This randomized, multicenter, Phase III, open-label study will evaluate the efficacy and safety of alectinib versus crizotinib and to evaluate the pharmacokinetics of alectinib in asian participants with treatment-naive ALK-positive advanced NSCLC. Participants will be randomized 2:1 into one of the two treatment groups to receive either alectinib (600 milligrams \[mg\] twice daily \[BID\]) or crizotinib (250 mg BID) orally, respectively.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
187
Alectinib capsules will be administered orally at a dose of 600 mg BID until disease progression, unacceptable toxicity withdrawal of consent, or death.
Crizotinib capsules will be administered orally at a dose of 250 mg BID until disease progression, unacceptable toxicity withdrawal of consent, or death.
Beijing Cancer Hospital
Beijing, China
Beijing Chest Hospital
Beijing, China
the First Hospital of Jilin University
Changchun, China
Jilin Cancer Hospital
Changchun, China
West China Hospital, Sichuan University
Chengdu, China
Sun Yet-sen University Cancer Center
Guangzhou, China
Guangdong General Hospital
Guangzhou, China
The First Affiliated Hospital of Guangzhou Medical University
Guangzhou, China
The First Affiliated Hospital of College of Medicine, Zhejiang University
Hangzhou, China
Zhejiang Cancer Hospital
Hangzhou, China
...and 11 more locations
Progression-Free Survival (PFS) as Determined by Investigator Using Response Evaluation Criteria in Solid Tumor (RECIST) v1.1
PFS was defined as the time (in months) from randomization to the first documentation of disease progression, as determined by the investigators, or to death from any cause, whichever occurred first.
Time frame: From the date of randomization to the date of the first documented disease progression or death, whichever occurred first (up to overall period of approximately 40 months)
PFS as Determined by Independent Review Committee (IRC) Using RECIST v1.1
PFS was defined as the time (in months) from randomization to the first documentation of disease progression, as determined by an independent review committee, or to death from any cause, whichever occurred first.
Time frame: Baseline, Week 8, thereafter every 8 weeks until disease progression, death or withdrawal from the study and 4 weeks after permanent discontinuation (up to overall period of approximately 40 months)
Percentage of Participants With Objective Response of Complete Response (CR) or Partial Response (PR) as Determined by Investigator Using RECIST v1.1
Time frame: Baseline, Week 8, thereafter every 8 weeks until disease progression, death or withdrawal from the study and 4 weeks after permanent discontinuation (up to overall period of approximately 40 months)
Time to Progression of Disease in the CNS as Determined by IRC Using RECIST v1.1
Time frame: Baseline, Week 8, thereafter every 8 weeks until disease progression, death or withdrawal from the study and 4 weeks after permanent discontinuation (up to overall period of approximately 40 months)
Time to Progression of Disease in the CNS as Determined by IRC Using Response Assessment in Neuro-Oncology (RANO)
Time frame: Baseline, Week 8, thereafter every 8 weeks until disease progression, death or withdrawal from the study and 4 weeks after permanent discontinuation (up to overall period of approximately 40 months)
Duration of Response (DOR) Assessed by Investigator Using RECIST v1.1
Time frame: Baseline, Week 8, thereafter every 8 weeks until disease progression, death or withdrawal from the study and 4 weeks after permanent discontinuation (up to overall period of approximately 40 months)
Overall Survival Time
Time frame: Baseline, until death (up to overall period of approximately 40 months)
Percentage of Participants With Non-serious Adverse Events and Serious Adverse Events
An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
Time frame: Up to overall period of approximately 40 months
Time to Deterioration Assessed Using EORTC Quality of Life Questionnaire-Core (QLQ-C30) Score
Time frame: Baseline, Week 4, thereafter every 4 weeks until disease progression, death or withdrawal from the study and 4 weeks after permanent discontinuation (up to overall period of approximately 40 months)
Time to Deterioration Assessed Using EORTC Quality of Life Questionnaire-Lung Cancer Module (QLQ-LC13) Score
Time frame: Baseline, Week 4, thereafter every 4 weeks until disease progression, death or withdrawal from the study and 4 weeks after permanent discontinuation (up to overall period of approximately 40 months)
Area Under the Plasma Concentration-time Curve (AUC) of Alectinib and Its Metabolite
AUC was collected for both alectinib and its major metabolite, M4, and was based on their concentrations in plasma over time.
Time frame: Baseline and Week 4 predose (within 2 hours before administration of study drug)
Maximum Plasma Concentration Observed (Cmax) of Alectinib and Its Metabolite
Cmax was collected for both alectinib and its major metabolite, M4, and was based on their concentrations in plasma over time.
Time frame: Baseline and Week 4 predose (within 2 hours before administration of study drug)
Time to Cmax (Tmax) of Alectinib and Its Metabolite
Tmax was collected for both alectinib and its major metabolite, M4, and was based on their concentrations in plasma over time.
Time frame: Baseline and Week 4 predose (within 2 hours before administration of study drug)
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