A Randomized, Placebo-controlled, Double-blind, Multicenter Phase 2 Study With a Lead in Phase of Erlotinib With or Without SNDX-275 in Patients With NSCLC After Failure In Up to Two Prior Chemotherapeutic Regimens for Advanced Disease
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 141
- 试验地点
- 21
- 主要终点
- Identification of Safe-dose for the Phase 2 Double-blind Phase in the Lead-in Phase
研究概览
简要总结
The purpose of this study is to evaluate the safety and efficacy of entinostat in combination with erlotinib in the treatment of Advanced Non-Small Cell Lung Cancer (NSCLC).
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Lead-in Phase: Erlotinib + Entinostat 10 mg
Erlotinib 150 mg tablets, orally, daily plus entinostat 10 mg, tablets, orally, on Days 1 and 15 of each 28-day cycle until disease progression or intolerable toxicities for up to 6 cycles in the Lead-in Phase.
干预措施: Erlotinib (Drug)
Lead-in Phase: Erlotinib + Entinostat 5 mg
Erlotinib 150 mg, tablets, orally, daily plus entinostat 5 mg, tablets, orally, on Days 1 and 15 of each 28-day cycle until disease progression or intolerable toxicities for up to 6 cycles in the Lead-in Phase.
干预措施: Entinostat (Drug)
Lead-in Phase: Erlotinib + Entinostat 5 mg
Erlotinib 150 mg, tablets, orally, daily plus entinostat 5 mg, tablets, orally, on Days 1 and 15 of each 28-day cycle until disease progression or intolerable toxicities for up to 6 cycles in the Lead-in Phase.
干预措施: Erlotinib (Drug)
Lead-in Phase: Erlotinib + Entinostat 10 mg
Erlotinib 150 mg tablets, orally, daily plus entinostat 10 mg, tablets, orally, on Days 1 and 15 of each 28-day cycle until disease progression or intolerable toxicities for up to 6 cycles in the Lead-in Phase.
干预措施: Entinostat (Drug)
Double-blind Phase: Erlotinib + Entinostat 10 mg
Erlotinib 150 mg, tablets, orally, daily plus entinostat 10 mg, tablets, orally, on Day 1 and 15 of a 28-day cycle until disease progression or intolerable toxicities for up to 6 cycles in the Double-blind Phase.
干预措施: Entinostat (Drug)
Double-blind Phase: Erlotinib + Entinostat 10 mg
Erlotinib 150 mg, tablets, orally, daily plus entinostat 10 mg, tablets, orally, on Day 1 and 15 of a 28-day cycle until disease progression or intolerable toxicities for up to 6 cycles in the Double-blind Phase.
干预措施: Erlotinib (Drug)
Double-blind Phase: Erlotinib + Placebo
Erlotinib 150 mg, tablets, orally, daily plus placebo matching entinostat, tablets, orally, on Days 1 and 15 of each 28-day cycle until disease progression or intolerable toxicities for up to 6 cycles in the Double-blind Phase.
干预措施: Placebo (Drug)
Double-blind Phase: Erlotinib + Placebo
Erlotinib 150 mg, tablets, orally, daily plus placebo matching entinostat, tablets, orally, on Days 1 and 15 of each 28-day cycle until disease progression or intolerable toxicities for up to 6 cycles in the Double-blind Phase.
干预措施: Erlotinib (Drug)
Crossover Phase: Erlotinib + Entinostat 10 mg
Participants in the Double-blind Phase Erlotinib + Placebo arm who experienced disease progression crossed over to receive open-label erlotinib 150 mg, tablets, orally, daily plus entinostat 10 mg, tablets, orally, on Days 1 and 15 of each 28-day cycle until disease progression or intolerable toxicities.
