Clinical trial NCT03088930: Evaluating Crizotinib in the Neoadjuvant Setting in Patients With Non-small Cell Lung Cancer
Official title: A Phase II Trial to Evaluate Crizotinib in the Neoadjuvant Setting in Patients With Surgically Resectable, ALK, ROS1, or MET-oncogene Positive Non-small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lung Cancer, Nonsmall Cell
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
Collaborators: name: Pfizer
First posted: 2017-03-23
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed description: Participants with stage IA-IIIA, surgically resectable lung adenocarcinoma with an activating alteration in ALK, ROS1 or MET will receive neoadjuvant treatment with crizotinib. This neoadjuvant treatment will last 6 weeks and on the last day of dosing of crizotinib, participants will undergo surgical resection, followed by 5 years of follow-up via chart review.

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)

Primary outcomes:
measure: The Number of Participants With an Objective Tumor Response Rate
timeFrame: 6 weeks
Secondary outcomes:
measure: The Number of Participants With Pathologic Response Rate
timeFrame: 37 months
measure: Number of Participants With an Objective Response Rate
timeFrame: 6 weeks post treatment
measure: The Number of Participants With Disease-free Survival (DFS)
timeFrame: 37 months
measure: Overall Survival (OS) Measured in Months
timeFrame: 37 months
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado Denver
state: Colorado
Study officials:
affiliation: University of Colorado, Denver
name: Tejas Patil, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: