Study of Tumor Samples From Patients With Lung Cancer

A Pilot Project to Study the Expression of c-MET and p53 in Resected Lung Adenocarcinoma Specimens

RATIONALE: Studying samples of tumor tissue from patients with cancer in the laboratory may help doctors learn more about changes that occur in DNA and identify biomarkers related to cancer.

PURPOSE: This laboratory study is looking at tumor samples from patients with lung cancer.

Study Overview

• Status: Completed
• Conditions: Lung Cancer
• Intervention / Treatment: Other: laboratory biomarker analysis

Detailed Description

OBJECTIVES:

Primary

• To determine the correlation between c-Met expression, mutation and amplification, with stage and overall survival in patients with adenocarcinoma (AC) of the lung.

Secondary

• To determine the correlation with epithelial mesenchymal transition (EMT), EGFR mutations and expression, Kras mutations, p53 mutations, c-CBL protein expression, mutation, loss of heterozygosity (LOH), DUB3 expression & regulation, and ALK translocation, with respect to survival.
• To determine the correlation with circulating c-Met and HGF in AC and evaluate prognostic implications of circulating markers in AC of lung.
• To determine (when available) levels of circulating Met and HGF in serum before and after surgery.

OUTLINE: This is a multicenter study.

Previously collected tissue samples from patients enrolled in CALGB 140202 are assessed for mutation analysis of c-Met, EGFR, and K-ras. DNA is examined by PCR, followed by agarose gel electrophoresis; gene amplification of c-Met is examined by real time quantitative PCR; met/HF protein in serum is examined by ELISA; and c-Met, EGFR, p53, c-CBL, DUB3 enzyme, and ALK, and epithelial mesenchymal transition examined by IHC.

• Study Type: Observational
• Enrollment (Actual): 280

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • University of Chicago

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with non-small cell lung adenocarcinoma enrolled on CALCB 140202

Description

Inclusion Criteria:

• Registration to Cancer and Leukemia Group B (CALGB) 140202
• Institutional Review Board (IRB) review and approval at the institution where the laboratory work will be performed is required

• Informed consent: the CALGB does not require that a separate consent form be signed for this study

  • The subject population to be studied in this protocol includes patients selected from CALGB 140202; all such patients have signed a written informed consent document meeting all federal, state, and institutional guidelines as part of entry into that trial
  • All samples to be studied were obtained and stored as part of CALGB 140202; the material and data obtained from the patient's protocol record will be used to obtain appropriate clinical information; in no instance will the patient be contacted directly
  • There should be no physical, psychological, social, or legal risks associated with this study; no invasive procedures are recommended or requested
  • All appropriate and necessary procedures will be utilized to maintain confidentiality; all patients who have had samples submitted for analysis will have their CALGB study number used to identify specimens
  • This study does not require direct patient contact and no specific risk or benefits to individuals involved in the trial are anticipated; it is likely, however, that the information gained will substantially help similar patients in the future

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Ancillary-Correlative (biomarkers in resected AC specimens); Previously collected tissue samples from patients enrolled in CALGB 140202 are assessed for mutation analysis of c-Met, EGFR, Kras, p53, and c-CBL via standard PCR and sequencing; gene amplification of c-Met via real time quantitative PCR; LOH analysis of c-CBL; expression levels of met/HGF protein in serum via ELISA; and expression levels of c-Met, EGFR, p53, c-CBL, DUB3, ALK, and EMT via IHC.

