A Safety and Pharmacokinetics Study of Niraparib Plus Androgen Receptor-Targeted Therapy (Apalutamide or Abiraterone Acetate Plus Prednisone) in Men With Metastatic Castration-Resistant Prostate Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 34
- 主要终点
- Determine Recommended Phase 2 dose (RP2D) of Niraparib in Combination With 240 milligram (mg) Apalutamide or 1,000 mg Abiraterone Acetate Plus 10 mg Prednisone (5 mg Twice Daily) in Part 1
研究概览
简要总结
The purpose of this study is to assess the safety and pharmacokinetics of niraparib when administered in combination with an androgen receptor (AR)-targeted therapy (apalutamide or abiraterone acetate plus prednisone) in adult men with metastatic castration resistant prostate cancer (mCRPC) who may or may not have deoxyribonucleic acid (DNA)-repair anomalies.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
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
- •Histologically confirmed prostate cancer (mixed histology is acceptable, with the exception of the small cell pure phenotype, which is be excluded
- •At least 1 line of prior taxane-based chemotherapy
- •At least 1 line of prior androgen receptor (AR) targeted therapy
- •Progression of metastatic prostate cancer in the setting of castrate levels of testosterone or history of bilateral orchiectomy at study entry
- •Eastern Cooperative Oncology Group Performance Status (ECOG PS) of lesser than or equal to [<=]1
排除标准
- •Known brain metastases or history of seizure
- •Prior treatment with a poly (adenosine diphosphate [ADP] ribose) polymerase (PARP) inhibitor
- •Prior platinum-based chemotherapy for the treatment of prostate cancer
- •Known history or current diagnosis of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML)
- •Severe or unstable cardiovascular disease or uncontrolled hypertension
- •Left ventricular ejection fraction (LVEF) of lesser than [<] 50 percent (%) as determined by multiple uptake gated acquisition (MUGA) or echocardiography during screening
研究组 & 干预措施
Niraparib + Apalutamide/[Abiraterone Acetate + Prednisone]
Participants will receive initial starting dose of Niraparib 200 milligram (mg) once daily in combination either with Apalutamide 240 mg (4*60 mg) once daily or Abiraterone Acetate 1000 mg (4*250 mg) plus 10 mg Prednisone (5 mg twice daily) for 28 days of cycle 1. Once a safe dose of niraparib is selected with each Andrgen Receptor (AR)-targeted therapy [Apalutamide or Abiraterone Acetate plus Prednisone], then an expansion phase (Part 2) will open to further explore safety and assess antitumor activity.
干预措施: Niraparib (Drug)
Niraparib + Apalutamide/[Abiraterone Acetate + Prednisone]
Participants will receive initial starting dose of Niraparib 200 milligram (mg) once daily in combination either with Apalutamide 240 mg (4*60 mg) once daily or Abiraterone Acetate 1000 mg (4*250 mg) plus 10 mg Prednisone (5 mg twice daily) for 28 days of cycle 1. Once a safe dose of niraparib is selected with each Andrgen Receptor (AR)-targeted therapy [Apalutamide or Abiraterone Acetate plus Prednisone], then an expansion phase (Part 2) will open to further explore safety and assess antitumor activity.
干预措施: Apalutamide (Drug)
Niraparib + Apalutamide/[Abiraterone Acetate + Prednisone]
Participants will receive initial starting dose of Niraparib 200 milligram (mg) once daily in combination either with Apalutamide 240 mg (4*60 mg) once daily or Abiraterone Acetate 1000 mg (4*250 mg) plus 10 mg Prednisone (5 mg twice daily) for 28 days of cycle 1. Once a safe dose of niraparib is selected with each Andrgen Receptor (AR)-targeted therapy [Apalutamide or Abiraterone Acetate plus Prednisone], then an expansion phase (Part 2) will open to further explore safety and assess antitumor activity.
干预措施: Abiraterone Acetate (Drug)
Niraparib + Apalutamide/[Abiraterone Acetate + Prednisone]
Participants will receive initial starting dose of Niraparib 200 milligram (mg) once daily in combination either with Apalutamide 240 mg (4*60 mg) once daily or Abiraterone Acetate 1000 mg (4*250 mg) plus 10 mg Prednisone (5 mg twice daily) for 28 days of cycle 1. Once a safe dose of niraparib is selected with each Andrgen Receptor (AR)-targeted therapy [Apalutamide or Abiraterone Acetate plus Prednisone], then an expansion phase (Part 2) will open to further explore safety and assess antitumor activity.
干预措施: Prednisone (Drug)
结局指标
主要结局
Determine Recommended Phase 2 dose (RP2D) of Niraparib in Combination With 240 milligram (mg) Apalutamide or 1,000 mg Abiraterone Acetate Plus 10 mg Prednisone (5 mg Twice Daily) in Part 1
时间窗: Up to 56 days
RP2D will be defined as the highest dose of study drug at which less than 33 percent (%) of participants experience dose limiting toxicity (DLT).
Number of Participants With Incidence and Severity of Adverse Events (Part 2)
时间窗: Up to 30 days after last dose
Number of participants will be assessed to further explore safety and antitumor activity in Part 2 (dose expansion) of study.
次要结局
- Metabolite to Parent Ratio for Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours (AUC [0-24])(24 hours postdose on Cycle 1 Day 1 up to 10 hours postdose Cycle 3 Day 1 (each cycle 28 days))
- Maximum Observed Plasma Concentration (Cmax)(24 hours postdose on Cycle 1 Day 1 up to 10 hours postdose Cycle 3 Day 1 (each cycle 28 days))
- Trough Plasma Concentration (Ctrough)(Predose (Cycle 1 Days 15 and 22) up to Cycle 3 Day 1 (each cycle 28 days) then Every 3 Cycles after Cycle 3 till End of Treatment (30 days after last dose))
- Time to Reach the Maximum Observed Plasma Concentration (Tmax)(24 hours postdose on Cycle 1 Day 1 up to 10 hours postdose Cycle 3 Day 1 (each cycle 28 days))
- Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC [0-24])(24 hours postdose on Cycle 1 Day 1 up to 10 hours postdose Cycle 3 Day 1 (each cycle 28 days))