Randomized, Multicenter, Phase III, Open-Label Study of Alectinib Versus Pemetrexed or Docetaxel in Anaplastic Lymphoma Kinase-Positive Advanced Non Small Cell Lung Cancer Patients Previously Treated With Platinum-Based Chemotherapy and Crizotinib
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 119
- 试验地点
- 54
- 主要终点
- Progression-Free Survival (PFS) Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by Investigator
研究概览
简要总结
This randomized active-controlled multicenter Phase III open-label study will evaluate and compare between treatment groups the efficacy of alectinib versus chemotherapy in participants with ALK-positive advanced NSCLC who were previously treated with chemotherapy and crizotinib, as measured by investigator-assessed progression-free survival (PFS) and to evaluate and compare between treatment groups the central nervous system (CNS) objective response rate (C-ORR) in participants with measurable CNS metastases at baseline, as assessed by an Independent Review Committee (IRC).
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
- 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 or cytologically confirmed diagnosis of advanced or recurrent (Stage IIIB not amenable for multimodality treatment) or metastatic (Stage IV) NSCLC that is ALK-positive. ALK positivity must have been determined by a validated fluorescence in situ hybridization (FISH) test (recommended probe, Vysis ALK Break-Apart Probe) or a validated immunohistochemistry (IHC) test (recommended antibody, clone D5F3)
- •Participant had received two prior systemic lines of therapy, which must have included one line of platinum-based chemotherapy and one line of crizotinib
- •Prior CNS or leptomeningeal metastases allowed if asymptomatic
- •Participants with symptomatic CNS metastases for whom radiotherapy is not an option will be allowed to participate in this study
- •Measurable disease by RECIST Version 1.1 prior to the administration of study treatment
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- •For all females of childbearing potential, a negative pregnancy test must be obtained within 3 days before starting study treatment
排除标准
- •Participants with a previous malignancy within the past 3 years are excluded (other than curatively treated basal cell carcinoma of the skin, early gastrointestinal [GI] cancer by endoscopic resection or in situ carcinoma of the cervix)
- •Participants who have received any previous ALK inhibitor other than crizotinib
- •Any GI disorder that may affect absorption of oral medications
研究组 & 干预措施
Alectinib
Participants will receive oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food until disease progression, unacceptable toxicity, withdrawal of consent or death.
干预措施: Alectinib (Drug)
Premetrexed/Docetaxel
Participants will receive chemotherapy with either pemetrexed (500 milligrams per square meter [mg/m^2] of body surface area) or docetaxel (75 mg/m^2) intravenously.
干预措施: Docetaxel (Drug)
Premetrexed/Docetaxel
Participants will receive chemotherapy with either pemetrexed (500 milligrams per square meter [mg/m^2] of body surface area) or docetaxel (75 mg/m^2) intravenously.
干预措施: Pemetrexed (Drug)
结局指标
主要结局
Progression-Free Survival (PFS) Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by Investigator
时间窗: Randomization to first documented disease progression, death from any cause, or study end (up to 33 months)
PFS was defined as the time from randomization to the first documented disease progression, as determined using RECIST v1.1, or death from any cause, whichever occurred first. As per RECIST v1.1, disease progression is a 20% increase in the sum of the diameters of target lesions, an increase in size of measurable lesions by at least 5 millimeter (mm) and the appearance of new lesions.
次要结局
- Percentage of Participants With CNS Objective Response Rate (ORR) With Measurable CNS Metastases at Baseline Using RECIST Version 1.1 as Assessed By IRC(Baseline through study end (up to 33 months))
- PFS Using RECIST Version 1.1 as Assessed by IRC(Approximately 15 months (Tumor assessments at baseline, every 6 weeks until progressive disease (PD), death or withdrawal from study prior to PD))
- Percentage of Participants With Objective Response of CR or PR Using RECIST Version 1.1 as Assessed by Investigator and IRC(Approximately 15 months (Tumor assessments at baseline, every 6 weeks until progressive disease (PD), death or withdrawal from study prior to PD))
- Percentage of Participants With Disease Control Using RECIST Version 1.1 as Assessed by Investigator and IRC(Approximately 15 months (Tumor assessments at baseline, every 6 weeks until progressive disease (PD), death or withdrawal from study prior to PD))
- Duration of Response (DOR) Using RECIST Version 1.1 as Assessed by Investigator and IRC(From the first documented CR or PR to the first documented disease progression, death, or study end (up to 33 months))
- PFS in C-ITT Population Using RECIST Version 1.1 as Assessed by Investigator and IRC(Approximately 15 months (Tumor assessments at baseline, every 6 weeks until progressive disease (PD), death or withdrawal from study prior to PD))
- Time to CNS Progression in C-ITT Population Using RECIST Version 1.1 as Assessed by IRC(Approximately 15 months (Tumor assessments at baseline, every 6 weeks until progressive disease (PD), death or withdrawal from study prior to PD))
- Plasma Concentration of Alectinib(Predose (2 hours) at Baseline, Week 3 and Week 6)
- Plasma Concentration of Alectinib Metabolite(Predose (2 hours) at Baseline, Week 3 and Week 6)
- Percentage of Participants With Disease Control in C-ITT Population Using RECIST Version 1.1 as Assessed by IRC(From first documented CR, PR, or SD lasting at least 5 weeks through study end (up to 33 months))
- Percentage of Participants With ORR in C-ITT Population Using RECIST Version 1.1 as Assessed by IRC(Baseline through study end (up to 33 months))
- Duration of Response for Lesions in the CNS (C-DOR) Using RECIST Version 1.1 as Assessed by IRC(From the first documented CR or PR to the first documented disease progression, death, or study end (up to 33 months))
- Overall Survival (OS)(Randomization to death from any cause, through study end (up to 33 months))
- Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time(Baseline through Week 138)
- Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time(Baseline through Week 138)
- Compliance of European Quality of Life (EuroQoL) 5 Dimension 5 Levels (EQ-5D-5L) Questionnaire Over Time(Baseline through Week 60)
- Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC13 Score for ITT Population(Baseline through study end (up to 33 months))
- Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC13 Score for C-ITT Population(Baseline through study end (up to 33 months))
- Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC30 Score for ITT Population(Baseline through study end (up to 33 months))
- Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC30 Score for C-ITT Population(Baseline through study end (up to 33 months))
- TTD in Composite of Three Symptoms (Cough, Dyspnea, and Chest Pain) Using EORTC QLQ-LC13 Score for C-ITT Population(Baseline through study end (up to 33 months))
- TTD in Composite of Three Symptoms (Cough, Dyspnea, and Chest Pain) Using EORTC QLQ-LC13 Score for ITT Population(Baseline through study end (up to 33 months))
- Percentage of Participants With Adverse Events (AEs)(Baseline through study end (up to 33 months))