This randomized phase III trial studies how well crizotinib works in treating patients with stage IB-IIIA non-small cell lung cancer that has been removed by surgery and has a mutation in a protein called anaplastic lymphoma kinase (ALK). Mutations, or changes, in ALK can make it very active and important for tumor cell growth and progression. Crizotinib may stop the growth of tumor cells by blocking the ALK protein from working. Crizotinib may be an effective treatment for patients with non-small cell lung cancer and an ALK fusion mutation.
PRIMARY OBJECTIVES: I. To evaluate whether adjuvant therapy with crizotinib will result in improved overall survival (OS) for patients with stage IB \>= 4 cm, II and IIIA, ALK-positive non-small cell lung cancer (NSCLC) following surgical resection. SECONDARY OBJECTIVES: I. To evaluate and compare disease-free survival (DFS) associated with crizotinib. II. To evaluate the safety profile of crizotinib when given in the adjuvant therapy setting. III. To collect tumor tissue and blood specimens for future research. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM A: Patients receive crizotinib orally (PO) twice daily (BID) on days 1-21. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. ARM B: Patients undergo observation. After completion of study treatment, patients are followed up every 6 months if \< 4 or 5 years from study entry, and every 12 months if 5-10 or 6-10 years from study entry.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
166
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, United States
Southern Cancer Center PC-Daphne
Daphne, Alabama, United States
Southern Cancer Center PC-Mobile
Mobile, Alabama, United States
Southern Cancer Center PC-Providence
Mobile, Alabama, United States
Southern Cancer Center PC-Springhill
Mobile, Alabama, United States
Overall survival (OS)
Distribution will be estimated using the Kaplan-Meier method, and Cox proportional hazards models will be used to estimate the treatment hazard ratios. The primary comparison will use a logrank test stratified on the randomization stratification factors with a one-sided type I error rate of 5%. Other comparisons of groups will be made using the logrank test and Cox modeling. Estimate will be accompanied by the corresponding 90% confidence intervals.
Time frame: The time from randomization to death from any cause, assessed up to 10 years
Disease free survival (DFS)
Distribution will be estimated using the Kaplan-Meier method, and Cox proportional hazards models will be used to estimate the treatment hazard ratios. Estimate will be accompanied by the corresponding 90% confidence intervals.
Time frame: The time from randomization to the earliest event defined as: disease recurrence confirmed by biopsy, any new lung cancer (even in the opposite lung) confirmed by biopsy, or death from any cause at any known point in time, assessed up to 10 years
Toxicity rates, determined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Toxicity rates will be compared using Fisher?s exact tests with a one-sided type I error rate of 5%; multivariable logistic regression modeling will be used to adjust for the effect of any covariates that are associated with these categorical outcomes.
Time frame: Up to 10 years
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