Genetics of EGFR (Epidermal Growth Factor Receptor) Mutation Study (GEM)

Genetics of EGFR Mutation Study (GEM): a Translational Study of the EORTC Lung Group.

The investigators wish to document the distribution of EGFR somatic mutations, and assess the relationship between specific genotype, clinical demographic, therapy, and survival, in a large cohort of EGFR mutant NSCLC.

The investigators also wish to comprehensively investigate the relationship between germline DNA and risk of EGFR mutant NSCLC developing, through a GWAS (Genome-Wide Association Studies) and candidate gene approach, and explore the relationship between germline DNA and clinical outcome, in order to potentially identify germline genetic modifiers of EGFR TKI (Tyrosine Kinase Inhibitor) outcome.

Study Overview

• Status: Active, not recruiting
• Conditions: EGFR Mutation Positive Non Small Cell Lung Cancer

Detailed Description

Objective 1: To identify germline allelic DNA variation associated with somatic EGFR mutation in NSCLC, Objective 2: Correlation between germline allelic variants and survival in EGFR somatic mutant NSCLC.

Objective 3: Study germline allelic DNA variation associated with never /ex light smoking NSCLC.

Objective 4: Catalogue distribution of somatic EGFR mutant genotypes in 1,000 EGFR mutant NSCLC cases and describe their relationship to clinical outcome.

• Study Type: Observational
• Enrollment (Anticipated): 2000

Contacts and Locations

Study Locations

• United Kingdom
  • Sutton, United Kingdom
    • Royal Marsden

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

Case cohort: Patients with proven EGFR mutation in exons 18-21 from tumor material.

Control cohort: Patients known to be somatic EGFR "wild-type," i.e. no mutation detected in exons 18-21 from tumor material.

Description

• Histologically or cytologically diagnosed NSCLC, all histologies are acceptable.
• Patients can be included in the study with any disease stage and at any time during the disease course.
• Any type (surgery, RadioTherapy, chemotherapy, targeted agents) of previous treatment and any line of treatment are eligible.
• Age ≥18 years.

Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol; those conditions should be discussed with the patient before registration in the trial.

Before patient registration, written informed consent must be given according to ICH/GCP (International Conference on Harmonisation/Good Clinical Practice), and national/local regulations.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Case cohort; Patients with proven EGFR mutation in exons 18-21 from tumor material. Patients with unknown or failed tumor EGFR genotyping will be ineligible. Patients subsequently undergoing re-genotyping which demonstrates an EGFR mutation will become eligible for the "case" cohort. No known somatic KRAS, HER2, LKB1, BRAF, or PI3K, mutation or ALK gene rearrangement (or ALK3+ immunohistochemistry). If these mutations are known to be present the patient will be ineligible. However, patients will not be tested specifically for these mutations for this study and patients with unknown status are acceptable. If patients are subsequently tested after enrollment and found to harbor any of these mutations they will be considered ineligible and will be replaced. No known Li Fraumeni, Li Fraumeni-like, or Peutz Jeghers syndrome family, or known germline carriers of mutant LKB1 or TP53. Patients will not have to be tested specifically for these syndromes to be eligible for this study.
Control cohort; Patients known to be somatic EGFR "wild-type," i.e. no mutation detected in exons 18-21 from tumor material. Patients with unknown or failed EGFR genotyping will be ineligible. Patients subsequently undergoing re-genotyping which demonstrates an EGFR wild-type will become eligible for the "control" cohort. Never smoker (<100 cigarettes in lifetime) or ex-light smoker (stopped ≥1 year ago and smoked ≤10 pack-years).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
For the second objective, the primary endpoint is Overall survival (OS)	5 years from FPI

Collaborators and Investigators

• Sponsor: European Organisation for Research and Treatment of Cancer - EORTC
• Investigators: Principal Investigator: Sanjay Popat, MD, Royal Marsden Hospital, Chelsea, London, UK

Study record dates

Study Major Dates

• Study Start: September 1, 2013
• Primary Completion (Anticipated): December 1, 2021
• Study Completion (Anticipated): March 1, 2022

Study Registration Dates

• First Submitted: April 19, 2013
• First Submitted That Met QC Criteria: April 23, 2013
• First Posted (Estimate): April 24, 2013

Study Record Updates

• Last Update Posted (Actual): March 9, 2021
• Last Update Submitted That Met QC Criteria: March 5, 2021
• Last Verified: March 1, 2021

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
• Other Study ID Numbers: EORTC-08114