A Phase 3 Randomized, Placebo-controlled, Double-blind Study of Niraparib in Combination With Abiraterone Acetate and Prednisone Versus Abiraterone Acetate and Prednisone in Subjects With Metastatic Prostate Cancer
概览
- 阶段
- 3 期
- 干预措施
- Placebo
- 疾病 / 适应症
- Castration-Resistant Prostatic Cancer
- 发起方
- Janssen Research & Development, LLC
- 入组人数
- 765
- 试验地点
- 631
- 主要终点
- Cohort 1: Radiographic Progression-Free Survival (rPFS) as Assessed by Blinded Independent Central Review (BICR)
- 状态
- 进行中（未招募）
- 最后更新
- 19天前
概览
简要总结
The purpose of this study is to evaluate the effectiveness of niraparib in combination with abiraterone acetate plus prednisone (AAP) compared to AAP and placebo.
研究者
入排标准
入选标准
- •HRR gene alteration (as identified by the sponsor's required assays) as follows:
- •Cohort 1: positive for HRR gene alteration
- •Cohort 2: not positive for DRD (that is, HRR gene alteration)
- •Cohort 3: eligible by HRR status
- •Metastatic disease documented by positive bone scan or metastatic lesions on computed tomography (CT) or magnetic resonance imaging (MRI)
- •Metastatic prostate cancer in the setting of castrate levels of testosterone less than or equal to (\<=) 50 nanogram per deciliter (ng/dL) on a gonadotropin releasing hormone analog (GnRHa) or bilateral orchiectomy
- •Able to continue GnRHa during the study if not surgically castrate
- •Score of \<= 3 on the brief pain inventory-short form (BPI-SF) question number 3 (worst pain in last 24 hours)
排除标准
- •Prior treatment with a poly (adenosine diphosphate \[ADP\]-ribose) polymerase (PARP) inhibitor
- •Systemic therapy (that is, novel second-generation AR-targeted therapy such as enzalutamide, apalutamide, or darolutamide; taxane-based chemotherapy, or more than 4 months of abiraterone acetate plus prednisone \[AAP\] prior to randomization) in the metastatic castration-resistant prostate cancer (mCRPC) setting; or AAP outside of the mCRPC setting
- •Symptomatic brain metastases
- •History or current diagnosis of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML)
- •Other prior malignancy (exceptions: adequately treated basal cell or squamous cell skin cancer, superficial bladder cancer, or any other cancer in situ currently in complete remission) \<= 2 years prior to randomization, or malignancy that currently requires active systemic therapy
研究组 & 干预措施
Cohort 1: Participants with mCRPC and HRR Gene Alteration
Participants with L1 metastatic castration-resistant prostate cancer (mCRPC) and homologous recombination repair (HRR) gene alteration will receive combination of niraparib 200 milligrams (mg) or matching placebo and abiraterone acetate (AA) 1000 mg plus prednisone 10 mg. In the open label extension (OLE) phase participants earlier receiving the combination of niraparib and AAP may continue to receive open-label combination of niraparib 200 mg and AA 1000 mg plus prednisone 10 mg and those receiving placebo and AAP may cross over depending on the outcome of study to receive open-label combination of niraparib 200 mg and AA 1000 mg plus prednisone 10 mg.
干预措施: Placebo
Cohort 2: Participants with mCRPC and No HRR Gene Alteration
Participants with L1 mCRPC and no HRR Gene alteration will receive combination of niraparib 200 mg or matching placebo and AA 1000 mg plus prednisone 10 mg. In the OLE phase participants earlier receiving the combination of niraparib and AAP may continue to receive open-label combination of niraparib 200 mg and AA 1000 mg plus prednisone 10 mg and those receiving placebo and AAP may cross over depending on the outcome of study to receive open-label combination of niraparib 200 mg and AA 1000 mg plus prednisone 10 mg.
干预措施: Placebo
Cohort 3 (Open-label): Participants with mCRPC
Participants with mCRPC will receive a new formulation of niraparib 200 mg and AA 1000 mg tablets plus prednisone 10 mg.
干预措施: New Formulation of Niraparib and Abiraterone Acetate (AA)
Cohort 1: Participants with mCRPC and HRR Gene Alteration
Participants with L1 metastatic castration-resistant prostate cancer (mCRPC) and homologous recombination repair (HRR) gene alteration will receive combination of niraparib 200 milligrams (mg) or matching placebo and abiraterone acetate (AA) 1000 mg plus prednisone 10 mg. In the open label extension (OLE) phase participants earlier receiving the combination of niraparib and AAP may continue to receive open-label combination of niraparib 200 mg and AA 1000 mg plus prednisone 10 mg and those receiving placebo and AAP may cross over depending on the outcome of study to receive open-label combination of niraparib 200 mg and AA 1000 mg plus prednisone 10 mg.
干预措施: Niraparib
Cohort 2: Participants with mCRPC and No HRR Gene Alteration
Participants with L1 mCRPC and no HRR Gene alteration will receive combination of niraparib 200 mg or matching placebo and AA 1000 mg plus prednisone 10 mg. In the OLE phase participants earlier receiving the combination of niraparib and AAP may continue to receive open-label combination of niraparib 200 mg and AA 1000 mg plus prednisone 10 mg and those receiving placebo and AAP may cross over depending on the outcome of study to receive open-label combination of niraparib 200 mg and AA 1000 mg plus prednisone 10 mg.
