Randomized, Double-Blind, Phase 2/3 Study in Subjects With Malignant Pleural Mesotheliomato Assess ADI-PEG 20 With Pemetrexed and Cisplatin (ATOMIC-Meso Phase 2/3 Study)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 249
- 试验地点
- 44
- 主要终点
- Overall Survival Phase 3 Interim Analysis
研究概览
简要总结
This is a study of ADI-PEG 20 (pegylated arginine deiminase), an arginine degrading enzyme versus placebo in patients with malignant pleural mesothelioma. Malignant pleural mesothelioma have been found to require arginine, an amino acid. Thus the hypothesis is that by restricting arginine with ADI-PEG 20, the malignant pleural mesothelioma cells will starve and die.
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
- Triple (Participant, Care Provider, 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
- •Histologically proven unresectable MPM of biphasic or sarcomatoid histology
- •Naïve to chemotherapy or immunotherapy
- •ECOG PS 0-1
- •Expected survival of at least 3 months
- •Age 18 years or over (there is no upper age limit)
- •Measurable disease by modified RECIST criteria for MPM for local pleural disease and RECIST 1.1 criteria for metastatic lesions
- •Written (signed and dated) informed consent and must be capable of co-operating with treatment and follow up
- •Adequate hematologic, hepatic, and renal function
排除标准
- •Radiotherapy (except for palliative reasons) in the previous two weeks before study treatment
- •History of unstable cardiac disease
- •Ongoing toxic manifestations of previous treatments
- •Symptomatic brain or spinal cord metastases (patients must be stable for > 1 month post radiotherapy or surgery)
- •Major thoracic or abdominal surgery from which the patient has not yet recovered.
研究组 & 干预措施
Drug: ADI-PEG 20 plus Pem Platinum
Dose: 36 mg/m2 given weekly Route of Administration: Intramuscular (IM) Duration : Course of Study
In Combination With:
Pemetrexed Dose: 500 mg/m2 every 3 weeks Route of Administration: Intravenous Cisplatin Dose: 75 mg/m2 every 3 weeks Route of Administration: Intravenous Carboplatin Dose: AUC 5 mg/mL/min every 3 weeks Route of Administration: Intravenous
ADI-PEG 20 plus Pem Platinum: Investigational Drug in combination approved standard of care treatment for this indication
干预措施: ADI-PEG 20 plus Pem Platinum (Drug)
Drug: Placebo plus Pem Platinum
Dose: 36 mg/m2 given weekly Route of Administration: Intramuscular (IM) Duration : Course of Study
In Combination With:
Pemetrexed Dose: 500 mg/m2 every 3 weeks Route of Administration: Intravenous Cisplatin Dose: 75 mg/m2 every 3 weeks Carboplatin Dose: AUC 5 mg/mL/min every 3 weeks Route of Administration: Intravenous
Placebo plus Pem Platinum: Placebo in combination approved standard of care treatment for this indication
干预措施: Placebo plus Pem Platinum (Other)
结局指标
主要结局
Overall Survival Phase 3 Interim Analysis
时间窗: Approximately 18 months
The primary analysis of OS Phase 3 was performed at the interim analysis. This was performed once 50% of the planned OS events for phase 3 have occurred (ie, 169 of the 338 planned OS events). This interim analysis will evaluate OS in the ITT population in an unblinded manner. The OS data at the second interim analysis will be analyzed to support the following decisions: Futility stopping: Terminate the study due to futility at the interim analysis. Sample size re-estimation: Increase the target number of OS events after the second interim analysis.. The treatment effect on OS will be evaluated using the stratified log-rank test (stratified by tumor histology).
Response Rate
时间窗: approximately 18 months
Objective Response Rate is calculated as the proportion of subjects whose best tumor response from all post-baseline tumor assessments is complete response (CR) or partial response (PR). The best tumor response is the best response recorded from the start of the treatment until the end of treatment taking into account any requirement for confirmation. To test Objective Response Rate significance, a Relative Risk Ratio (ADI-PEG 20 / Placebo) was calculated as the common relative risk of having a response (CR or PR) based on the Mantel-Haenszel estimator controlling for tumor histology (biphasic versus sarcomatoid).
Overall Survival
时间窗: 18 months
Overall survival is defined as the time from randomization until death. In the event that no death was documented prior to study termination or analysis cutoff, OS was censored at the last known date the subject was known to be alive, either through completion of on-study visits or through survival follow-up contact. The treatment effect on OS was evaluated using the stratified log-rank test (stratified by tumor histology). The Kaplan-Meier curves were also plotted. A Cox proportional hazard model with an adjustment for tumor histology (biphasic vs sarcomatoid) was used to compute the estimated hazard ratio and two-sided 95% CI. The treatment effect on OS was evaluated using the stratified log-rank test (stratified by tumor histology). The significance level to be used in the OS analysis at the final analysis was based on α = 0.04999 (two-sided).
次要结局
- Progression Free Survival(approximately 18 months)