Purpose

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.

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
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 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

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
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
Active Comparator
Arm B (observation)
Patients undergo observation.
  • Other: Clinical Observation
    Undergo observation
  • Other: Laboratory Biomarker Analysis
    Correlative studies

Recruiting Locations

Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee 37232
Contact:
Site Public Contact
800-811-8480

Vanderbilt Breast Center at One Hundred Oaks
Nashville, Tennessee 37204
Contact:
Site Public Contact
800-811-8480

Vanderbilt-Ingram Cancer Center Cool Springs
Franklin, Tennessee 37067
Contact:
Site Public Contact
800-811-8480

More Details

NCT ID
NCT02201992
Status
Recruiting
Sponsor
ECOG-ACRIN Cancer Research Group

Study Contact

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.