CYCLONE 3: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Abemaciclib in Combination With Abiraterone Plus Prednisone in Men With High-Risk Metastatic Hormone-Sensitive Prostate Cancer
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 925
- 试验地点
- 438
- 主要终点
- Radiographic Progression-Free Survival (rPFS) Assessed by Investigator
研究概览
简要总结
The purpose of this study is to learn whether adding abemaciclib to abiraterone plus prednisone prolongs the time before prostate cancer gets worse. Participation may last approximately 60 months.
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
- •Adenocarcinoma of the prostate (as the predominant histology)
- •High-risk metastatic hormone-sensitive prostate cancer. High risk is defined as:
- •Greater than or equal to (≥)4 bone metastases by bone scan and/or
- •≥1 visceral metastases by computed tomography or magnetic resonance imaging
- •Must have initiated androgen deprivation therapy (ADT) with luteinizing hormone-releasing hormone (LHRH) agonist/antagonist or bilateral orchiectomy prior to randomization. Up to 3 months of ADT prior to randomization is permitted with or without first-generation anti-androgen.
- •Adequate organ function
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
排除标准
- •Prior treatment with abemaciclib or any other cyclin dependent kinase 4 and 6 (CDK4 & 6) inhibitor
- •Development of metastatic prostate cancer in the context of castrate levels of testosterone
- •Received any prior systemic therapy for metastatic prostate cancer (including investigational agents), except for ADT and first-generation anti-androgen
- •Clinically significant cardiovascular disease as evidenced by myocardial infarction, arterial thrombotic events, or severe/unstable angina in the past 6 months, or New York Heart Association Class II to IV heart failure
- •History of syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin, or sudden cardiac arrest. Chronic and hemodynamically stable atrial arrhythmia well-controlled on medical therapy is permitted
- •Uncontrolled hypertension
- •Clinically active or chronic liver disease, moderate/severe hepatic impairment
- •Known untreated central nervous system (CNS) metastasis. Participants with a history of treated brain metastases are eligible if stable for at least 8 weeks prior to randomization and off corticosteroid for at least 2 weeks prior to randomization
研究组 & 干预措施
Abemaciclib
Participants received 200 milligram (mg) abemaciclib twice daily (BID) in combination with standard doses of 1000 mg abiraterone acetate once daily and 5mg 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)
Abemaciclib
Participants received 200 milligram (mg) abemaciclib twice daily (BID) in combination with standard doses of 1000 mg abiraterone acetate once daily and 5mg 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 (Drug)
Abemaciclib
Participants received 200 milligram (mg) abemaciclib twice daily (BID) in combination with standard doses of 1000 mg abiraterone acetate once daily and 5mg 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 or Prednisolone (Drug)
Placebo
Participants received placebo BID in combination with standard doses of 1000 mg abiraterone acetate once daily and 5mg 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 (Drug)
Placebo
Participants received placebo BID in combination with standard doses of 1000 mg abiraterone acetate once daily and 5mg 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 or Prednisolone (Drug)
Placebo
Participants received placebo BID in combination with standard doses of 1000 mg abiraterone acetate once daily and 5mg 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 for Abemaciclib (Drug)
结局指标
主要结局
Radiographic Progression-Free Survival (rPFS) Assessed by Investigator
时间窗: From Date of Randomization to Radiographic Disease Progression or Death from Any Cause (up to 22 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
- Radiographic Progression-Free Survival (rPFS) Assessed by Blinded Independent Central Review (BICR)(From Date of Randomization to Radiographic Disease Progression or Death from Any Cause (up to 22 months))
- Castration-resistant Prostate Cancer (CRPC)-Free Survival(Randomization to the earliest date of PSA or radiographic progression with a testosterone level of ≤50 ng/dL; or death from any cause (up to 22 months))
- Overall Survival (OS)(From Date of Randomization to Date of Death Due to Any Cause (Up to 22 Months))
- Time to Pain Progression(Randomization to pain progression (up to 22 months))
- Time to Deterioration in Health-Related Quality of Life (HRQoL) Measured by Functional Assessment of Cancer Therapy-Prostate (FACT-P) - Physical Well-Being Subscale(Randomization to the date of the first clinically meaningful HRQoL deterioration (up to 22 months))
- Time to Deterioration in Health-Related Quality of Life (HRQoL) Measured by Functional Assessment of Cancer Therapy-Prostate (FACT-P) - Prostate Cancer Subscale(Randomization to the date of the first clinically meaningful HRQoL deterioration (up to 22 months))
- Pharmacokinetics (PK): Maximum Plasma Concentration at Steady State (Cmax,ss) of Abemaciclib(Predose on Cycle 1 Day 1, Predose and Predose on Cycle 2 Day 1 and Predose on Cycle 3 Day 1 (28 Day Cycles))