A Phase I/II Study of the ALK Inhibitor CH5424802/ RO5424802 in Patients With ALK-Rearranged Non-Small Cell Lung Cancer Previously Treated With Crizotinib
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 134
- 试验地点
- 42
- 主要终点
- Number of Participants With Dose Limiting Toxicities (DLTs): Phase I
研究概览
简要总结
This non-randomized, open-label, multicenter study will evaluate the safety and efficacy of alectinib in participants with ALK-rearranged non-small cell lung cancer who failed crizotinib treatment. In Phase I, cohorts of participants will receive escalating doses of alectinib orally twice daily. In Phase II, patients who failed crizotinib treatment will receive the recommended phase II dose.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed, locally advanced, not amenable to curative therapy, or metastatic NSCLC
- •ALK-rearrangement confirmed by the Food and Drug Administration (FDA) approved test
- •NSCLC that has failed crizotinib treatment
- •Measurable disease as defined by RECIST v1.1
- •Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to (<=) 2
- •Adequate hematologic, hepatic and renal function
排除标准
- •Prior therapy with ALK inhibitor other than crizotinib
- •Brain or leptomeningeal metastases that are symptomatic and/or requiring treatment
- •History of serious cardiac dysfunction
- •History of or current active infection with hepatitis B, hepatitis C or human immunodeficiency virus (HIV)
- •Clinically significant gastrointestinal abnormality that would affect absorption of the drug
- •Pregnant or lactating women
研究组 & 干预措施
Alectinib: Phase I (Dose Escalation)
Participants will receive escalating doses of alectinib capsules orally until disease progression, death or withdrawal for any other reasons.
干预措施: Alectinib (Drug)
Alectinib (Phase II: RP2 dose)
Participants will receive recommended Phase II dose as determined from Phase I until disease progression, death or withdrawal for any other reasons.
干预措施: Alectinib (Drug)
结局指标
主要结局
Number of Participants With Dose Limiting Toxicities (DLTs): Phase I
时间窗: Throughout Cycle 1 of Phase I (21 days)
The DLTs were defined as any which included Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with bleeding or Grade 4 neutropenia continuing for greater than equal to (\>=) 7 consecutive days, non-hematological toxicity of Grade 3 or higher (excluding transient electrolyte abnormalities, diarrhea, nausea, and vomiting that recovers to Grade 2 or lower with appropriate treatment and participants having Grade 2 aspartate transaminase (AST) and/or alanine transaminase (ALT) at baseline must have Grade 3 AST/ALT for 7 days or Grade 4 AST/ALT to be considered a DLT), and adverse events (AEs) that required suspension of treatment for a total of \>=7 days which the Investigator could not rule out as been related to alectinib.
Recommended Phase II Dose (RP2D): Phase I
时间窗: Throughout Cycle 1 of Phase I (21 days)
RP2D was defined as the highest dose with acceptable toxicity as determined from Phase I of the study.
Percentage of Participants With Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) by Independent Review Committee (IRC): Phase II
时间窗: Cycle 1 Day 1 up to 194 weeks (assessed at every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter) (1 cycle = 21 days)
Percentage of participants with objective response as assessed by IRC was defined as the percentage of responders in the response evaluable population, where responders were defined as participants determined to have a best overall response of complete response (CR) or partial response (PR) based on the RECIST v1.1 criteria. CR: disappearance of all target and non-target lesions (TLs) and normalization of tumor markers. Pathological lymph nodes must have short axis measures less than (\<) 10 millimeter (mm). PR: at least a 30 percent (%) decrease in the sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of TLs, taking as reference the baseline sum of diameters. CR and PR were to be confirmed by repeat assessments \>=4 weeks after initial documentation. Clopper-Pearson method was used to calculate 95% confidence interval (CI).
次要结局
- Percentage of Participants With Objective Response According to RECIST v1.1 by Investigator: Phase I(Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days))
- Duration of Response (DOR) According to RECIST v1.1 by Investigator: Phase I(Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days))
- Percentage of Participants With Objective Response According to RECIST v1.1 by Investigator: Phase II(Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days))
- Percentage of Participants With Disease Control According to RECIST v1.1 by Investigator: Phase II(Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days))
- Percentage of Participants With Disease Progression According to RECIST v1.1 by IRC or Death : Phase II(Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days))
- Progression-Free Survival (PFS) According to RECIST v1.1 by IRC: Phase II(Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days))
- Percentage of Participants With Disease Progression According to RECIST v1.1 by Investigator or Death : Phase II(Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days))
- PFS According to RECIST v1.1 by Investigator: Phase II(Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days))
- Percentage of Participants Who Died Due to Any Cause: Phase II(Baseline up to death (any cause) (maximum follow up 284 weeks))
- Overall Survival (OS) Time: Phase II(Baseline up to death (any cause) (maximum follow up 284 weeks))
- DOR According to RECIST v1.1 by IRC: Phase II(Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days))
- DOR According to RECIST v1.1 by Investigator: Phase II(Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days))
- Percentage of Participants With Central Nervous System Objective Response (COR) According to RECIST v1.1 by IRC: Phase II(Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days))
- Percentage of Participants With COR According to Response Assessment in Neuro-Oncology (RANO) Criteria by IRC: Phase II(Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days))
- CNS Duration of Response (CDOR) According to RECIST v1.1 by IRC: Phase II(Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days))
- CDOR According to RANO Criteria by IRC: Phase II(Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days))
- Percentage of Participants With CNS Progression According to RECIST v1.1 by IRC: Phase II(Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days))
- Percentage of Participants With CNS Progression According to RANO Criteria by IRC: Phase II(Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days))
- Maximum Observed Plasma Concentration (Cmax) After Single Dose of Alectinib: Phase I(Pre-dose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 24, 32 and 48 hours post-dose on Cycle 1 Day -3 (1 cycle = 21 days))
- Cmax After Multiple Dose of Alectinib: Phase I(Pre-dose (0 hour), 0.5, 1, 2, 4, 6, 8 and 10 hours post-dose on Cycle 2 Day 1 (1 cycle = 21 days))
- Area Under the Plasma Concentration (AUC) Versus Time Curve Extrapolated to Infinity (AUCinf) After Single Dose of Alectinib: Phase I(Pre-dose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 24, 32 and 48 hours post-dose on Cycle 1 Day -3 (1 cycle = 21 days))
- AUC From Time Zero to Last Measurable Concentration (AUClast) After Multiple Dose of Alectinib: Phase I(Pre-dose (0 hour), 0.5, 1, 2, 4, 6, 8 and 10 hours post-dose on Cycle 2 Day 1 (1 cycle = 21 days))
- Ctrough After Multiple Dose of Alectinib: Phase II(Pre-dose (0 hour) on Day 1 of Cycles 2, Cycle 3, Cycle 4, Cycle 5 (1 cycle = 21 days))
- Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30): Phase II(Baseline, Weeks 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69, 72, 75, 78, 81, 84, 87, 90, 93, 96, 99, 105, 111, 117, last visit (up to 194 weeks))
- Change From Baseline in EORTC Quality of Life Questionnaire Lung Cancer 13 (EORTC QLQ-LC13): Phase II(Baseline, Weeks 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69, 72, 75, 78, 81, 84, 87, 90, 93, 96, 99, 105, 111, 117, last visit (up to 194 weeks))