Crizotinib before Surgery in Treating Patients with ALK, ROS1, or MET Mutation Positive Stage IA-IIIA Non-small Cell Lung Cancer That Can Be Removed by Surgery

Status: Active

Description

This phase II trial studies how well giving crizotinib before surgery works in treating patients with ALK, ROS1, or MET mutation positive stage IA-IIIA non-small cell lung cancer that can be removed by surgery. Giving crizotinib before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

Eligibility Criteria

Inclusion Criteria

  • Stage IA-IIIA NSCLC by 8th edition American Joint Committee on Cancer (AJCC) staging (that is deemed to be surgically resectable by a board certified thoracic surgeon
  • Staging by positron emission tomography (PET)-computed tomography (CT) scan (required) and magnetic resonance imaging (MRI) brain (if clinically indicated) showing no evidence of metastatic disease (mediastinoscopy is not required unless imaging is indeterminate and is then considered standard of care)
  • Documented evidence of an ALK rearrangement (by fluorescence in situ hybridization [FISH], immunohistochemistry [IHC], or next generation sequencing [NGS]), ROS1 rearrangement (by FISH or NGS), or MET oncogene as defined by MET exon 14 skipping (NGS), MET Y1003X mutation or MET gene fusion (NGS) in NSCLC tumor specimen by a Clinical Laboratory Improvement Act (CLIA)-approved laboratory
  • Measurable disease defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
  • Life expectancy of at least 24 months
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
  • Have normal QT interval on electrocardiogram (ECG) evaluation QT corrected Fridericia (QTcF) of =< 450 ms in males or =< 470 ms in females
  • Absolute neutrophil count (ANC) >= 1500/uL
  • Platelets >= 75,000/uL
  • Hemoglobin >= 10 g/dL
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN)
  • Total serum bilirubin =< 1.5 x ULN
  • Serum creatinine =< 1.5 x ULN
  • Serum amylase/lipase =< 1.5 x ULN
  • Negative serum pregnancy test within 7 days of day 1 (D1) of treatment in women of child bearing potential
  • If fertile, willing to use highly effective form of contraception (defined as a combination of at least two of the following methods: condom or other barrier methods, oral contraceptives, implantable contraceptives, intrauterine devices) during the dosing period and for at least 4 months after the dosing period
  • Ability to provide signed informed consent and willing and able to comply with all study requirements

Exclusion Criteria

  • Stage IIIB or IV NSCLC as per 8th edition AJCC staging
  • History or the presence of pulmonary interstitial disease, or drug-related pneumonitis
  • Malabsorption syndrome or other gastrointestinal (GI) illness that could affect oral absorption of the study drug
  • Inability to swallow oral medications
  • Have significant, uncontrolled or active cardiovascular disease, specifically including but restricted to: * Myocardial infarction (MI) within 6 months of trial enrollment * Unstable angina within 6 months of trial enrollment * Congestive heart failure (CHF) with 6 months prior to trial enrollment * Any history of ventricular arrhythmia * Cerebrovascular accident or transient ischemic attack within 6 months of D1 of treatment * Clinically significant atrial arrhythmia or severe baseline bradycardia defined as resting heart rate < 50 beat per minute * Uncontrolled hypertension defined as baseline systolic blood pressure (SBP) > 160 and diastolic blood pressure (DBP) > 100 on 3 separate clinic visits or past history of hypertensive urgency, emergency or encephalopathy
  • Have active infection requiring antibiotics
  • Pregnant or lactating female
  • Prior treatment with an ALK, ROS1 or MET inhibitor
  • Any prior anticancer therapy for this diagnosis
  • Any active cancer diagnosis (basal or squamous cell cancers allowed) within the last 5 years for which the patient is receiving active therapy or which is untreated; any cancer diagnosis within the last 5 years that is considered “treated” and/ or on surveillance may be included in the trial
  • Have any condition or illness that, in the opinion of the investigator would compromise patient safety or interfere with evaluation of the study drug (including but not limited to human immunodeficiency virus [HIV] and hepatitis C virus [HCV])

Locations & Contacts

California

San Francisco
UCSF Medical Center-Mount Zion
Status: In review
Contact: Caroline McCoach
Phone: 415-885-3882

Colorado

Aurora
University of Colorado Hospital
Status: Active
Contact: Robert Charles Doebele
Phone: 303-724-2980
Email: Robert.doebele@ucdenver.edu

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To evaluate the efficacy of crizotinib as induction therapy in participants with surgically resectable ALK rearrangement, ROS1 rearrangement, or MET exon 14 mutation positive non-small cell lung cancer (NSCLC).

SECONDARY OBJECTIVES:

I. To evaluate secondary measures of clinical efficacy in early stage ALK, ROS1 or MET-mutant NSCLC participants treated with crizotinib induction therapy.

TERTIARY OBJECTIVES:

I. To evaluate resected tumor samples using genetic, proteomic, and cell imaging techniques to understand mechanisms leading to incomplete tumor response following oncogene-targeted therapy with crizotinib.

OUTLINE:

Patients receive crizotinib orally (PO) twice daily (BID). Treatment continues for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care surgery.

After completion of study treatment, patients are followed every 6 months for 2 years and then annually for 3 years.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
University of Colorado Hospital

Principal Investigator
Robert Charles Doebele

Trial IDs

Primary ID 16-2025
Secondary IDs NCI-2017-00887
Clinicaltrials.gov ID NCT03088930