E4512 ALCHEMIST

A Randomized Phase III Trial for Surgically Resected Early Stage Non-Small Cell Lung Cancer: Crizotinib Versus Observation for Patients With Tumors Harboring the Anaplastic Lymphoma Kinase (ALK) Fusion Protein

Objective

Primary Objective:

  • 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:

  • To evaluate and compare disease-free survival (DFS) associated with crizotinib.
  • To evaluate the safety profile of crizotinib when given in the adjuvant therapy setting.
  • To collect tumor tissue and blood specimens for future research.

Study Arms

  • Experimental: Arm A (crizotinib)
  • Active Comparator: Arm B (observation)

Eligibility

  • Patients must have undergone complete surgical resection of their stage IB (>= 4 cm), II, or non-squamous IIIA NSCLC
  • 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)
  • 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

NCT ID

NCT02201992