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

• ClinicalTrials.gov Identifier: NCT03088930
• Recruitment Status: Completed
• First Posted: March 23, 2017
• Results First Posted: February 11, 2022
• Last Update Posted: February 11, 2022
• Sponsor: University of Colorado, Denver
• Collaborator: Pfizer
• Information provided by (Responsible Party): University of Colorado, Denver

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Lung Cancer, Nonsmall Cell	Drug: Crizotinib	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 3 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: December 13, 2017
• Actual Primary Completion Date: January 13, 2021
• Actual Study Completion Date: January 13, 2021

Arms and Interventions

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 Name: Xalkori

Outcome Measures

Primary Outcome Measures :

1. The Number of Participants With an Objective Tumor Response Rate [ Time Frame: 6 weeks ]
   Participants' tumor response to treatment will be compared from initial/pretreatment scan to 6 week scan using RECIST 1.1

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 100 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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)

Contacts and Locations

Locations

United States, Colorado

University of Colorado Denver

Aurora, Colorado, United States, 80045

Sponsors and Collaborators

University of Colorado, Denver

Pfizer

Investigators

• Principal Investigator: Tejas Patil, MD, PhD; University of Colorado, Denver

  Study Documents (Full-Text)

Documents provided by University of Colorado, Denver:

Study Protocol and Statistical Analysis Plan  [PDF] October 20, 2020

Informed Consent Form  [PDF] November 24, 2020

More Information

• Responsible Party: University of Colorado, Denver
• ClinicalTrials.gov Identifier: NCT03088930
• Other Study ID Numbers: 16-2025.cc
• First Posted: March 23, 2017
• Results First Posted: February 11, 2022
• Last Update Posted: February 11, 2022
• Last Verified: January 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Crizotinib; Antineoplastic Agents; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action