A Phase 3 Study to Evaluate the Efficacy and Safety of Docetaxel and Prednisone With or Without Lenalidomide in Subjects With Castrate-Resistant Prostate Cancer (CRPC)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Celgene
- 入组人数
- 1,059
- 试验地点
- 209
- 主要终点
- Overall Survival (OS)
研究概览
简要总结
The purpose of the study is to determine whether lenalidomide is safe and effective for use in combination with docetaxel and prednisone for the treatment of subjects with metastatic Castrate-Resistant Prostate Cancer.
The addition of lenalidomide to docetaxel and prednisone is proposed to increase the life expectancy of these subjects.
详细描述
In November 2011, the Data Monitoring Committee concluded it was unlikely that the study would meet its primary endpoint of overall survival (OS) and recommended that the study be stopped. The study was terminated in accordance with this recommendation. All sites were instructed to immediately discontinue all patients from experimental lenalidomide/placebo treatment administered either in combination with chemotherapy or as a single agent following chemotherapy discontinuation. Subsequently, Protocol Amendment 3 was issued to provide for the following:
To continue to collect information on Second Primary Malignancies (SPMs) and additional treatments for Prostate Cancer in all randomized subjects during survival follow-up.
To continue to provide docetaxel and prednisone for up to 10 cycles to subjects randomized at non-US sites who were ongoing in the CC-5013-PC-002 protocol when the decision was made to discontinue lenalidomide/placebo and who were experiencing benefit as per investigator discretion. For subjects who had exceeded 10 cycles of docetaxel and prednisone at the time of Protocol Amendment 3 approval, an additional two cycles were provided.
All references to dosing and study procedures pertaining to the safety, efficacy, and exploratory endpoints of lenalidomide/placebo were discontinued as part of Protocol Amendment 3.
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
- Quadruple (Participant, Care Provider, 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
- •Must sign an Informed Consent Form (ICF)
- •Males ≥ 18 years of age
- •Able to adhere to the study visit schedule and requirements of the protocol
- •Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
- •Life expectancy of ≥ 12 weeks
- •Willingness to participate in Patient-Reported Outcomes assessments
- •Serum testosterone levels < 50 ng/dL
- •Confirmed metastatic adenocarcinoma of the prostate that is unresponsive or refractory to hormonal therapy
- •Have documented disease progression while receiving or following hormonal therapy as determined by increasing Serum Prostate Specific Antigen (PSA) level, Radiological Progression, or ≥2 new bone lesions
- •Subjects must agree to receive counseling related to pregnancy precautions, teratogenic and other risks of lenalidomide
- •Refrain from donating blood or semen as defined by protocol
排除标准
- •A history of clinically significant disease that places subject at an unacceptable risk for study entry
- •Prior Therapy with thalidomide, lenalidomide or pomalidomide
- •Prior chemotherapy for prostate cancer
- •Use of any other experimental drug or therapy within 28 days prior to randomization
- •Prior radiation to ≥ 30% of bone marrow or any radiation therapy within 28 days prior to randomization
- •Prior use of Strontium-89 at any time or Samarium-153 within 56 days prior to randomization
- •Surgery within 28 days prior to randomization
- •Concurrent anti-androgen therapy
- •Abnormal serum chemistry or hematology laboratory values
- •Significant active cardiac disease within the previous 6 months:
- •Thrombotic or thromboembolic events within the past 6 months:
- •History of peripheral neuropathy of ≥grade 2
- •History of severe hypersensitivity reaction to drugs formulated with polysorbate 80
- •History of Central nervous system (CNS) or brain metastases
- •History of malignancies other than prostate cancer within the past 5 years, with the exception of treated basal cell/squamous cell carcinoma of the skin
- •Concurrent use of alternative cancer therapies
研究组 & 干预措施
Docetaxel, Prednisone, Lenalidomide (DPL)
25 mg lenalidomide orally once each day on Days 1-14; 75 mg/m2 docetaxel intravenously on Day 1; 5 mg prednisone orally twice daily on each day of the treatment cycle
干预措施: Lenalidomide (Drug)
Docetaxel, Prednisone, Lenalidomide (DPL)
25 mg lenalidomide orally once each day on Days 1-14; 75 mg/m2 docetaxel intravenously on Day 1; 5 mg prednisone orally twice daily on each day of the treatment cycle
干预措施: Docetaxel (Drug)
Docetaxel, Prednisone, Lenalidomide (DPL)
25 mg lenalidomide orally once each day on Days 1-14; 75 mg/m2 docetaxel intravenously on Day 1; 5 mg prednisone orally twice daily on each day of the treatment cycle
干预措施: Prednisone (Drug)
Docetaxel and Prednisone (DP)
Oral placebo once each day on Days 1-14 of the treatment cycle; 75 mg/m2 docetaxel intravenously on Day 1; 5 mg prednisone orally twice each day on each day of the treatment cycle
干预措施: Docetaxel (Drug)
Docetaxel and Prednisone (DP)
Oral placebo once each day on Days 1-14 of the treatment cycle; 75 mg/m2 docetaxel intravenously on Day 1; 5 mg prednisone orally twice each day on each day of the treatment cycle
干预措施: Prednisone (Drug)
Docetaxel and Prednisone (DP)
Oral placebo once each day on Days 1-14 of the treatment cycle; 75 mg/m2 docetaxel intravenously on Day 1; 5 mg prednisone orally twice each day on each day of the treatment cycle
干预措施: Placebo (Drug)
结局指标
主要结局
Overall Survival (OS)
时间窗: From randomization until death from any cause up to the cut-off date of 13 January 2012; up to approximately 26 months
Overall survival (OS) was the time from the date of randomization to the date of death from any cause. If no death was reported for a participant before the cut-off date for OS analysis, OS was censored at the last date at which the participant was alive. The median OS was calculated based on Kaplan-Meier estimates and corresponding 95% confidence interval (CI) was calculated using the method provided by Brookmeyer and Crowley.
次要结局
- Progression-Free Survival (PFS)(From randomization until disease progression or death from any cause; up to the cut-off date of 13 Jan 2012; maximum time on study was approximately 26 months)
- Percentage of Participants With an Objective Response According to Response Evaluation Criteria in Solid Tumors - RECIST Version 1.1 Criteria(From day 1 to data cut-off 13 January 2012; maximum time on study was approximately 26 months)
- Number of Participants With Treatment Emergent Adverse Events (AEs)(From the time from of first dose of study drug administration to 28 days after the last dose of study drug and up to the data cut off date of 13 January 2012; the maximum duration of study drug was 93 weeks for DP and 90.6 weeks for DPL)
- Percentage of Participants Who Received Post-Study Therapies(The date when the first consent form was signed to the last date of AE data collection;up to 5 years; up to the date of the final data analysis date of 20 April 2017)
- Percentage of Participants With Secondary Primary Malignancies During the Course of the Trial(The date when the first consent form was signed to the last date of AE data collection; up to the date of the final data analysis date of 30 November 2016; 7 years and 19 days)
- Time to Onset of Secondary Primary Malignancies(The date when the first consent form was signed to the last date of AE data collection; up to the date of the final data analysis date of 30 November 2016; 7 years and 19 days)