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).

A Study of Niraparib in Combination With Abiraterone Acetate and Prednisone Versus Abiraterone Acetate and Prednisone for the Treatment of Participants With Deleterious Germline or Somatic Homologous Recombination Repair (HRR) Gene-Mutated Metastatic Castration-Sensitive Prostate Cancer (mCSPC)

Metastatic Castration-sensitive Prostate Cancer

Metastatic Castrate-sensitive Prostate Cancer

Metastatic Prostate Cancer

Genitourinary Cancer

Advanced Solid Tumors

Prostate Neoplasms

Cancer

Advanced Solid Malignancies

Advanced Solid Tumor

Solid Tumor, Adult

Neoplasms

Adenocarcinoma

Advanced Stage Solid Tumors

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.

Prednisone

Niraparib

Abiraterone acetate (AA)

Placebo for Niraparib

A Phase 3 Randomized, Placebo-controlled, Double-blind Study of Niraparib in Combination With Abiraterone Acetate and Prednisone Versus Abiraterone Acetate and Prednisone for the Treatment of Participants With Deleterious Germline or Somatic Homologous Recombination Repair (HRR) Gene-Mutated Metastatic Castration-Sensitive Prostate Cancer (mCSPC)

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.

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 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.

Participants will receive the following in each 28-day treatment cycle: niraparib 200 milligrams (mg), abiraterone acetate (AA) 1000 mg plus prednisone 5 mg once daily.

Participants will receive the following in each 28-day treatment cycle: matching placebo for Niraparib along with AA 1000 mg plus prednisone 5 mg once daily.

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 is an investigational agent in the
      castration-sensitive cancer population and has been approved for the treatment of ovarian
      cancer. The addition of niraparib to the AAP backbone regimen may improve initial disease
      control and long-term outcomes compared with AAP alone in a biomarker selected population.
      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.

Urology Centers Of Alabama

Mayo Clinic Arizona

Urological Associates of Southern Arizona, P.C.

Greater Los Angeles VA Healthcare System

University of California Irvine Medical Center - Chao Family Comprehensive Cancer Center

San Bernardino Urological Associates

University of San Francisco California

Rocky Mountain Cancer Centers

The Urology Center of Colorado

Colorado Clinical Research

Eastern Connecticut Hematology & Oncology Assoc.

Advanced Urology Institute

Holy Cross Hospital - Michael and Dianne Bienes Comprehensive Cancer Center

University of Florida Health Jacksonville

Cancer Specialists of North Florida

Urology of Indiana

First Urology

Ochsner Clinic Foundation

Baltimore VA Medical Center

Maryland Oncology Hematology, PA

Chesapeake Urology Associates

Michigan Institute of Urology

Mosaic Life Care

St. Louis VA Medical Center

GU Research Network

New York Oncology Hematology

Montefiore Medical Center

Manhattan VAMC

Mount Sinai

Memorial Sloan Kettering Cancer Center

Associated Medical Professionals

Durham VAMC

Stephenson Cancer Center

VA Portland Health Care System

Oregon Oncology Specialists

Keystone Urology Specialists

Philadelphia VA Medical Center

University of Pennsylvania

University of Pittsburgh Medical Center (UPMC)

Ralph H. Johnson Veterans Affairs Medical Center

Prisma Health

Urology Associates

Texas Oncology-Austin

Texas Oncology-Denton South

Houston Metro Urology

Texas Oncology P.A.

Texas Oncology-Tyler

University of Utah Huntsman Cancer Institute

Virginia Oncology Associates

Virginia Commonwealth University - Massey Cancer Center

VA Puget Sound Healthcare System

Seattle Cancer Care Alliance

MultiCare Health System

Sociedade Beneficente de Senhoras - Hospital Sírio Libanês

Centro Oncológico Korben

Hospital Militar Cosme Argerich

CINME - Centro de Investigaciones Metabolicas

CIPREC Arenales

Centro de Urologia (CDU)

Hospital Italiano de Buenos Aires

Clínica Adventista Belgrano

Cemaic - Centro Privado de Especialidades Medicas Ambulatorias e Investigacion Clinica

