A Randomized Phase III, Double-blind, Placebo-controlled, Multi-center Study to Evaluate the Efficacy and Safety of Everolimus (RAD001) in Adult Patients With Advanced Hepatocellular Carcinoma After Failure of Sorafenib Treatment - The EVOLVE-1 Study
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 546
- 试验地点
- 20
- 主要终点
- Overall Survival (OS)
研究概览
简要总结
The purpose of this study is to compare treatment with RAD001 plus best supportive care (BSC) to placebo plus BSC in patients with advanced HCC whose disease progressed while on or after sorafenib treatment or who are intolerant to sorafenib.
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
- All
- 接受健康志愿者
- 否
入选标准
- •Advanced liver cancer
- •Prior systemic treatment with sorafenib for advanced HCC and for whom their disease progressed during or after sorafenib treatment, or were intolerant to sorafenib treatment. Specifically, this can be defined as:
- •Documented radiological confirmation (radiology scans or report) of disease progression during or after sorafenib treatment
- •Intolerance to sorafenib (at any dose and/or duration) is defined as documented sorafenib-related grade 3 or 4 adverse events that led to sorafenib discontinuation.
- •Sorafenib must be the last antineoplastic treatment before randomization
- •Prior local and/or hormonal therapy (e.g., tamoxifen) before sorafenib is allowed
- •One systemic chemotherapy regimen for advanced HCC is allowed before sorafenib treatment
- •ECOG performance status of ≤ 2
- •Child-Pugh A
排除标准
- •Active bleeding during the last 28 days
- •Prior therapy with mTOR inhibitors
- •Prior liver or other organ transplantation which mandates systemic immunosuppression
- •Other protocol-defined inclusion/exclusion criteria may apply
研究组 & 干预措施
Everolimus + Best Supportice Care (BSC)
Patients were assigned to the Everolimus + BSC arm in a ratio of 2:1 over the Placebo arm. Everolimus was taken as a daily oral dose of 7.5 mg and was defined as the investigational drug. In addition to taking Everolimus, all patients also received BSC as per normal local practice.
干预措施: Everolimus (Drug)
Everolimus + Best Supportice Care (BSC)
Patients were assigned to the Everolimus + BSC arm in a ratio of 2:1 over the Placebo arm. Everolimus was taken as a daily oral dose of 7.5 mg and was defined as the investigational drug. In addition to taking Everolimus, all patients also received BSC as per normal local practice.
干预措施: Best Supportive Care (BSC) (Other)
Placebo + Best Supportive Care
Placebo Everolimus was taken as a daily oral dose of 7.5 mg and was defined as the control drug. In addition to taking Placeb Everolimus, all patients also received BSC as per normal local practice.
干预措施: Everolimus Placebo (Drug)
Placebo + Best Supportive Care
Placebo Everolimus was taken as a daily oral dose of 7.5 mg and was defined as the control drug. In addition to taking Placeb Everolimus, all patients also received BSC as per normal local practice.
干预措施: Best Supportive Care (BSC) (Other)
结局指标
主要结局
Overall Survival (OS)
时间窗: When 454 OS events were observed
OS was defined as the time from the date of randomization to the date of death from any cause. The comparison of OS between the 2 arms was done using a stratified log-rank test at one-sided 2.5% level of significance.
次要结局
- Time to Tumor Progression (TTP)(Until all patients have disease progression or leave study due to intolerable adverse events- Estimate of 1 year for each patient)
- Percentage of Participants With Disease Control Rate (DCR)(Until all patients have disease progression or leave study due to intolerable adverse events- Estimate of 1 year for each patient)
- Time to Definitive Deterioration of ECOG Performance Score (PS) Score(Until all patients have disease progression or leave study due to intolerable adverse events- Estimate of 1 year for each patient.)
- Time to Definitive Deterioration of EORTC QLQ-C30 Scores(Until all patients have disease progression or leave study due to intolerable adverse events - Estimate of 1 year for each patient.)
- Pharmacokinetics Assessments - Cmin(Until all patients have disease progression or leave study due to intolerable adverse events - Estimate of 1 year for each patient.)
- Pharmacokinetics Assessments - Cmax(Until all patients have disease progression or leave study due to intolerable adverse events- Estimate of 1 year for each patient.)