The purpose of the study is to determine if the combination of niraparib with Abiraterone Acetate (AA) plus prednisone compared with AA plus prednisone in participants with deleterious germline or somatic Homologous Recombination Repair (HRR) gene-mutated Metastatic Castration-Sensitive Prostate Cancer (mCSPC) provides superior efficacy in improving radiographic progression-free survival (rPFS).
Prostate cancer is a heterogenous disease and recent genomic analyses have highlighted specific germline and somatic mutations and alternative driver growth signaling pathways in patients with metastatic disease. Abiraterone acetate plus prednisone (AAP) is an established standard of care for the treatment of participants with mCSPC and is included in widely accepted clinical treatment guidelines. Niraparib in combination with AAP has been approved for the treatment of BRCA-mutated Metastatic Castration-Resistant Prostate Cancer (mCRPC). Niraparib is an investigational agent in the Metastatic Castration-Sensitive Prostate Cancer (mCSPC) population. Whether the addition of niraparib to the AAP standard of care may improve initial disease control and long-term outcomes compared with AAP alone in a biomarker selected mCSPC population is being evaluated on this trial. The study will consist of 4 phases; a Prescreening Phase for biomarker evaluation for eligibility only, a Screening Phase, a Treatment Phase, and a Follow-up Phase. Efficacy evaluations include the following: tumor measurements by computed tomography (CT), magnetic resonance imaging (MRI; abdomen, chest, and pelvis), Technetium-99m (99mTc) bone scans, serum prostate sensitive antigen (PSA) evaluations, and patient reported outcomes (PROs). Safety evaluations include incidence of adverse events and clinical laboratory parameters.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
696
Participants will receive Niraparib 200 mg once daily.
Participants will receive AA 1000 mg once daily.
Participants will receive prednisone 5 mg once daily.
Participants will receive matching placebo for Niraparib once daily.
Urology Centers Of Alabama
Homewood, Alabama, United States
Mayo Clinic Arizona
Phoenix, Arizona, United States
Urological Associates of Southern Arizona, P.C.
Tucson, Arizona, United States
Greater Los Angeles VA Healthcare System
Los Angeles, California, United States
University of California Irvine Medical Center Chao Family Comprehensive Cancer Center
Orange, California, United States
Breast Cancer Gene (BRCA) Subgroup: Radiographic Progression-free Survival (rPFS) Assessed by Investigator
rPFS: time interval from date of randomization to first date of radiographic progression as assessed by investigator or death due to any cause, whichever occurred first. rPFS was determined by: (1) progression of soft tissue lesions measured by computerized tomography (CT) or magnetic resonance imaging (MRI) per response evaluation criteria in solid tumors (RECIST) 1.1; (2) progression of bone lesions observed by bone scan per prostate cancer working group 3 (PCWG3) criteria: bone progression was confirmed by subsequent scan greater than or equal to (\>=) 6 weeks later. Week 8 scan was baseline to which all subsequent scans were compared to determine progression. A confirmatory scan with \>=2 new lesions indicated progression; A confirmatory scan not showing \>=2 new lesions means no progression. If Week 8 scan shows \<2 new bone lesions compared to baseline, first scan with \>=2 new lesions compared to Week 8 scan indicated progression, when confirmed by a subsequent scan \>=6 weeks later.
Time frame: From date of randomization (Day -3 to Day 1) up to approximately 49 months
HRR Effector Subgroup: Radiographic Progression-free Survival (rPFS) Assessed by Investigator
rPFS: time interval from date of randomization to first date of radiographic progression as assessed by investigator or death due to any cause, whichever occurred first. rPFS was determined by: (1) progression of soft tissue lesions measured by CT or MRI per RECIST 1.1; (2) progression of bone lesions observed by bone scan per PCWG3 criteria: bone progression was confirmed by subsequent scan \>= 6 weeks later. Week 8 scan was baseline to which all subsequent scans were compared to determine progression. A confirmatory scan with \>=2 new lesions indicated progression; A confirmatory scan not showing \>=2 new lesions means no progression. If Week 8 scan shows \<2 new bone lesions compared to baseline, first scan with \>=2 new lesions compared to Week 8 scan indicated progression, when confirmed by a subsequent scan \>=6 weeks later.
