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

Sponsor

European Organisation for Research and Treatment of Cancer - EORTC (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT01838577

Collaborator

(none)

2,000

Enrollment

Location

101.9

Duration (Months)

19.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
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 Design

Study Type:

Observational [Patient Registry]

Anticipated Enrollment :

2000 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

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

Study Start Date :

Sep 1, 2013

Anticipated Primary Completion Date :

Dec 1, 2021

Anticipated Study Completion Date :

Mar 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
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).

Arm

Intervention/Treatment

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).

Outcome Measures

Primary Outcome Measures

For the second objective, the primary endpoint is Overall survival (OS) [5 years from FPI]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Royal Marsden	Sutton		United Kingdom

Sponsors and Collaborators

European Organisation for Research and Treatment of Cancer - EORTC

Investigators

Principal Investigator: Sanjay Popat, MD, Royal Marsden Hospital, Chelsea, London, UK

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

European Organisation for Research and Treatment of Cancer - EORTC

ClinicalTrials.gov Identifier:

NCT01838577

Other Study ID Numbers:

EORTC-08114

First Posted:

Apr 24, 2013

Last Update Posted:

Mar 9, 2021

Last Verified:

Mar 1, 2021

Additional relevant MeSH terms:

Carcinoma, Non-Small-Cell Lung

Study Results

No Results Posted as of Mar 9, 2021