Lung CancerINHERITNCT01754025
INHERIT EGFR - Studying Germline EGFR Mutations
An observational study of Lung Cancer, run by Dana-Farber Cancer Institute at 2 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lung Cancer
- How many people
- 121 participants
- Where
- 2 sitesUnited States
- Study dates
- 28 Dec 2012to 31 Dec 2029
- How long will I take part?
- 2 Years
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Subjects will be identified through participating cancer centers as well as a study website (www.dana-farber.org/T790Mstudy)
Who may be able to join
- To participate in this study a subject must meet the eligibility of one of the following cohorts:
- Cohort 1 - Cancer patients with T790M in their tumor must both:
- Have a diagnosis of cancer of any type (lung cancer or other)
- Have an EGFR mutation identified. Either EGFR T790M identified on tumor genotyping of their cancer OR on quantitative plasma genotyping with evidence of high level (>40% allelic fraction) EGFR T790M OR
- Another EGFR mutation previously reported as germline detected on tumor genotyping of their cancer
- Cohort 2 - Relatives of carriers of germline EGFR mutations are eligible as follows:
Show all 10Show fewer
- First-degree or second-degree relatives of an individual known to carry a germline EGFR mutation (either T790M or other novel germline EGFR mutation)
- Third-degree relatives of an individual known to carry a germline EGFR mutation (either T790M or other novel germline EGFR mutation) if the relative has a personal history of lung cancer or another malignancy
- Cohort 3 - Individuals already known to carry a germline EGFR mutation must:
- Have a known germline EGFR mutation (either T790M or other novel germline EGFR mutation)
Who cannot join
- Subjects with lung cancer and an acquired T790M mutation first detected after exposure to an EGFR tyrosine kinase inhibitor such as erlotinib or gefitinib
- Subjects who are too ill to complete the study questionnaire or provide the necessary specimen for testing
- Subjects who are unable to give informed consent
- Subjects who are unable to speak or read English or Brazilian Portuguese
- Subjects under the age of 18
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, 37232
About this study
Official title: INHERIT EGFR - INvestigating HEreditary RIsk From T790M: A Multi-Centered Study to Identify and Characterize Individuals Carrying Germline EGFR Mutations
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.
Read more
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.
Read the detailed description
If a subject have lung cancer or another cancer carrying a T790M mutation in the EGFR gene, he/she may be eligible to participate in this research study. To determine eligibility, a subject will need to perform the following steps: provide informed consent, fill out the study questionnaire and provide medical records documentation.
The study questionnaire should take about 30 minutes to complete. The questionnaire asks for information on personal and family cancer and health history. The information provided will help investigators to determine which parts of the study a subject is eligible for. A few weeks after submitting the questionnaire, a member of the research study team will contact the subject by telephone to clarify any questions about the response.
For medical records documentation investigators will request permission to obtain and review medical records pertaining to any personal history of cancer. Subjects will need to complete a medical record release form to allow investigators to collect medical records regarding prior cancers and cancer treatment.
After a subject is determined to be eligible, he/she will have a conversation with a genetic counselor regarding the potential risks, benefits and limitations of genetic testing. A genetic counselor is an expert in the field of inherited disorders. They work as members of the health care team and act as a patient advocate providing education and support to the patient, family and the medical team. If a subject agrees to proceed, he/she will be provided a kit (by mail or in person) to provide a saliva sample for genetic testing. This involves spitting into a special container provided by the study. This sample will be sent to a clinically-certified testing laboratory to determine presence of an inherited EGFR mutation.
Once the results have been determined, the subject will receive a letter with the phone number of a genetic counselor to call in order to review results of the genetic testing. Alternatively, a subject can decide not to receive the results of the genetic testing and can note that on the letter received and send it back to the study team instead of calling for the results.
If a mutation is found in the saliva sample, a subject will receive information about how to undergo confirmatory testing of a blood specimen. This can be done at a local laboratory using a kit that will be mailed. When the results are available a genetic counselor will call to discuss them. If the confirmatory blood test confirms an inherited mutation, subjects will receive instructions on how to invite family members to be tested if appropriate.
Investigators will collect material from a prior tumor biopsy (if available), copies of imaging scans, and medical records to study. The copies of imaging scans will allow study of the characteristics of nodules in the lungs. This information will be used to answer additional questions about cancers carrying EGFR T790M mutations.
It will only take a few months to complete the main part of the study. After that, subjects will be followed every 6 months for 2 years. If a subject allows a piece of a tumor specimen or DNA to be stored for future investigational studies, then he/she will remain enrolled in research for as long as the specimen is stored in the specimen bank.
