NCT01754025: INHERIT

INHERIT EGFR - Studying Germline EGFR Mutations

Active, enrolled Last updated 25 November 2025

What this trial tests

trial in Lung Cancer in 121 participants. Participants enrolled and being followed up; not accepting new ones.

Timeline

28 December 2012

Primary endpoint
7 November 2018

31 December 2029

Quick facts

Lead sponsor	Dana-Farber Cancer Institute
Status	Active, enrolled
Study type	OBSERVATIONAL
Enrollment	121
Start date	28 December 2012
Primary completion	7 November 2018
Estimated completion	31 December 2029
Sites	2 locations across United States

Conditions studied

• Lung Cancer — all drugs for Lung Cancer →

Sponsor

Dana-Farber Cancer Institute

Who can join

18 and older, any sex, with Lung Cancer. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Lung cancer is a common malignancy that is associated with cigarette smoking but can also affect individuals who never smoked. It is not well understood whether there are hereditary risk factors that influence the risk of lung cancer.

It has been recently found that a small number of families have an inherited (passed from parent to child) change in one of their genes that may contribute to an increased tendency to develop lung cancers, even in never smokers. In some lung cancer patients this gene, called "EGFR", contains a DNA change known as an "inherited EGFR mutation". Early data indicate that these inherited EGFR mutations may be associated with an increased risk of lung cancer.

So far, only a small number of families have been found to carry inherited EGFR mutations. For this reason the risk of lung cancer associated with inherited EGFR mutations is not well understood. Understanding the risk may help investigators find ways of detecting lung cancer sooner or reducing the risk of developing lung cancer.

It was recently discovered that lung cancer patients who are found to carry one rare EGFR mutation in their cancer cells, called "T790M", have an increased risk of carrying an inherited EGFR mutation in their normal cells as well. This represents a new strategy for finding individuals and families carrying inherited EGFR mutations.

This research study is designed to find cancer patients whose tumors have this EGFR mutation, T790M, to find out if they also have an inherited EGFR mutation. Subjects will not have to undergo a biopsy to participate in this research study. Investigators will collect a saliva specimen from patients with a T790M in their cancer to find out if they also have an inherited EGFR mutation.

Study participants found or known to carry an inherited EGFR mutation will have the option of offering their close relative the opportunity to also participate in this study. Close relatives can consider testing to see if they also carry the inherited mutation in their normal cells. Once investigators have identified individuals and relatives that carry inherited EGFR mutations in their genes, investigators will then try to understand the risk of lung cancer and other cancers. Individuals with inherited EGFR mutations will also have the opportunity to participate in future studies related to cancer and other diseases.

This study is being funded in part by the Conquer Cancer Foundation of ASCO and the Bonnie J. Addario Lung Cancer Foundation.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Optimizing the sequencing of tyrosine kinase inhibitors (TKIs) in epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC).
   Gelatti ACZ, Drilon A, Santini FC. · · 2019 · cited 172× · PMID 31568888 · DOI 10.1016/j.lungcan.2019.09.017
2. Hereditary lung cancer syndrome targets never smokers with germline EGFR gene T790M mutations.
   Gazdar A, Robinson L, Oliver D, Xing C, et al · · 2014 · cited 114× · PMID 24736066 · DOI 10.1097/jto.0000000000000130
3. Discrimination of Germline <i>EGFR</i> T790M Mutations in Plasma Cell-Free DNA Allows Study of Prevalence Across 31,414 Cancer Patients.
   Hu Y, Alden RS, Odegaard JI, Fairclough SR, et al · · 2017 · cited 66× · PMID 28947568 · DOI 10.1158/1078-0432.ccr-17-1745
4. Germline &lt;i&gt;EGFR&lt;/i&gt; Mutations and Familial Lung Cancer.
   Oxnard GR, Chen R, Pharr JC, Koeller DR, et al · · 2023 · cited 40× · PMID 37579253 · DOI 10.1200/jco.23.01372
5. Clinical Cohort Analysis of Germline &lt;i&gt;EGFR&lt;/i&gt; T790M Demonstrates Penetrance Across Ethnicities and Races, Sexes, and Ages.
   Berry DK, Wang X, Michalski ST, Kang HC, et al · · 2020 · cited 10× · PMID 34164592 · DOI 10.1200/po.19.00297
6. Novel <i>EGFR</i> V834L Germline Mutation Associated With Familial Lung Adenocarcinoma.
   van der Leest C, Wagner A, Pedrosa RM, Aerts JG, et al · · 2018 · cited 9× · PMID 32913987 · DOI 10.1200/po.17.00266
7. Genomic Evolution in a Patient With Lung Adenocarcinoma With a Germline <i>EGFR</i> T790M Mutation.
   Mäkinen N, Zhou M, Bemus M, Nevin J, et al · · 2021 · cited 3× · PMID 34590005 · DOI 10.1016/j.jtocrr.2021.100146
8. Complex Germline K757N Mutation in Non-Small-Cell Lung Cancer: A Case Report.
   Wong B, Moore S, Wheatley-Price P. · · 2022 · PMID 35529290 · DOI 10.1159/000523734