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Active, not recruitingNCT02201992Updated Dec 19, 2025

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)

A Phase 3 interventional study of Clinical Observation and Crizotinib in ALK Gene Rearrangement, ALK Gene Translocation and ALK Positive, sponsored by ECOG-ACRIN Cancer Research Group. Active, not recruiting at 1,618 sites in 3 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-12-19.

Sponsored by ECOG-ACRIN Cancer Research Group · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
166
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

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.

Read the detailed description

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.

02

Conditions studied

  • ALK Gene Rearrangement
  • ALK Gene Translocation
  • ALK Positive
  • Stage IB Non-Small Cell Lung Carcinoma AJCC v7
  • Stage II Non-Small Cell Lung Cancer AJCC v7
  • Stage IIA Non-Small Cell Lung Carcinoma AJCC v7
  • Stage IIB Non-Small Cell Lung Carcinoma AJCC v7
  • Stage IIIA Non-Small Cell Lung Cancer AJCC v7
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility 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 locally advanced or metastatic cancer requiring systemic therapy within 5 years from randomization, with the exception of in-situ carcinomas and non-melanoma skin cancer; patients must have no previous primary lung cancer diagnosed concurrently or within the past 2 years
  • Patients may not be receiving any other investigational agents while on study
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
166 participants (actual)

Study arms

  • 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 · Other: Laboratory Biomarker Analysis

  • Active comparator
    Arm B (observation)

    Patients undergo observation.

    Other: Clinical Observation · Other: Laboratory Biomarker Analysis

Interventions

  • OtherClinical Observation

    Undergo observation

  • DrugCrizotinib

    Given PO

    Also known as: MET tyrosine kinase inhibitor PF-02341066, PF-02341066, PF-2341066, Xalkori