Other: laboratory biomarker analysis; Correlative Studies

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
c-Met expression	The correlation of c-Met expression and stage will be tested using Fisher's exact test. The proportions of c-Met overexpressed in stage I and stage II or higher will be estimated as well as the confidence intervals. The correlation of c-Met expression and survival will be tested using log rank test. The hazard ratio and its confidence interval will be estimated using a Cox model with a single predictor. Summary statistics will be provided for all c-Met measures.	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
EMT expression	The correlation of EMT, EGFR mutations and expression, Kras mutations, p53 mutations, c-CBL protein expression, mutation, and LOH, DUB3 expression, and ALK translocation, circulating c-Met and HGF with respect to survival will be evaluated by Cox model with these markers as continuous predictors or by log rank test with these biomarkers dichotomized at certain cutoff points, such as median or ad hoc optimal cutoff points.	Baseline
Mutations in EGFR, Kras, p53, and c-CBL	The correlation of EMT, EGFR mutations and expression, Kras mutations, p53 mutations, c-CBL protein expression, mutation, and LOH, DUB3 expression, and ALK translocation, circulating c-Met and HGF with respect to survival will be evaluated by Cox model with these markers as continuous predictors or by log rank test with these biomarkers dichotomized at certain cutoff points, such as median or ad hoc optimal cutoff points.	Baseline
c-CBL expression and LOH	The correlation of EMT, EGFR mutations and expression, Kras mutations, p53 mutations, c-CBL protein expression, mutation, and LOH, DUB3 expression, and ALK translocation, circulating c-Met and HGF with respect to survival will be evaluated by Cox model with these markers as continuous predictors or by log rank test with these biomarkers dichotomized at certain cutoff points, such as median or ad hoc optimal cutoff points.	Baseline
DUB3 expression and regulation	The correlation of EMT, EGFR mutations and expression, Kras mutations, p53 mutations, c-CBL protein expression, mutation, and LOH, DUB3 expression, and ALK translocation, circulating c-Met and HGF with respect to survival will be evaluated by Cox model with these markers as continuous predictors or by log rank test with these biomarkers dichotomized at certain cutoff points, such as median or ad hoc optimal cutoff points.	Baseline
ALK Translocation	The correlation of EMT, EGFR mutations and expression, Kras mutations, p53 mutations, c-CBL protein expression, mutation, and LOH, DUB3 expression, and ALK translocation, circulating c-Met and HGF with respect to survival will be evaluated by Cox model with these markers as continuous predictors or by log rank test with these biomarkers dichotomized at certain cutoff points, such as median or ad hoc optimal cutoff points.	Baseline
Circulating c-Met and HGF in AC	The correlation of EMT, EGFR mutations and expression, Kras mutations, p53 mutations, c-CBL protein expression, mutation, and LOH, DUB3 expression, and ALK translocation, circulating c-Met and HGF with respect to survival will be evaluated by Cox model with these markers as continuous predictors or by log rank test with these biomarkers dichotomized at certain cutoff points, such as median or ad hoc optimal cutoff points.	Baseline
Prognostic implications of circulating markers in AC of lung		Baseline
Levels of circulating Met and HGF in serum before and after surgery (when available)		At time of surgery

Collaborators and Investigators

• Sponsor: Alliance for Clinical Trials in Oncology
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Ravi Salgia, MD, PhD, University of Chicago

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (Actual): February 1, 2012
• Study Completion (Actual): September 1, 2012

Study Registration Dates

• First Submitted: May 9, 2009
• First Submitted That Met QC Criteria: May 9, 2009
• First Posted (Estimate): May 12, 2009

Study Record Updates

• Last Update Posted (Actual): August 8, 2017
• Last Update Submitted That Met QC Criteria: August 7, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: recurrent non-small cell lung cancer; stage IIIA non-small cell lung cancer; stage IIIB non-small cell lung cancer; stage IV non-small cell lung cancer; adenocarcinoma of the lung; stage I non-small cell lung cancer; stage II non-small cell lung cancer; stage 0 non-small cell lung cancer
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms
• Other Study ID Numbers: CALGB-150607; U10CA180821 (U.S. NIH Grant/Contract); CDR0000614602 (Registry Identifier: NCI Physician Data Query); NCI-2009-00451 (Registry Identifier: NCI Clinical Trial Reporting Program)