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

NCT03088930 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 16-2025.cc
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

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.

Conditions

Lung Cancer, Nonsmall Cell

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• The Number of Participants With Pathologic Response Rate

  37 months

• Number of Participants With an Objective Response Rate

  6 weeks post treatment

• The Number of Participants With Disease-free Survival (DFS)

  37 months

• Overall Survival (OS) Measured in Months

  37 months

Study Arms (1)

Neoadjuvant treatment with Crizotinib

EXPERIMENTAL

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

Interventions

Crizotinib DRUG

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.

Also known as: Xalkori

Neoadjuvant treatment with Crizotinib

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Stage IA-IIIA NSCLC by 8th edition AJCC staging (that is deemed to be surgically resectable by a board certified thoracic surgeon.
• 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)
• 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.
• Measurable disease defined by RECIST 1.1 criteria.
• Life expectancy of at least 24 months.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• Age ≥ 18 years
• Have normal QT interval on ECG evaluation QT corrected Fridericia (QTcF) of ≤ 450 ms in males or ≤ 470 ms in females
• 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

You may not qualify if:

• Stage IIIB or IV NSCLC.
• History or the presence of pulmonary interstitial disease, or drug-related pneumonitis.
• Malabsorption syndrome or other 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 SBP\> 160 and 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

Sponsors & Collaborators

• University of Colorado, Denver: lead
• Pfizer: collaborator

Study Sites (1)

University of Colorado Denver

Aurora, Colorado, 80045, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Crizotinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Aminopyridines; Pyridines

Results Point of Contact

• Title: Dr. Tejas Patil
• Organization: University of Colorado Cancer Center

tajas.patil@cuanschutz.edu

7208489264

Study Officials

• Tejas Patil, MD, PhD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 17, 2017
• First Posted: March 23, 2017
• Study Start: December 13, 2017
• Primary Completion: January 13, 2021
• Study Completion: January 13, 2021
• Last Updated: February 11, 2022
• Results First Posted: February 11, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)