A Phase II, Open-Label, Multi-Arm Study to Determine the Preliminary Efficacy of Novel Combinations of Treatment in Patients With Platinum Refractory Extensive-Stage Small-Cell Lung Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 72
- 试验地点
- 1
- 主要终点
- Number of Participants With Overall Response
研究概览
简要总结
Study design This is a Phase II, open-label, multi-drug, multi-center, multi-arm, signal-searching study in patients with extensive-stage small-cell lung cancer (SCLC) who have refractory or resistant disease from prior platinum-based chemotherapy.
详细描述
This study is modular in design, allowing evaluation of the preliminary efficacy, safety, tolerability, and immunogenicity of novel combinations of immunotherapies and/or deoxyribonucleic acid (DNA) damage repair inhibitors in patients with platinum refractory or resistant extensive-stage-disease SCLC. Patients who have progressive disease (PD) during first-line platinum-based chemotherapy (platinum refractory) or PD within 90 days after completing first-line platinum-based chemotherapy (platinum resistant) will be enrolled to the study. The primary objective of the study is to assess the preliminary efficacy of each treatment arm based on objective response rate (ORR).
This study consists of a number of arms (sub-studies), each evaluating the efficacy, safety, and tolerability of a specific agent or combination. This study was initially open with 2 arms (Arms A and B), and additional arms may open, provided there is compelling rationale for the combination and safe and tolerable doses and schedules have been determined from ongoing Phase I studies. There are 2 pre-defined arms:
A. Durvalumab + tremelimumab followed by durvalumab monotherapy B. AZD1775 + carboplatin (CBDP)
Further arm was added in amendment 3:
C. AZD6738 + olaparib Amendment #4 was updated with possibility to allow expansion of any arm, to a total of 40 eligible subjects, based on Review Committee assessment of data from the first 20 subjects (from Stage 1 and Stage 2). Currently Arm A will enroll 20 additional patients into expansion.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 130 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
ARM A
干预措施: Durvalumab and Tremelimumab (Drug)
ARM B
干预措施: AZD1775 and carboplatin (CBPT) (Drug)
ARM C
干预措施: AZD6738 and olaparib (Drug)
结局指标
主要结局
Number of Participants With Overall Response
时间窗: Until disease progression [PD] (Up to 3.5 Years)
Overall Response Rate (ORR) using Investigator assessments according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1. ORR was defined as the number (percentage) of participants with a confirmed Complete Response (CR) or confirmed Partial Response (PR) and was estimated for each treatment arm with corresponding 2-sided 95% exact confidence intervals (CIs). A confirmed response of CR/PR meant that a response of CR/PR was recorded at one visit and confirmed by repeat imaging, preferably at the next regularly scheduled imaging visit, and not less than 4 weeks after the visit when the response was first observed, with no evidence of progression between the initial and CR/PR confirmation visit.
次要结局
- Duration of Response (DoR)(Until disease progression or data cut-off or Death (Up to 3.5 Years))
- Progression Free Survival (PFS)(Until disease progression or data cut-off or Death (Up to 3.5 Years))
- Time to Maximum Concentration (Tmax)(Cycle 1 (each cycle was 28 days in length) Day 1 (post-dose))
- Partial Area Under the Concentration-time Curve (AUC0-6)(Cycle 1 (each cycle was 28 days in length) Day 1 (post-dose) and Cycle 1 Day 7 (pre-dose and post-dose))
- Percentage of Participants With Disease Control at 12 Weeks(At 12 Weeks)
- Overall Survival (OS)(Until disease progression or data cut-off or Death (Up to 3.5 Years))
- Time to Response (TTR)(Until disease progression or data cut-off or Death (Up to 3.5 Years))
- Area Under the Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUC0-t)(Cycle 1 (each cycle was 28 days in length) Day 1 (post-dose) and Cycle 1 Day 7 (pre-dose and post-dose))
- Time to Maximum Concentration at Steady State (Tmax,ss)(Cycle 1 (each cycle was 28 days in length) Day 7 (pre-dose and post-dose))
- Serum Concentrations of Durvalumab and Tremelimumab(Durvalumab: Cycle 1 (each cycle was 4 weeks) Day 1(post-dose); Cycle 2 Day 1(pre-dose); Cycle 5 Day 1 (pre-dose); Tremelimumab: Cycle 1 (each cycle was 4 weeks) Day 1 (post-dose); Cycle 2 Day 1 (pre-dose); Cycle 5 Day 1 (No dose); Cycle 7 Day 1 (No dose))
- Maximum Concentration (Cmax)(Cycle 1 (each cycle was 28 days in length) Day 1 (post-dose))
- Maximum Concentration at Steady State (Cmax,ss)(Cycle 1 (each cycle was 28 days in length) Day 7 (pre-dose and post-dose))
- Apparent Clearance of Drug at Steady State at Steady State (CLss/F)(Cycle 1 (each cycle was 28 days in length) Day 7 (pre-dose and post-dose))
- Minimum Concentration at Steady State (Cmin,ss)(Cycle 1 (each cycle was 28 days in length) Day 7 (pre-dose and post-dose))
- Area Under the Concentration-time Curve at Steady State (AUCss)(Cycle 1 (each cycle was 28 days in length) Day 7 (pre-dose and post-dose))
- Plasma Concentrations of Adavosertib and Carboplatin(Adavosertib: Cycle 1 (each cycle was 21 days) Day 3 (pre-dose and post-dose); Cycle 3 Day 3 (pre-dose and post-dose); Carboplatin: Cycle 1 (each cycle was 21 days) Day 1 (post-dose))
- Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)(Day 1 until disease progression, and follow-up visit (Up to 3.5 Years))