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临床试验/NCT04497844
NCT04497844进行中(未招募)3 期

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)

Janssen Research & Development, LLC388 个研究点 分布在 2 个国家目标入组 696 人开始时间: 2020年9月23日最近更新:
适应症
干预措施
相关药物

试验速览

阶段
3 期
状态
进行中(未招募)
入组人数
696
试验地点
388
主要终点
Breast Cancer Gene (BRCA) Subgroup: Radiographic Progression-free Survival (rPFS) Assessed by Investigator

研究概览

简要总结

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).

详细描述

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.

研究设计

研究类型
Interventional
分配方式
Randomized
干预模型
Parallel
主要目的
Treatment
盲法
Triple (Participant, Investigator, Outcomes Assessor)

入排标准

年龄范围
18 Years 至 —(Adult, Older Adult)
性别
Male
接受健康志愿者
否

入选标准

  • •Pathological diagnosis of prostate adenocarcinoma
  • •Must have appropriate deleterious homologous recombination repair (HRR) gene alteration
  • •Metastatic disease as documented by conventional imaging with computed tomography (CT) or magnetic resonance imaging (MRI) (for soft tissue lesions) or 99mTc bone scan (for bone lesions). Participants with a single bone lesion on Technetium-99m (99mTc) bone scan with no other non-nodal metastatic disease must have confirmation of bone metastasis by CT or MRI. Participants with lymph node-only disease are not eligible
  • •Androgen deprivation therapy (either medical or surgical castration) must have been started >=14 days prior to randomization and participants be willing to continue androgen deprivation therapy (ADT) through the treatment phase
  • •Other allowed prior therapy for metastatic castration-sensitive prostate cancer (mCSPC): (a) maximum of 1 course of radiation and 1 surgical intervention for symptomatic control of prostate cancer (example, uncontrolled pain, impending spinal cord compression or obstructive symptoms). Participants with radiation or surgical interventions to all known sites of metastatic disease will be excluded from trial participation. Radiation must be completed prior to randomization (b) Up to a maximum of 6 months of ADT prior to randomization; (c) Up to a maximum of 45 days of abiraterone acetate + prednisone (AA-P) prior to randomization (d) Up to a maximum of 2 weeks of ketoconazole for prostate cancer prior to randomization

排除标准

  • •Prior treatment with a poly (adenosine diphosphate-ribose) polymerase inhibitor (PARP inhibitor)
  • •History of adrenal dysfunction
  • •Long-term use of systemically administered corticosteroids (greater than [>] 5 milligrams [mg] of prednisone or the equivalent) during the study is not allowed. Short-term use (<=4 weeks, including taper) and locally administered steroids (for example, inhaled, topical, ophthalmic, and intra-articular) are allowed, if clinically indicated
  • •History or current diagnosis of myelodysplastic syndrome (MDS)/ acute myeloid leukemia (AML)

研究组 & 干预措施

Placebo for Niraparib + AA FDC plus AA and prednisone (AAP)

Active Comparator

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

干预措施: Placebo FDC (Drug)

Placebo for Niraparib + AA FDC plus AA and prednisone (AAP)

Active Comparator

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

干预措施: Abiraterone acetate (AA) (Drug)

Placebo for Niraparib + AA FDC plus AA and prednisone (AAP)

Active Comparator

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

干预措施: Prednisone (Drug)

Niraparib with Abiraterone Acetate plus Prednisone (AAP)

Experimental

Participants will receive the following in each 28-day treatment cycle: niraparib 200 milligrams (mg) + abiraterone acetate (AA) 1000 mg fixed dose combination (FDC) along with placebo for AA and prednisone 5 mg once daily.

干预措施: Prednisone (Drug)

Niraparib with Abiraterone Acetate plus Prednisone (AAP)

Experimental

Participants will receive the following in each 28-day treatment cycle: niraparib 200 milligrams (mg) + abiraterone acetate (AA) 1000 mg fixed dose combination (FDC) along with placebo for AA and prednisone 5 mg once daily.

干预措施: Niraparib+ Abiraterone acetate fixed dose combination (FDC) (Combination Product)

Niraparib with Abiraterone Acetate plus Prednisone (AAP)

Experimental

Participants will receive the following in each 28-day treatment cycle: niraparib 200 milligrams (mg) + abiraterone acetate (AA) 1000 mg fixed dose combination (FDC) along with placebo for AA and prednisone 5 mg once daily.

干预措施: Placebo AA (Drug)

结局指标

主要结局

Breast Cancer Gene (BRCA) Subgroup: Radiographic Progression-free Survival (rPFS) Assessed by Investigator

时间窗: From date of randomization (Day -3 to Day 1) up to approximately 49 months

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.

HRR Effector Subgroup: Radiographic Progression-free Survival (rPFS) Assessed by Investigator

时间窗: From date of randomization (Day -3 to Day 1) up to approximately 49 months

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.

All HRR: Radiographic Progression-free Survival (rPFS) Assessed by Investigator

时间窗: From date of randomization (Day -3 to Day 1) up to approximately 49 months

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.

次要结局

  • BRCA Subgroup: Time to Symptomatic Progression(From date of randomization (Day -3 to Day 1) up to approximately 49 months)
  • HRR Effector Subgroup: Time to Symptomatic Progression(From date of randomization (Day -3 to Day 1) up to approximately 49 months)
  • All HRR: Time to Symptomatic Progression(From date of randomization (Day -3 to Day 1) up to approximately 49 months)
  • Overall Survival (OS)(From date of randomization (Day -3 to Day 1) up to 83 months)
  • Time to Subsequent Therapy(From date of randomization (Day -3 to Day 1) up to 83 months)
  • Number of Participants With Treatment-emergent Serious Adverse Events(From Cycle 1 Day 1 up to 83 months)
  • Number of Participants With Treatment-emergent Adverse Events by Severity(From Cycle 1 Day 1 up to 83 months)

研究者

申办方类型
Industry
责任方
Sponsor

研究点 (388)

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