干预措施: Entinostat (Drug)
Crossover Phase: Erlotinib + Entinostat 10 mg
Participants in the Double-blind Phase Erlotinib + Placebo arm who experienced disease progression crossed over to receive open-label erlotinib 150 mg, tablets, orally, daily plus entinostat 10 mg, tablets, orally, on Days 1 and 15 of each 28-day cycle until disease progression or intolerable toxicities.
干预措施: Erlotinib (Drug)
结局指标
主要结局
Identification of Safe-dose for the Phase 2 Double-blind Phase in the Lead-in Phase
时间窗: Cycle 1 of Lead-in Phase
Safe recommended Phase 2 dose was determined based on dose-limiting toxicities (DLT) in Cycle 1. A DLT was defined as any of the following occurring in Cycle 1: Grade 3 or greater nonhematologic toxicity that was considered related to either entinostat or erlotinib or a Grade 4 hematologic toxicity lasting more than 7 days and/or resulting in a dose delay. Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 scale was used where Grade 1=mild, Grade 2=Moderate, Grade 3=Severe, medically significant, Grade 4=life-threatening and 5=death. The dose that was found to be safe is reported.
4-Month Progression-free Survival (PFS) Rate in the Double-blind Phase
时间窗: Month 4
PFS rate at 4 months was defined as the percentage of participants who are progression-free at 4 months.
次要结局
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) by Severity in the Double-blind Phase(First dose of study drug to within 30 days past last dose (Up to 7 months))
- Tmax: Time to Cmax of Entinostat in the Lead-in Phase(Day 1 predose and 0.5, 1, 2, 4 and 6 hours after dose; Days 2 and 8 predose (entinostat alone); Day 15 predose and 0.5, 1, 2, 4, 6 and 24 hours after dose)
- AUC(0-last): Area Under the Concentration-time Curve From Time 0 to Last Quantifiable Concentration in the Lead-in Phase(Day 1 predose and 0.5, 1, 2, 4 and 6 hours after dose; Days 2 and 8 predose (entinostat alone); Day 15 predose and 0.5, 1, 2, 4, 6 and 24 hours after dose)
- Objective Response Rate (ORR) in the Double-blind Phase(Month 6)
- 6-Month PFS Rate in the Double-blind Phase(Month 6)
- Vital Sign Values: Heart Rate in the Double-blind Phase(Day 1 and 15 of each cycle to safety follow-up 30 days past last dose (up to 7 months))
- Vital Sign Values: Respiration Rate in the Double-blind Phase(Day 1 and 15 of each cycle to safety follow-up 30 days past last dose (up to 7 months))
- Vital Sign Values: Weight in the Double-blind Phase(Day 1 and 15 of each cycle to safety follow-up 30 days past last dose (up to 7 months))
- Vital Sign Values: Systolic Blood Pressure in the Double-blind Phase(Day 1 and 15 of each cycle to safety follow-up 30 days past last dose (up to 7 months))
- Vital Sign Values: Diastolic Blood Pressure in the Double-blind Phase(Day 1 and 15 of each cycle to safety follow-up 30 days past last dose (up to 7 months))
- Number of Participants With Grade 3 or 4 Laboratory Variables in the Double-blind Phase(Day 1 and 15 of each cycle to safety follow-up 30 days past last dose (up to 7 months))
- Vital Sign Values: Temperature in the Double-blind Phase(Day 1 and 15 of each cycle to safety follow-up 30 days past last dose (up to 7 months))
- Cmax: Maximum Plasma Concentration of Entinostat in the Lead-in Phase(Day 1 predose and 0.5, 1, 2, 4 and 6 hours after dose; Days 2 and 8 predose (entinostat alone); Day 15 predose and 0.5, 1, 2, 4, 6 and 24 hours after dose)
- AUC(0-24): Area Under the Concentration-time Curve From Time 0 to 24 Hours in the Lead-in Phase(Day 1 predose and 0.5, 1, 2, 4 and 6 hours after dose; Days 2 and 8 predose (entinostat alone); Day 15 predose and 0.5, 1, 2, 4, 6 and 24 hours after dose)