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

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ClinicalTrials.gov Identifier: NCT03088930
Recruitment Status : Completed
First Posted : March 23, 2017
Last Update Posted : April 23, 2021
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
University of Colorado, Denver

Tracking Information
First Submitted Date  ICMJE March 17, 2017
First Posted Date  ICMJE March 23, 2017
Last Update Posted Date April 23, 2021
Actual Study Start Date  ICMJE December 13, 2017
Actual Primary Completion Date January 13, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 17, 2017)
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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 17, 2017)
  • The number of participants with pathologic response rate [ Time Frame: 5 years follow-up ]
    Pathologic response rate is defined as < 50% of viable tumor present histologically in the resected tumor specimen.
  • The number of participants with metabolic response rate [ Time Frame: 6 weeks post treatment ]
    FDG-PET scan will measure metabolic pre-and post-induction therapy response as per PERCIST criteria
  • The number of participants with disease-free survival (DFS) [ Time Frame: 5 years follow-up ]
    DFS is defined as the time from treatment to the first of either disease recurrence or death from any cause.
  • The number of participants with overall survival (OS) [ Time Frame: 5 years follow-up ]
    OS is defined as the time from study enrollment to death from any cause.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Evaluating Crizotinib in the Neoadjuvant Setting in Patients With Non-small Cell Lung Cancer
Official Title  ICMJE 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
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Lung Cancer, Nonsmall Cell
Intervention  ICMJE 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
Study Arms  ICMJE 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.
Intervention: Drug: Crizotinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 15, 2020)
3
Original Estimated Enrollment  ICMJE
 (submitted: March 17, 2017)
18
Actual Study Completion Date  ICMJE January 13, 2021
Actual Primary Completion Date January 13, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 100 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03088930
Other Study ID Numbers  ICMJE 16-2025.cc
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party University of Colorado, Denver
Study Sponsor  ICMJE University of Colorado, Denver
Collaborators  ICMJE Pfizer
Investigators  ICMJE
Principal Investigator: Tejas Patil, MD, PhD University of Colorado, Denver
PRS Account University of Colorado, Denver
Verification Date April 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP