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
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 (resectable). Crizotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving crizotinib before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.
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 as part of standard clinical practice)
- 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 (=< 3.0 x ULN for patients with Gilbert syndrome or if liver function abnormalities are due to underlying malignancy)
- Serum creatinine =< 1.5 x ULN
- Serum amylase =< 1.5 x ULN
- Serum lipase =< 1.5 x ULN
- Negative serum pregnancy test within 14 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 not 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])
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT03088930.
PRIMARY OBJECTIVE:
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 OBJECTIVE:
I. To evaluate secondary measures of clinical efficacy in early stage ALK, ROS1 or MET-mutant NSCLC participants treated with crizotinib induction therapy.
TRANSLATIONAL 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.
II. To monitor plasma samples for evidence of tumor deoxyribonucleic acid (DNA) at diagnosis and at post neoadjuvant treatment on day of resection.
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 PhasePhase II
Trial Typetreatment
Lead OrganizationUCHealth University of Colorado Hospital
Principal InvestigatorTejas Patil
- Primary ID16-2025
- Secondary IDsNCI-2017-00887
- ClinicalTrials.gov IDNCT03088930