  • OtherLaboratory Biomarker Analysis

    Correlative studies

05

What researchers measure

Primary outcomes

  1. 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

Secondary outcomes

  1. 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

  2. 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

06

Study locations

1,618 sites
  • University of Alabama at Birmingham Cancer Center
    Birmingham, Alabama 35233, United States
  • Southern Cancer Center PC-Daphne
    Daphne, Alabama 36526, United States
  • Southern Cancer Center PC-Mobile
    Mobile, Alabama 36607, United States
  • Southern Cancer Center PC-Providence
    Mobile, Alabama 36608, United States
  • Southern Cancer Center PC-Springhill
    Mobile, Alabama 36608, United States
  • Anchorage Associates in Radiation Medicine
    Anchorage, Alaska 98508, United States
  • Anchorage Radiation Therapy Center
    Anchorage, Alaska 99504, United States
  • Alaska Breast Care and Surgery LLC
    Anchorage, Alaska 99508, United States
  • Alaska Oncology and Hematology LLC
    Anchorage, Alaska 99508, United States
  • Alaska Regional Hospital
    Anchorage, Alaska 99508, United States
  • Alaska Women's Cancer Care
    Anchorage, Alaska 99508, United States
  • Anchorage Oncology Centre
    Anchorage, Alaska 99508, United States
  • Katmai Oncology Group
    Anchorage, Alaska 99508, United States
  • Providence Alaska Medical Center
    Anchorage, Alaska 99508, United States
  • Fairbanks Memorial Hospital
    Fairbanks, Alaska 99701, United States
  • Banner MD Anderson Cancer Center
    Gilbert, Arizona 85234, United States
  • Kingman Regional Medical Center
    Kingman, Arizona 86401, United States
  • Cancer Center at Saint Joseph's
    Phoenix, Arizona 85004, United States
  • Banner-University Medical Center Phoenix
    Phoenix, Arizona 85006, United States
  • Mayo Clinic Hospital in Arizona
    Phoenix, Arizona 85054, United States
  • Mayo Clinic in Arizona
    Scottsdale, Arizona 85259, United States
  • Banner Boswell Medical Center
    Sun City, Arizona 85351, United States
  • Banner University Medical Center - Tucson
    Tucson, Arizona 85719, United States
  • University of Arizona Cancer Center-North Campus
    Tucson, Arizona 85719, United States
  • Mercy Hospital Fort Smith
    Fort Smith, Arkansas 72903, United States
  • CHI Saint Vincent Cancer Center Hot Springs
    Hot Springs, Arkansas 71913, United States
  • NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro
    Jonesboro, Arkansas 72401, United States
  • John L McClellan Memorial Veterans Hospital
    Little Rock, Arkansas 72205, United States
  • Kaiser Permanente-Anaheim
    Anaheim, California 92806, United States
  • Kaiser Permanente-Deer Valley Medical Center
    Antioch, California 94531, United States
  • Mission Hope Medical Oncology - Arroyo Grande
    Arroyo Grande, California 93420, United States
  • PCR Oncology
    Arroyo Grande, California 93420, United States
  • Sutter Auburn Faith Hospital
    Auburn, California 95602, United States
  • Sutter Cancer Centers Radiation Oncology Services-Auburn
    Auburn, California 95603, United States
  • AIS Cancer Center at San Joaquin Community Hospital
    Bakersfield, California 93301, United States
  • Kaiser Permanente-Baldwin Park
    Baldwin Park, California 91706, United States
  • Kaiser Permanente-Bellflower
    Bellflower, California 90706, United States
  • Alta Bates Summit Medical Center-Herrick Campus
    Berkeley, California 94704, United States
  • Providence Saint Joseph Medical Center/Disney Family Cancer Center
    Burbank, California 91505, United States
  • Mills-Peninsula Medical Center
    Burlingame, California 94010, United States
  • Sutter Cancer Centers Radiation Oncology Services-Cameron Park
    Cameron Park, California 95682, United States
  • Mercy Cancer Center �� Carmichael
    Carmichael, California 95608, United States
  • Mercy San Juan Medical Center
    Carmichael, California 95608, United States
  • Eden Hospital Medical Center
    Castro Valley, California 94546, United States
  • Community Cancer Institute
    Clovis, California 93611, United States
  • University Oncology Associates
    Clovis, California 93611, United States
  • John Muir Medical Center-Concord Campus
    Concord, California 94520, United States
  • City of Hope Corona
    Corona, California 92879, United States
  • Sutter Davis Hospital
    Davis, California 95616, United States
  • City of Hope Comprehensive Cancer Center
    Duarte, California 91010, United States
  • Epic Care-Dublin
    Dublin, California 94568, United States
  • Kaiser Permanente Dublin
    Dublin, California 94568, United States
  • Mercy Cancer Center - Elk Grove
    Elk Grove, California 95758, United States
  • Bay Area Breast Surgeons Inc
    Emeryville, California 94608, United States
  • Epic Care Partners in Cancer Care
    Emeryville, California 94608, United States
  • Kaiser Permanente-Fontana
    Fontana, California 92335, United States
  • Kaiser Permanente-Fremont
    Fremont, California 94538, United States
  • Palo Alto Medical Foundation-Fremont
    Fremont, California 94538, United States
  • Kaiser Permanente-Fresno
    Fresno, California 93720, United States
  • Saint Jude Medical Center
    Fullerton, California 92835, United States
  • Marin Cancer Care Inc
    Greenbrae, California 94904, United States
  • Marin General Hospital
    Greenbrae, California 94904, United States
  • Kaiser Permanente - Harbor City
    Harbor City, California 90710, United States
  • City of Hope at Irvine Lennar
    Irvine, California 92618, United States
  • Kaiser Permanente-Irvine
    Irvine, California 92618, United States
  • UC San Diego Moores Cancer Center
    La Jolla, California 92093, United States
  • City of Hope Antelope Valley
    Lancaster, California 93534, United States
  • Loma Linda University Medical Center
    Loma Linda, California 92354, United States
  • Tibor Rubin VA Medical Center
    Long Beach, California 90822, United States
  • Kaiser Permanente Los Angeles Medical Center
    Los Angeles, California 90027, United States
  • Los Angeles County-USC Medical Center
    Los Angeles, California 90033, United States
  • USC / Norris Comprehensive Cancer Center
    Los Angeles, California 90033, United States
  • Kaiser Permanente West Los Angeles
    Los Angeles, California 90034, United States
  • Cedars Sinai Medical Center
    Los Angeles, California 90048, United States
  • Contra Costa Regional Medical Center
    Martinez, California 94553-3156, United States
  • Fremont - Rideout Cancer Center
    Marysville, California 95901, United States
  • City of Hope Mission Hills
    Mission Hills, California 91345, United States
  • Memorial Medical Center
    Modesto, California 95355, United States
  • Kaiser Permanente-Modesto
    Modesto, California 95356, United States
  • Palo Alto Medical Foundation-Camino Division
    Mountain View, California 94040, United States
  • Palo Alto Medical Foundation-Gynecologic Oncology
    Mountain View, California 94040, United States
  • Sutter Cancer Research Consortium
    Novato, California 94945, United States
  • Alta Bates Summit Medical Center - Summit Campus
    Oakland, California 94609, United States
  • Bay Area Tumor Institute
    Oakland, California 94609, United States
  • Hematology and Oncology Associates-Oakland
    Oakland, California 94609, United States
  • Kaiser Permanente Oakland-Broadway
    Oakland, California 94611, United States
  • Kaiser Permanente-Oakland
    Oakland, California 94611, United States
  • Kaiser Permanente-Ontario
    Ontario, California 91761, United States
  • Saint Joseph Hospital - Orange
    Orange, California 92868, United States
  • Desert Regional Medical Center
    Palm Springs, California 92262, United States
  • Palo Alto Medical Foundation Health Care
    Palo Alto, California 94301, United States
  • Stanford Cancer Institute Palo Alto
    Palo Alto, California 94304, United States
  • Kaiser Permanente - Panorama City
    Panorama City, California 91402, United States
  • Keck Medical Center of USC Pasadena
    Pasadena, California 91105, United States
  • Kaiser Permanente-Rancho Cordova Cancer Center
    Rancho Cordova, California 95670, United States
  • Eisenhower Medical Center
    Rancho Mirage, California 92270, United States
  • Mercy Regional Cancer Center
    Redding, California 96001, United States
  • Mercy Oncology Center
    Redding, California 96002, United States
  • Kaiser Permanente- Marshall Medical Offices
    Redwood City, California 94063, United States
  • Kaiser Permanente-Redwood City
    Redwood City, California 94063, United States

Showing the first 100 of 1,618 sites across 3 countries.

07

Registry details

Key details

Study ID
NCT02201992
Lead sponsor
ECOG-ACRIN Cancer Research Group
Collaborators
National Cancer Institute (NCI)
Responsible party
Sponsor
First posted
Jul 28, 2014
Start date
Mar 23, 2015
Primary completion
May 1, 2036 (estimated)
Completion
May 1, 2036 (estimated)
Last update
Dec 19, 2025

Study contacts

David Gerber
principal investigator · ECOG-ACRIN Cancer Research Group

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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This study is active, not recruiting, as verified in Dec 2025. You cannot join it, but the record below documents what was studied.

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