A Randomized Phase III Trial for Surgically Resected Early Stage Non-Small Cell Lung Cancer: Crizotinib versus Observation for Patients with Tumors Harboring the Anaplastic Lymphoma Kinase (ALK) Fusion Protein
The purpose of this research study is to compare any good and bad effects of using the study
drug, crizotinib (also known as XALKORI), after completion of surgery and, in some cases,
after chemotherapy and/or radiation therapy for ALK-positive non-small cell lung cancer.
1 Primary Objective:
To evaluate whether adjuvant therapy with crizotinib will result in improved Overall Survival (OS) over placebo for patients with stage IB >/= 4cm, II and IIIA, ALK-positive NSCLC following surgical resection.
2 Secondary Objectives:
2.1 To evaluate and compare Disease-free Survival (DFS) associated with crizotinib and placebo.
2.2 To evaluate the safety profile of crizotinib when given in the adjuvant therapy setting.
2.3 To collect tumor tissue and blood specimens for future research.
Participants must have undergone complete surgical resection of their stage IIA, IIB, IIIA or IIIB non-squamous or squamous b NSCLC per American Joint Committee on Cancer (AJCC) 7th edition and have had negative margins; N3 disease is not allowed.
Baseline chest computed tomography (CT) must be performed within 3 months (90 days) prior to randomization to ensure no evidence of disease; if clinically indicated additional imaging studies must be performed to rule out metastatic disease.
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
Must be registered to the ALCHEMIST-SCREEN (ALLIANCE A151216) trial prior to randomization.
Positive for translocation or inversion events involving the ALK gene locus (e.g. resulting in echinoderm microtubule associated protein like 4 [EML4]-ALK fusion) as determined by the Vysis Break Point fluorescence in situ hybridization (FISH) assay and defined by an increase in the distance between 5' and 3' ALK probes or the loss of the 5' probe; this must have been performed: By a local Clinical Laboratory Improvement Amendments (CLIA) certified laboratory: Report must indicate the results as well as the CLIA number of the laboratory which performed the assay; tissue must be available for submission for central, retrospective confirmation of the ALK fusion status via ALCHEMIST-SCREEN (ALLIANCE A151216) OR; Patient registered to and the ALK fusion status performed centrally on the ALCHEMIST-SCREEN (ALLIANCE A151216).
Women must not be pregnant or breast-feeding; all females of childbearing potential must have a blood or urine pregnancy test within 72 hours prior to randomization to rule out pregnancy.
Women of childbearing potential and sexually active males must be strongly advised to practice abstinence or use an accepted and effective method of contraception.
Must NOT have uncontrolled intercurrent illness including, but not limited to, serious ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
No known interstitial fibrosis or interstitial lung disease.
No prior treatment with crizotinib or another ALK inhibitor.
No ongoing cardiac dysrhythmias of grade >= 2 National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, uncontrolled atrial fibrillation (any grade), or corrected QT (QTc) interval > 470 msec.
No use of medications, herbals, or foods that are known potent cytochrome P450, subfamily 3A, polypeptide 4 (CYP3A4) inhibitors or inducers, included but not limited to those outlined.
Must be adequately recovered from surgery at the time of randomization.
The minimum time requirement between date of surgery and randomization must be at least 4 weeks (28 days).
The maximum time requirement between surgery and randomization must be: 3 months (90 days) if no adjuvant chemotherapy was administered; 6 months (180 days) if adjuvant chemotherapy was administered; 8 months (240 days) if adjuvant chemotherapy and radiation therapy were administered.
Must have completed any prior chemotherapy or radiation therapy 2 or more weeks (6 or more weeks for mitomycin and nitrosoureas) prior to randomization and be adequately recovered at the time of randomization NOTE: Patients taking low dose methotrexate for non-malignant conditions and other cytotoxic agents for non-malignant conditions are allowed to continue treatment while on study.
Adequate organ and bone marrow function.
Prior to randomization patients with any non-hematologic toxicity from surgery, chemotherapy, or radiation must have recovered to grade ≤ 1 with the exception of alopecia and the criteria outlined.
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