Evaluating Crizotinib in the Neoadjuvant Setting in Patients With Non-small Cell Lung Cancer
Condition: Lung Cancer, Nonsmall Cell
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Crizotinib
Intervention description: Crizotinib is an oral receptor tyrosine kinase inhibitor of ALK, Hepatocyte Growth Factor Receptor (HGFR, c-Met), and ROS1 (c-ros). Crizotinib will be given as a neoadjuvant therapy before surgical resection. The recommended dose of crizotinib is 250mg orally. Participants on this trial will receive this dose, unless dose modification is necessary.
Intervention MeSH terms: Crizotinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 3.0
Sex: All
Minimum age: 18 Years
Maximum age: 100 Years
Healthy volunteers: No

Summary:

      This study will evaluate the efficacy of crizotinib as induction therapy in participants with
      surgically resectable ALK rearrangement, ROS1 rearrangement, or MET exon 14 mutation positive
      NSCLC.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Stage IA-IIIA NSCLC by 8th edition AJCC staging (that is deemed to be surgically
             resectable by a board certified thoracic surgeon.

          2. Staging by PET-CT scan and MRI brain showing no evidence of metastatic disease
             (mediastinoscopy is not required unless imaging is indeterminate and is then
             considered standard of care)

          3. Documented evidence of an ALK rearrangement (by FISH, IHC, or 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 CLIA-approved
             laboratory.

          4. Measurable disease defined by RECIST 1.1 criteria.

          5. Life expectancy of at least 24 months.

          6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.

          7. Age ≥ 18 years

          8. Have normal QT interval on ECG evaluation QT corrected Fridericia (QTcF) of ≤ 450 ms
             in males or ≤ 470 ms in females

          9. Adequate organ function:

               -  Absolute neutrophil count (ANC) ≥1500/µL

               -  Platelets ≥75,000/µL

               -  Hemoglobin ≥ 10g/dL

               -  AST /ALT ≤ 2.5 x upper limit of normal (ULN)

               -  Total serum bilirubin ≤ 1.5 x ULN

               -  Serum creatinine ≤ 1.5 x UNL

               -  Serum amylase/lipase ≤ 1.5 x UNL

         10. Negative serum pregnancy test within 7 days of D1 of treatment in women of child
             bearing potential.

         11. 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.

         12. Ability to provide signed informed consent and willing and able to comply with all
             study requirements.

        Exclusion Criteria:

          1. Stage IIIB or IV NSCLC.

          2. History or the presence of pulmonary interstitial disease, or drug-related
             pneumonitis.

          3. Malabsorption syndrome or other GI illness that could affect oral absorption of the
             study drug

          4. Inability to swallow oral medications

          5. 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 SBP> 160 and DBP > 100 on 3
                  separate clinic visits or past history of hypertensive urgency, emergency or
                  encephalopathy

          6. Have active infection requiring antibiotics

          7. Pregnant or lactating female.

          8. Prior treatment with an ALK, ROS1 or MET inhibitor

          9. Any prior anticancer therapy for this diagnosis

         10. 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.

         11. 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 HIV and HCV)