Centro Urologico Profesor Bengio

Instituto Médico de Río Cuarto

Hospital Privado de Cordoba

Hospital Privado de Comunidad

Centro de Investigacion Pergamino SA

ARS Médica

Sunshine Coast University Hospital

St. Vincent's Hospital Sydney

Royal Brisbane and Women's Hospital

Royal Hobart Hospital

Ashford Cancer Centre

Liverpool Hospital

Peter MacCallum Cancer Centre

Fiona Stanley Hospital

Macquarie University Hospital

ICON Cancer Care

St John of God Subiaco Hospital

Bobruisk Interregional Oncological Dispensary

Brest Regional Oncology Dispensary

Gomel Regional Clinical Oncology Dispensary

Grodno University Hospital

State Institution N.N. Alexandrov Republican Scientific and

Minsk city Clinical Oncological Dispensary

Mogilev Regional Hospital

Vitebsk Regional Clinical Hospital

ZNA Middelheim

Grand Hopital de Charleroi, site Notre Dame

Jolimont

CHC MontLegia

CHU UCL Namur - Site Sainte Elisabeth

Clinique St Pierre

Algemeen Ziekenhuis Delta

GZA Ziekenhuizen

Fundacao Pio XII

Cetus Oncologia

PERSONAL - Oncologia de Precisão e Personalizada

CIONC - Centro Integrado de Oncologia de Curitiba

Centro de Pesquisa e Ensino em Oncologia de Santa Catarina - CEPEN

rPFS is defined as time from randomization date to date of radiographic progression or death, whichever occurs first. Radiographic progression will be evaluated by Prostate Cancer Working Group 3 (PCWG3) criteria and Response Evaluation Criteria in Solid Tumors (RECIST 1.1).

OS is defined as the time from date of randomization to date of death from any cause.

Time to symptomatic progression is defined as time from the date of randomization to the date of any of the following (whichever occurs 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; d) cancer-related morbid events; e) initiation of a new systemic anti-cancer therapy because of cancer symptoms.

Time to Subsequent Therapy is defined as the time from date of randomization to the date of initiation of subsequent therapy for prostate cancer.

An adverse event (AE) is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non investigational) product. AE does not necessarily have a causal relationship with intervention.

AdventHealth Medical Group Urology of Denver

Prostate Cancer Centre

Centre Oscar Lambret

Universitaetsklinikum Koelnt

Medisport

Royal Marsden Hospital

Texas Oncology P A

Texas Oncology - Northeast 1

Fred Hutchinson Cancer Research Center

Icon Cancer Centre Kurralta Park

Vitebsk Regional Clinical Oncology Dispensary

PERSONAL Oncologia de Precisao e Personalizada

CIONC Centro Integrado de Oncologia de Curitiba

Fundacao Sao Francisco Xavier

UPCO Unidade de Pesquisa Clinica em Oncologia

Irmandade Santa Casa de Misericordia de Porto Alegre

Oncoclinicas Rio de Janeiro S A

Instituto de Educacao, Pesquisa e Gestao em Saude Instituto Americas (COI)

Nucleo de Oncologia da Bahia

Instituto de Ensino e Pesquisa São Lucas

Fundacao Faculdade de Medicina - Instituto do Cancer do Estado de Sao Paulo

Real e Benemerita Associacao Portuguesa de Beneficencia

Hospital Alemao Oswaldo Cruz

Núcleo de Pesquisa São Camilo

UMHAT Dr Georgi Stranski EAD 1

Complex Oncology Center - Plovdiv EOOD

Multifunctional Hospital for Active Treatment for Women Health Nadezhda

Specialized Hospital for Active Treatment in Oncology

UMHAT Sofia Med

Comprehensive Cancer Center

Cross Cancer Institute

British Columbia Cancer Agency(BCCA)-Sindi Ahluwalia Hawkins Centre for the Southern Interior(CSI)

A Study of Niraparib in Combination With Abiraterone Acetate and Prednisone Versus Abiraterone Acetate and Prednisone for the Treatment of Participants With Deleterious Germline or Somatic Homologous Recombination Repair (HRR) Gene-Mutated Metastatic Castration-Sensitive Prostate Cancer (mCSPC)

Trials at a glance

Trials at a glance

A Study of Niraparib in Combination With Abiraterone Acetate and Prednisone Versus Abiraterone Acetate and Prednisone for the Treatment of Participants With Deleterious Germline or Somatic Homologous Recombination Repair (HRR) Gene-Mutated Metastatic Castration-Sensitive Prostate Cancer (mCSPC)

Outcome measures

Primary outcome measures

Secondary outcome measures