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

Protocol # :
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
Disease Sites
Principal Investigator
Sands, Jacob
Site Investigator
Briccetti, Frederick
Constantine, Michael
Costa, Daniel
Dagogo-Jack, Ibiayi
Faggen, Meredith, G.
Gainor, Justin
Manera, Lisa, Marie
Rao, Revati
Site Research Nurses
Andan, Christine
Aspinwall, Sheridan
Becker, Simone
Brule, Maurice, N.
Burke, Millicent
Burke, Millicent
Cronis, Charles, Lewis
Drevers, Dawn
Farquhar, Mary
Finn, Kristen
Fleming, Norah, Michelle
Freeman, Stefani, Danielle
Fuller, Frances
Gentile, Alissa
Ginter, Lindsey
Goodwin, Kelly, E.
Hennessy, Kerry
Hixon, Nicole, R.
Hixon, Nicole, R.
Houghton, Nicole
Janell, Samantha
Kelley, Elaine
Lucca, Joan
Lyons, Hannah, Felton
Maloof, Damiana, M.
McGovern, Lauren
Mcnally, Megan
Milton, Gillian, C.
Morse, Linda, K.
O'Neil, Kelly
Souza, Joseph
Stober, Lisa, L.

Trial Description

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.

Eligibility Requirements

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

- 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

- Patient registered to and the ALK fusion status performed centrally on the

- 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

- 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