A Phase III Double-Blind Trial for Surgically Resected Early Stage Non-small Cell Lung Cancer: Crizotinib Versus Placebo for Patients With Tumors Harboring the Anaplastic Lymphoma Kinase (ALK) Fusion Protein
Investigating the Effectiveness of an Investigational Medication in ALK-Positive Lung Cancer
Brief description of study.
This randomized phase III trial studies how well crizotinib works and compares it to placebo 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).
Detailed description of study
The purpose of this study is to evaluate whether adjuvant therapy with crizotinib will result in improved overall survival (OS) over placebo for patients with stage IB >= 4 cm, II and IIIA, ALK-positive non-small cell lung cancer (NSCLC) following surgical resection.
Eligibility of study
You may be eligible for this study if you meet the following criteria:
- Conditions: Anaplastic Lymphoma Kinase,ALK,non-small cell lung cancer,non small cell lung cancer,non-small cell,non small cell,lung cancer,cancer,lung,lungs,oncology
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Age: 18 years - 100 years
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Gender: All
Inclusion Criteria
Patients must have undergone complete surgical resection of their stage IB (>= 4 cm), II, or non-squamous IIIA 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) with or without contrast must be performed within 6 months (180 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
Patients 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)
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; a female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria:
1) has not undergone a hysterectomy or bilateral oophorectomy; or
2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
Women of childbearing potential and sexually active males must be strongly advised to practice abstinence or use an accepted and effective method of contraception
Patients 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
Patients 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
8 months (240 days) if adjuvant chemotherapy was administered
10 months (300 days) if adjuvant chemotherapy and radiation therapy were administered
Patients must have completed any prior adjuvant 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
This study investigates the effectiveness of an investigational medication compared to a placebo in treating patients with stage IB-IIIA non-small cell lung cancer (NSCLC) that has been surgically removed and has a mutation in the anaplastic lymphoma kinase (ALK) gene. ALK is a protein that, when altered, can contribute to the growth of cancer cells. The purpose of this study is to determine if the investigational medication can improve overall survival in patients with ALK-positive NSCLC after surgery.
Participants in the study will be randomly assigned to receive either the investigational medication or a placebo. A placebo is an inactive substance that looks like the investigational medicine but does not contain any medicine. This study will involve regular monitoring and assessments to evaluate the health and progress of the participants.
- Who can participate: Adults who have had complete surgical removal of stage IB (tumor size 4 cm or larger), II, or IIIA non-squamous NSCLC with negative margins are eligible. Participants must have a positive ALK gene mutation and meet specific health criteria, including a good performance status and no uncontrolled illnesses. Participants must also be registered to the ALCHEMIST-SCREEN trial and must not have received prior treatment with crizotinib.
- Study details: Participants must follow the study guidelines and attend all scheduled visits.