干预措施: Niraparib
Cohort 1: Participants with mCRPC and HRR Gene Alteration
Participants with L1 metastatic castration-resistant prostate cancer (mCRPC) and homologous recombination repair (HRR) gene alteration will receive combination of niraparib 200 milligrams (mg) or matching placebo and abiraterone acetate (AA) 1000 mg plus prednisone 10 mg. In the open label extension (OLE) phase participants earlier receiving the combination of niraparib and AAP may continue to receive open-label combination of niraparib 200 mg and AA 1000 mg plus prednisone 10 mg and those receiving placebo and AAP may cross over depending on the outcome of study to receive open-label combination of niraparib 200 mg and AA 1000 mg plus prednisone 10 mg.
干预措施: Prednisone
Cohort 2: Participants with mCRPC and No HRR Gene Alteration
Participants with L1 mCRPC and no HRR Gene alteration will receive combination of niraparib 200 mg or matching placebo and AA 1000 mg plus prednisone 10 mg. In the OLE phase participants earlier receiving the combination of niraparib and AAP may continue to receive open-label combination of niraparib 200 mg and AA 1000 mg plus prednisone 10 mg and those receiving placebo and AAP may cross over depending on the outcome of study to receive open-label combination of niraparib 200 mg and AA 1000 mg plus prednisone 10 mg.
干预措施: Abiraterone Acetate
Cohort 1: Participants with mCRPC and HRR Gene Alteration
Participants with L1 metastatic castration-resistant prostate cancer (mCRPC) and homologous recombination repair (HRR) gene alteration will receive combination of niraparib 200 milligrams (mg) or matching placebo and abiraterone acetate (AA) 1000 mg plus prednisone 10 mg. In the open label extension (OLE) phase participants earlier receiving the combination of niraparib and AAP may continue to receive open-label combination of niraparib 200 mg and AA 1000 mg plus prednisone 10 mg and those receiving placebo and AAP may cross over depending on the outcome of study to receive open-label combination of niraparib 200 mg and AA 1000 mg plus prednisone 10 mg.
干预措施: Abiraterone Acetate
Cohort 2: Participants with mCRPC and No HRR Gene Alteration
Participants with L1 mCRPC and no HRR Gene alteration will receive combination of niraparib 200 mg or matching placebo and AA 1000 mg plus prednisone 10 mg. In the OLE phase participants earlier receiving the combination of niraparib and AAP may continue to receive open-label combination of niraparib 200 mg and AA 1000 mg plus prednisone 10 mg and those receiving placebo and AAP may cross over depending on the outcome of study to receive open-label combination of niraparib 200 mg and AA 1000 mg plus prednisone 10 mg.
干预措施: Prednisone
Cohort 3 (Open-label): Participants with mCRPC
Participants with mCRPC will receive a new formulation of niraparib 200 mg and AA 1000 mg tablets plus prednisone 10 mg.
干预措施: Prednisone
结局指标
主要结局
Cohort 1: Radiographic Progression-Free Survival (rPFS) as Assessed by Blinded Independent Central Review (BICR)
时间窗: Up to 32 months
As per BICR, rPFS is time interval from the date of randomization to radiographic progression or death, whichever occurred first. Radiographic progression was determined by: (1) progression of soft tissue lesions measured by computerized tomography (CT) or magnetic resonance imaging (MRI) as per response evaluation criteria in solid tumors (RECIST) 1.1; (2) Progression of bone lesions observed by bone scan based on prostate cancer working group 3 (PCWG3) criteria. 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. Confirmatory scan \>=2 new lesions indicate progression; scan does not show \>=2 new lesions means no progression. If Week 8 scan less than (\<) 2 new bone lesions compared to baseline, the initial scan \>=2 new lesions compared to Week 8 scan indicates progression if confirmed by subsequent scan \>=6 weeks later.
Cohort 1 Breast Cancer Gene (BRCA) Subgroup: Radiographic Progression-Free Survival (rPFS) as Assessed by Blinded Independent Central Review (BICR)
时间窗: Up to 32 months
As per BICR, rPFS is time interval from the date of randomization to radiographic progression or death, whichever occurred first. Radiographic progression was determined by: (1) progression of soft tissue lesions measured by CT or MRI as per RECIST 1.1; (2) Progression of bone lesions observed by bone scan based on PCWG3 criteria. 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. Confirmatory scan \>=2 new lesions indicate progression; scan does not show \>=2 new lesions means no progression. If Week 8 scan \<2 new bone lesions compared to baseline, the initial scan \>=2 new lesions compared to Week 8 scan indicates progression if confirmed by subsequent scan \>=6 weeks later.
次要结局
- Cohort 1: Overall Survival (OS)(Up to 97 months)
- Cohort 1: Time to Symptomatic Progression(Up to 97 months)
- Cohort 1: Time to Initiation of Cytotoxic Chemotherapy(Up to 97 months)
- Observed Plasma Concentrations of Niraparib(Up to 97 months)
- Observed Plasma Concentrations of Abiraterone(Up to 97 months)
- Number of Participants With Abnormalities in Laboratory Values(Up to 96 months)
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs)(Up to 96 months)
- Number of Participants With Treatment-Emergent Adverse Events by Severity(Up to 96 months)