Crizotinib in Treating Patients With Stage IB-IIIA Non-small Cell Lung Cancer That Has Been Removed by Surgery and ALK Fusion Mutations (An ALCHEMIST Treatment Trial)

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2016 by Eastern Cooperative Oncology Group
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Eastern Cooperative Oncology Group ( ECOG-ACRIN Cancer Research Group )
ClinicalTrials.gov Identifier:
NCT02201992
First received: July 21, 2014
Last updated: March 8, 2016
Last verified: March 2016
  Purpose
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). 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.

Condition Intervention Phase
Stage IB Non-Small Cell Lung Carcinoma
Stage IIA Non-Small Cell Lung Carcinoma
Stage IIB Non-Small Cell Lung Carcinoma
Stage IIIA Non-Small Cell Lung Cancer
Drug: Crizotinib
Other: Laboratory Biomarker Analysis
Other: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Eastern Cooperative Oncology Group:

Primary Outcome Measures:
  • OS [ Time Frame: The time from randomization to death from any cause, assessed up to 10 years ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • DFS [ 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 ] [ Designated as safety issue: No ]
    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.

  • Toxicity rates, determined using the CTCAE version 4.0 [ Time Frame: Up to 10 years ] [ Designated as safety issue: Yes ]
    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.


Estimated Enrollment: 378
Study Start Date: August 2014
Estimated Primary Completion Date: May 2022 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A (crizotinib)
Patients receive crizotinib PO BID on days 1-21. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
Drug: Crizotinib
Given PO
Other Names:
  • MET Tyrosine Kinase Inhibitor PF-02341066
  • PF-02341066
  • PF-2341066
  • Xalkori
Other: Laboratory Biomarker Analysis
Correlative studies
Placebo Comparator: Arm B (placebo)
Patients receive placebo PO BID on days 1-21. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Placebo
Given PO
Other Names:
  • placebo therapy
  • PLCB
  • sham therapy

Detailed Description:

PRIMARY OBJECTIVES:

I. 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.

SECONDARY OBJECTIVES:

I. To evaluate and compare disease-free survival (DFS) associated with crizotinib and placebo.

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 receive placebo PO BID on days 1-21. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically for 10 years.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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) 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; 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

    • 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
    • NOTE: Neo-adjuvant chemotherapy or radiation therapy for the resected lung cancer is not permitted
  • Serum aspartate aminotransferase (AST) and serum alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN)
  • Total serum bilirubin =< 1.5 x ULN
  • Absolute neutrophil count (ANC) >= 1500/mm^3
  • Platelets >= 30,000/mm^3
  • Hemoglobin >= 8.0 g/dL
  • Serum creatinine =< 2 x ULN
  • 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
  • Patients must not have any history of cancer within 5 years from randomization, with the exception of in-situ carcinomas and non-melanoma skin cancer
  • Patients may not be receiving any other investigational agents while on study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02201992

  Show 1039 Study Locations
Sponsors and Collaborators
ECOG-ACRIN Cancer Research Group
National Cancer Institute (NCI)
Investigators
Principal Investigator: David Gerber ECOG-ACRIN Cancer Research Group
  More Information

Responsible Party: ECOG-ACRIN Cancer Research Group
ClinicalTrials.gov Identifier: NCT02201992     History of Changes
Other Study ID Numbers: E4512  NCI-2014-01507  E4512  E4512  U10CA180820  U10CA021115 
Study First Received: July 21, 2014
Last Updated: March 8, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Crizotinib
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 24, 2016