28 day cycle | |
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: | Recruiting |
Lead Sponsor: | Abramson Cancer Center of the University of Pennsylvania |
Last Updated
February 26, 2021