- Conditions
- Lung Cancer
- Keywords
- Gene Mutation
- Medical subject headings
- Lung Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Cancer patients with T790M | Have a diagnosis of cancer of any type. Have an EGFR T790M mutation identified on either genotyping of their cancer at diagnosis OR on quantitative plasma genotyping with evidence of high level (>40% allelic fraction) EGFR T790M. OR another EGFR mutation previously reported as germline detected on tumor genotyping of their cancer. | |
| Relatives of Carriers | Have a relative known to carry a germline EGFR mutation (either T790M or other novel germline EGFR mutation) | |
| Individuals known to be carriers | Have a known germline EGFR mutation (either T790M or other novel germline EGFR mutation) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Prevalence of EGFR mutations
To determine the prevalence of germline EGFR mutations in lung cancer patients with EGFR T790M mutations in their tumor and in relatives of carriers of germline EGFR mutations
Measured: 2 years
Secondary outcomes (5)
Preliminary Assessment of History of Lung Cancers
To make a preliminary assessment of the natural history of lung cancers occurring in patients with germline EGFR mutations
Measured: 2 years
Estimate of Prevalence of Lung Nodules
To generate an initial estimate of the prevalence of CT-detected lung nodules in individuals with germline EGFR mutations
Measured: 2 years
Study EGFR Expression in Skin Biopsies
To study EGFR expression in skin biopsies from patients on study
Measured: 2 years
Explore Relationship Between High Allelic Fraction T790M in plasma genotyping and germline mutations
To explore the relationship between high allelic fraction T790M on plasma genotyping and presence of an underlying germline EGFR T790M mutation
Measured: 2 years
Examine Lung Cancer Risk Associated with Other Germline Mutations
To study individuals and families with rare germline mutations, such as EGFR V843I and EGFR R776H
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Dec 2012 (estimated)
- Study start28 Dec 2012
- Primary completion7 Nov 2018
- Study completion31 Dec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Lung CancerStudies of the same condition, open and under way.
- More trials run by Dana-Farber Cancer InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Family based
- Time perspective
- Prospective
- Enrolment
- 121 participants (actual)
- Target duration
- 2 Years
Sponsor and investigators
- Lead sponsor
- Dana-Farber Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Addario Lung Cancer Medical Institute
- Responsible party
- Principal investigator, Jaclyn LoPiccolo, MD, Dana-Farber Cancer Institute
- Investigators
- Jaclyn LoPiccolo, MD, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01754025
- Sponsor's protocol ID
- 12-360
- Acronym
- INHERIT
- Status last verified
- Nov 2025
- First submitted
- 17 Dec 2012
- Last updated
- 19 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
Publications
Oxnard GR, Miller VA, Robson ME, Azzoli CG, Pao W, Ladanyi M, Arcila ME. Screening for germline EGFR T790M mutations through lung cancer genotyping. J Thorac Oncol. 2012 Jun;7(6):1049-52. doi: 10.1097/JTO.0b013e318250ed9d.
PubMed 22588155Oxnard GR, Chen R, Pharr JC, Koeller DR, Bertram AA, Dahlberg SE, Rainville I, Shane-Carson K, Taylor KA, Sable-Hunt A, Sholl LM, Teerlink CC, Thomas A, Cannon-Albright LA, Fay AP, Ashton-Prolla P, Yang H, Salvatore MM, Addario BJ, Janne PA, Carbone DP, Wiesner GL, Garber JE. Germline EGFR Mutations and Familial Lung Cancer. J Clin Oncol. 2023 Dec 1;41(34):5274-5284. doi: 10.1200/JCO.23.01372. Epub 2023 Oct 23.
PubMed 37579253
Study at a glance
From the registry record, last updated by the sponsor on 19 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- INHERIT EGFR - INvestigating HEreditary RIsk From T790M: A Multi-Centered Study to Identify and Characterize Individuals Carrying Germline EGFR Mutations
- ClinicalTrials.gov ID
- NCT01754025
- Acronym / sponsor ID
- INHERIT / 12-360
- Conditions
- Lung Cancer
- Keywords
- Gene Mutation
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 121 participants (actual)
- Lead sponsor
- Dana-Farber Cancer InstituteUniversity, hospital or other
- Collaborators
- Addario Lung Cancer Medical Institute
- Study start
- 28 Dec 2012 (actual)
- Primary completion
- 7 Nov 2018 (actual)
- Study completion
- 31 Dec 2029 (estimated)
- First posted
- 21 Dec 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
If a subject have lung cancer or another cancer carrying a T790M mutation in the EGFR gene, he/she may be eligible to participate in this research study. To determine eligibility, a subject will need to perform the following steps: provide informed consent, fill out the study questionnaire and provide medical records documentation.
The study questionnaire should take about 30 minutes to complete. The questionnaire asks for information on personal and family cancer and health history. The information provided will help investigators to determine which parts of the study a subject is eligible for. A few weeks after submitting the questionnaire, a member of the research study team will contact the subject by telephone to clarify any questions about the response.
For medical records documentation investigators will request permission to obtain and review medical records pertaining to any personal history of cancer. Subjects will need to complete a medical record release form to allow investigators to collect medical records regarding prior cancers and cancer treatment.
After a subject is determined to be eligible, he/she will have a conversation with a genetic counselor regarding the potential risks, benefits and limitations of genetic testing. A genetic counselor is an expert in the field of inherited disorders. They work as members of the health care team and act as a patient advocate providing education and support to the patient, family and the medical team. If a subject agrees to proceed, he/she will be provided a kit (by mail or in person) to provide a saliva sample for genetic testing. This involves spitting into a special container provided by the study. This sample will be sent to a clinically-certified testing laboratory to determine presence of an inherited EGFR mutation.
