Evaluating Crizotinib in the Neoadjuvant Setting in Patients With Non-small Cell Lung Cancer

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

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.

Study Overview

• Status: Completed
• Conditions: Lung Cancer, Nonsmall Cell
• Intervention / Treatment: Drug: Crizotinib

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.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Neoadjuvant treatment with Crizotinib; Patients enrolled in this study will be treated with 6 weeks of induction therapy with crizotinib. On the last day of dosing, patients will then undergo surgical resection. 5 years of follow-up will be done via chart review.	Drug: Crizotinib; 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.; Other Names: Xalkori

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Number of Participants With an Objective Tumor Response Rate	Participants' tumor response to treatment will be compared from initial/pretreatment scan to 6 week scan using RECIST 1.1	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Number of Participants With Pathologic Response Rate	Pathologic response rate is defined as < 50% of viable tumor present histologically in the resected tumor specimen.	37 months
Number of Participants With an Objective Response Rate	Number of participants with response rate per RECIST 1.1	6 weeks post treatment
The Number of Participants With Disease-free Survival (DFS)	DFS is defined as the time from treatment to the first of either disease recurrence or death from any cause.	37 months
Overall Survival (OS) Measured in Months	OS is defined as the time from study enrollment to death from any cause.	37 months

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Collaborators: Pfizer
• Investigators: Principal Investigator: Tejas Patil, MD, PhD, University of Colorado, Denver

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 13, 2017
• Primary Completion (ACTUAL): January 13, 2021
• Study Completion (ACTUAL): January 13, 2021

Study Registration Dates

• First Submitted: March 17, 2017
• First Submitted That Met QC Criteria: March 17, 2017
• First Posted (ACTUAL): March 23, 2017

Study Record Updates

• Last Update Posted (ACTUAL): February 11, 2022
• Last Update Submitted That Met QC Criteria: January 19, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Crizotinib
• Other Study ID Numbers: 16-2025.cc

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No