Time frame: From date of randomization (Day -3 to Day 1) up to approximately 49 months
All HRR: Radiographic Progression-free Survival (rPFS) Assessed by Investigator
rPFS: time interval from date of randomization to first date of radiographic progression as assessed by investigator or death due to any cause, whichever occurred first. rPFS was determined by: (1) progression of soft tissue lesions measured by CT or MRI per RECIST 1.1; (2) progression of bone lesions observed by bone scan per PCWG3 criteria: bone progression was confirmed by subsequent scan \>= 6 weeks later. Week 8 scan was baseline to which all subsequent scans were compared to determine progression. A confirmatory scan with \>=2 new lesions indicated progression; A confirmatory scan not showing \>=2 new lesions means no progression. If Week 8 scan shows \<2 new bone lesions compared to baseline, first scan with \>=2 new lesions compared to Week 8 scan indicated progression, when confirmed by a subsequent scan \>=6 weeks later.
Time frame: From date of randomization (Day -3 to Day 1) up to approximately 49 months
BRCA Subgroup: Time to Symptomatic Progression
Time to symptomatic progression was defined as time from the date of randomization to the date of any of the following (whichever occurred first): (a) the use of external beam radiation therapy for skeletal or pelvic symptoms, (b) the need for tumor-related orthopedic surgical intervention, (c) other cancer-related procedures (example: nephrostomy insertion, bladder catheter insertion, external beam radiation therapy, or surgery for tumor symptoms), (d) cancer-related morbid events (that is, fracture \[symptomatic and/or pathologic\], cord compression, urinary obstructive events), (e) initiation of a new systemic anti-cancer therapy because of cancer symptoms.
Time frame: From date of randomization (Day -3 to Day 1) up to approximately 49 months
HRR Effector Subgroup: Time to Symptomatic Progression
Time to symptomatic progression was defined as time from the date of randomization to the date of any of the following (whichever occurred first): (a) the use of external beam radiation therapy for skeletal or pelvic symptoms, (b) the need for tumor-related orthopedic surgical intervention, (c) other cancer-related procedures (example: nephrostomy insertion, bladder catheter insertion, external beam radiation therapy, or surgery for tumor symptoms), (d) cancer-related morbid events (that is, fracture \[symptomatic and/or pathologic\], cord compression, urinary obstructive events), (e) initiation of a new systemic anti-cancer therapy because of cancer symptoms.
Time frame: From date of randomization (Day -3 to Day 1) up to approximately 49 months
All HRR: Time to Symptomatic Progression
Time to symptomatic progression was defined as time from the date of randomization to the date of any of the following (whichever occurred first): (a) the use of external beam radiation therapy for skeletal or pelvic symptoms, (b) the need for tumor-related orthopedic surgical intervention, (c) other cancer-related procedures (example: nephrostomy insertion, bladder catheter insertion, external beam radiation therapy, or surgery for tumor symptoms), (d) cancer-related morbid events (that is, fracture \[symptomatic and/or pathologic\], cord compression, urinary obstructive events), (e) initiation of a new systemic anti-cancer therapy because of cancer symptoms.
Time frame: From date of randomization (Day -3 to Day 1) up to approximately 49 months
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San Bernardino Urological Associates
San Bernardino, California, United States
University of San Francisco California
San Francisco, California, United States
Rocky Mountain Cancer Centers
Colorado Springs, Colorado, United States
AdventHealth Medical Group Urology of Denver
Denver, Colorado, United States
Colorado Clinical Research
Lakewood, Colorado, United States
...and 377 more locations
Overall Survival (OS)
Time frame: From date of randomization (Day -3 to Day 1) up to 83 months
Time to Subsequent Therapy
Time frame: From date of randomization (Day -3 to Day 1) up to 83 months
Number of Participants With Treatment-emergent Serious Adverse Events
Time frame: From Cycle 1 Day 1 up to 83 months
Number of Participants With Treatment-emergent Adverse Events by Severity
Time frame: From Cycle 1 Day 1 up to 83 months