A Phase 2/3, Randomized, Double-Blind, Placebo-Controlled Study of Abiraterone Acetate Plus Prednisone With or Without Abemaciclib in Patients With Metastatic Castration-Resistant Prostate Cancer
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 393
- 试验地点
- 112
- 主要终点
- Radiographic Progression Free Survival (rPFS)
研究概览
简要总结
This study is being done to see how safe and effective abemaciclib is when given together with abiraterone acetate plus prednisone in participants with metastatic castration resistant prostate cancer. Prednisolone may be used instead of prednisone per local regulation.
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
- Double (Participant, Investigator)
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 adenocarcinoma of the prostate.
- •Metastatic prostate cancer documented by positive bone scan and/or measurable soft tissue metastatic lesions by CT or magnetic resonance imaging (MRI).
- •Progressive disease at study entry demonstrated during continuous androgen-deprivation therapy (ADT)/post orchiectomy defined as one or more of the following:
- •PSA progression
- •Radiographic progression per Response Evaluation Criteria in Solid Tumors (RECIST)1.1 for soft tissue and/or per Prostate Cancer Working Group 3 (PCWG3) for bone, with or without PSA progression
- •Have adequate organ function.
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1.
排除标准
- •Prior therapy with cytochrome P450 (CYP)17 inhibitors.
- •Prior treatment with abemaciclib or any cyclin-dependent kinase (CDK) 4 & 6 inhibitors.
- •Prior cytotoxic chemotherapy for metastatic castration resistant prostate cancer (participants treated with docetaxel in the metastatic hormone-sensitive prostate cancer [mHSPC] are eligible). Prior radiopharmaceuticals for prostate cancer, or prior enzalutamide, apalutamide, darolutamide or sipuleucel-T. Participants who had prior radiation or surgery to all target lesions.
- •Currently enrolled in a clinical study involving an investigational product.
- •Gastrointestinal disorder affecting the absorption or ability to swallow large pills.
- •Clinically significant heart disease, active or chronic liver disease, moderate/severe hepatic impairment (Child-Pugh Class B and C).
研究组 & 干预措施
Abemaciclib
Participants received 200 milligrams (mg) abemaciclib twice daily (BID) in combination with standard doses of 1000 mg abiraterone acetate once daily and 5 mg prednisone BID administered orally on a continuous dosing schedule on days 1 through 28 of a 28-day cycle until radiographic and/or symptomatic progression or until another discontinuation criterion is met.
干预措施: Abiraterone acetate (Drug)
Placebo
Participants received placebo BID in combination with standard doses of 1000 mg abiraterone acetate once daily and 5 mg prednisone BID administered orally on a continuous dosing schedule on days 1 through 28 of a 28-day cycle until radiographic and/or symptomatic progression or until another discontinuation criterion is met.
干预措施: Abiraterone acetate (Drug)
Abemaciclib
Participants received 200 milligrams (mg) abemaciclib twice daily (BID) in combination with standard doses of 1000 mg abiraterone acetate once daily and 5 mg prednisone BID administered orally on a continuous dosing schedule on days 1 through 28 of a 28-day cycle until radiographic and/or symptomatic progression or until another discontinuation criterion is met.
干预措施: Prednisone (Drug)
Placebo
Participants received placebo BID in combination with standard doses of 1000 mg abiraterone acetate once daily and 5 mg prednisone BID administered orally on a continuous dosing schedule on days 1 through 28 of a 28-day cycle until radiographic and/or symptomatic progression or until another discontinuation criterion is met.
干预措施: Prednisone (Drug)
Abemaciclib
Participants received 200 milligrams (mg) abemaciclib twice daily (BID) in combination with standard doses of 1000 mg abiraterone acetate once daily and 5 mg prednisone BID administered orally on a continuous dosing schedule on days 1 through 28 of a 28-day cycle until radiographic and/or symptomatic progression or until another discontinuation criterion is met.
干预措施: Abemaciclib (Drug)
Placebo
Participants received placebo BID in combination with standard doses of 1000 mg abiraterone acetate once daily and 5 mg prednisone BID administered orally on a continuous dosing schedule on days 1 through 28 of a 28-day cycle until radiographic and/or symptomatic progression or until another discontinuation criterion is met.
干预措施: Placebo (Drug)
结局指标
主要结局
Radiographic Progression Free Survival (rPFS)
时间窗: From Date of Randomization to Radiographic Disease Progression or Death from Any Cause (Up to 60 Months)
The rPFS time is measured from the date of randomization to the earliest date of investigator determined radiographic disease progression (by objective radiographic disease assessment per response evaluation criteria in solid tumors (RECIST) version 1.1 for soft tissue AND/OR radionuclide bone scan using prostate cancer working group 3 -PCWG3 criteria for bone) or death from any cause, whichever occurs first.
次要结局
- Time to Prostate-Specific Antigen (PSA) Progression(From Date of Randomization to the Date of the First Observation of PSA Progression (Up to 60 Months))
- Radiographic Progression Free Survival (rPFS) Determined by Blinded Independent Central Review(From Date of Randomization Until Radiographic Disease Progression or Death from Any Cause (Up to 60 Months))
- Objective Response Rate (ORR): Percentage of Participants With a Complete Response (CR) or Partial Response (PR)(Baseline to Radiographic Disease Progression (Up to 60 Months))
- Duration of Response (DOR)(Date of First Documented CR or PR to Date of Radiographic Disease Progression or Death from Any Cause (Up to 60 Months))
- Overall Survival (OS)(From Date of Randomization to Date of Death Due to Any Cause (Up to 60 Months))
- Time to Symptomatic Progression(From Randomization to the Date of the First Documented Symptomatic Progression (Up to 60 Months))
- Pharmacokinetics (PK): Mean Steady State Exposure of Abemaciclib(Cycle (C) 1 Day (D) 1: Predose, 30 min post-dose; C1 D15, C2 D1, C2 D15, C3 D1: Post dose (28 Days Cycle))
- PK: Mean Steady State Exposure of Abemaciclib Metabolite LSN2839567(C1 D1: Predose, 30 min post-dose; C1 D15, C2 D1, C2 D15, C3 D1: Post dose (28 Days Cycle))
- PK: Mean Steady State Exposure of Abemaciclib Metabolite LSN3106726(C1 D1: Predose, 30 min post-dose; C1 D15, C2 D1, C2 D15, C3 D1: Post dose (28 Days Cycle))
- Time to Worst Pain Progression(From Randomization Through Follow-up (Up to 60 months))
- PK: Mean Steady State Exposure of Abiraterone Acetate(C1 D15, Post dose)