Once the results have been determined, the subject will receive a letter with the phone number of a genetic counselor to call in order to review results of the genetic testing. Alternatively, a subject can decide not to receive the results of the genetic testing and can note that on the letter received and send it back to the study team instead of calling for the results.
If a mutation is found in the saliva sample, a subject will receive information about how to undergo confirmatory testing of a blood specimen. This can be done at a local laboratory using a kit that will be mailed. When the results are available a genetic counselor will call to discuss them. If the confirmatory blood test confirms an inherited mutation, subjects will receive instructions on how to invite family members to be tested if appropriate.
Investigators will collect material from a prior tumor biopsy (if available), copies of imaging scans, and medical records to study. The copies of imaging scans will allow study of the characteristics of nodules in the lungs. This information will be used to answer additional questions about cancers carrying EGFR T790M mutations.
It will only take a few months to complete the main part of the study. After that, subjects will be followed every 6 months for 2 years. If a subject allows a piece of a tumor specimen or DNA to be stored for future investigational studies, then he/she will remain enrolled in research for as long as the specimen is stored in the specimen bank.
Study design
- Observational model
- Family based
- Time perspective
- Prospective
- Target follow-up
- 2 Years
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Cancer patients with T790M | – | –Have a diagnosis of cancer of any type. Have an EGFR T790M mutation identified on either genotyping of their cancer at diagnosis OR on quantitative plasma genotyping with evidence of high level (>40% allelic fraction) EGFR T790M. OR another EGFR mutation previously reported as germline detected on tumor genotyping of their cancer. |
| Relatives of Carriers | – | –Have a relative known to carry a germline EGFR mutation (either T790M or other novel germline EGFR mutation) |
| Individuals known to be carriers | – | –Have a known germline EGFR mutation (either T790M or other novel germline EGFR mutation) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Subjects will be identified through participating cancer centers as well as a study website (www.dana-farber.org/T790Mstudy)
Key inclusion criteria (10 listed)
- To participate in this study a subject must meet the eligibility of one of the following cohorts:
- Have a diagnosis of cancer of any type (lung cancer or other)
- Have an EGFR mutation identified. Either EGFR T790M identified on tumor genotyping of their cancer OR on quantitative plasma genotyping with evidence of high level (>40% allelic fraction) EGFR T790M OR
- Another EGFR mutation previously reported as germline detected on tumor genotyping of their cancer
- First-degree or second-degree relatives of an individual known to carry a germline EGFR mutation (either T790M or other novel germline EGFR mutation)
Key exclusion criteria (5 listed)
- Subjects with lung cancer and an acquired T790M mutation first detected after exposure to an EGFR tyrosine kinase inhibitor such as erlotinib or gefitinib
- Subjects who are too ill to complete the study questionnaire or provide the necessary specimen for testing
- Subjects who are unable to give informed consent
- Subjects who are unable to speak or read English or Brazilian Portuguese
- Subjects under the age of 18
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Prevalence of EGFR mutations
Time frame: 2 years
To determine the prevalence of germline EGFR mutations in lung cancer patients with EGFR T790M mutations in their tumor and in relatives of carriers of germline EGFR mutations
5 secondary outcomes
Preliminary Assessment of History of Lung Cancers
Time frame: 2 years
Estimate of Prevalence of Lung Nodules
Time frame: 2 years
Study EGFR Expression in Skin Biopsies
Time frame: 2 years
Explore Relationship Between High Allelic Fraction T790M in plasma genotyping and germline mutations
Time frame: 2 years
Examine Lung Cancer Risk Associated with Other Germline Mutations
Time frame: 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Oct 2026.
- Background: PubMed 22588155Oxnard GR, Miller VA, Robson ME, Azzoli CG, Pao W, Ladanyi M, Arcila ME. Screening for germline EGFR T790M mutations through lung cancer genotyping. J Thorac Oncol. 2012 Jun;7(6):1049-52. doi: 10.1097/JTO.0b013e318250ed9d.
- Derived from this study: PubMed 37579253Oxnard GR, Chen R, Pharr JC, Koeller DR, Bertram AA, Dahlberg SE, Rainville I, Shane-Carson K, Taylor KA, Sable-Hunt A, Sholl LM, Teerlink CC, Thomas A, Cannon-Albright LA, Fay AP, Ashton-Prolla P, Yang H, Salvatore MM, Addario BJ, Janne PA, Carbone DP, Wiesner GL, Garber JE. Germline EGFR Mutations and Familial Lung Cancer. J Clin Oncol. 2023 Dec 1;41(34):5274-5284. doi: 10.1200/JCO.23.01372. Epub 2023 Oct 23.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jaclyn LoPiccolo, MD principal investigator
Dana-Farber Cancer Institute
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Lung Cancer, run by Dana-Farber Cancer Institute at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 19 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Prevalence of EGFR mutations (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01754025, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Oct 2026.