Niraparib Maintenance for the Treatment of Metastatic Castration-Resistant Prostate Cancer
- 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 Common Terminology Criteria for Adverse Events [CTCAE] version 5)
- Eastern Cooperative Oncology Group (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 Clinical Laboratory Improvement Act (CLIA) certified laboratory
- Radiographic evidence for metastatic disease. Measurable disease (per Response Evaluation Criteria in Solid Tumors [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
- Absolute neutrophil count (ANC) >= 1.5 x 10^9/L (obtained =< 14 calendar days prior to the first day of study therapy)
- Platelet count >= 100 x 10^9/L (obtained =< 14 calendar days prior to the first day of study therapy)
- Hemoglobin >= 9 g/dL (may have been transfused) (obtained =< 14 calendar days prior to the first day of study therapy)
- Total bilirubin level =< 1.5 x the upper limit of normal (ULN) range (Note: In subjects with Gilbert’s syndrome, if total bilirubin is > 1.5 x ULN, measure direct and indirect bilirubin and if direct bilirubin is =< 1.5 x ULN, subject may be eligible) (obtained =< 14 calendar days prior to the first day of study therapy)
- 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 calendar days prior to the first day of study therapy)
- Estimated creatinine clearance >= 45 mL/min using Cockcroft Gault formula (obtained =< 14 calendar days prior to the first day of study therapy)
- Patients must have a projected life expectancy of at least 3 months
- 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
I. To evaluate the efficacy of maintenance niraparib tosylate monohydrate (niraparib) by assessment of the 6-month radiographic progression-free survival (rPFS) rate in patients with platinum-sensitive metastatic castration-resistant prostate carcinoma (mCRPC) harboring germline or somatic DNA repair defects.
I. To assess the effects of maintenance niraparib on prostate specific antigen (PSA) response rates (PSA30: >= 30% decline and PSA50: >= 50% decline) in patients with platinum-sensitive mCRPC harboring germline or somatic DNA repair defects.
II. To assess the effects of maintenance niraparib on the time to PSA progression (as defined by first PSA increase that is > 25% and an absolute increase of >= 2 ng/ml from nadir) in patients with platinum-sensitive mCRPC harboring germline or somatic DNA repair defects.
III. To evaluate the safety of maintenance niraparib in patients with platinum-sensitive mCRPC harboring germline or somatic DNA repair defects.
IV. To estimate overall survival (OS) following maintenance niraparib therapy in patients with platinum-sensitive mCRPC harboring germline or somatic DNA repair defects.
Patients receive niraparib orally (PO) daily on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 and 90 days, and then every 12 weeks thereafter.
Trial Phase Phase II
Trial Type Treatment
University of Pennsylvania / Abramson Cancer Center
Vivek K. Narayan
- Primary ID UPCC 21819
- Secondary IDs NCI-2021-00570
- Clinicaltrials.gov ID NCT04288687