Lung CancerINHERITNCT05587439
Investigating Hereditary Risk In Thoracic Cancers (INHERIT)
An observational study of Lung Cancer and Genetic Disease, run by Dana-Farber Cancer Institute at 2 sites in United States.
Trial summary
The purpose of this research study is to learn more about the inherited risk for developing lung cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lung Cancer, Genetic Disease, Genetic Predisposition
- What is being tested?
- Data and Specimen Collection
- How many people
- 500 participants
- Where
- 2 sitesUnited States
- Study dates
- 1 Jan 2023to 1 Nov 2027
- 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: Dana-Farber Cancer Institute (DFCI), DFCI affiliates, satellites, or other sites clinics
Who may be able to join
- Cohort 1: individuals with or with high risk of carrying an EGFR T790M or other EGFR germline variant identified in blood or saliva, including via somatic single or multi-gene panel testing (MGPT). This includes both probands and family members.
- Participants with variants of uncertain significance may be eligible at the PI's discretion
- Cohort 2: individuals with or with high risk of carrying non-EGFR germline variants suggestive of a potential inherited lung cancer risk, identified in blood or saliva, including via somatic single or multi-gene panel testing (MGPT). This includes both probands and family members.
- Participants with variants of uncertain significance may be eligible at the PI's discretion
- Cohort 3: individuals with lung cancer who are not known to carry a pathogenic or likely pathogenic variant, and with one of the following:
- first-degree relative with lung cancer
Show all 14Show fewer
- multi-generational family history of lung cancer
- personal history of multiple primary lung cancers or other neoplasms
- multifocal lung cancer This includes both probands and their families.
- For each cohort, the following applies:
- May include blood relatives of individuals with the aforementioned variants or family history, who may be presumed obligate carriers or healthy controls
- Deceased patients may be included in the study. Pathology specimens and public records, such as death certificates, may be used to confirm information. If medical records and/or pathology specimens are needed, consent will be obtained from the descendant's next-of-kin. Next-of-kin refers to the following hierarchy of relatives: spouse, offspring, parents, and siblings. (Any further use of "next-of-kin" in this protocol refers to this hierarchy).
- Data and specimens from previously consented eligible individuals (under Dana-Farber IRB protocol #12-360) will also be deposited into the study database and specimen banks from other investigators as long as their consents permit sharing of specimens and data. It is estimated that approximately 150 individuals may qualify under these criteria.
- Some of the variants identified initially through germline testing may ultimately be shown to not be germline but rather somatic mosaic (ACE or CHIP). These individuals will remain in the study cohort but will not be asked for ongoing questionnaire or repeat specimen donation
Who cannot join
- Individuals who decline to consent
- Individuals who are unable to give consent or assent and are without a designated healthcare proxy
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites, 2 recruiting
- Not yet recruiting
Brigham and Women's Hospital
Boston, Massachusetts, 02115
Jaclyn LoPiccolo, MD, PhD, 617-632-6036, Jaclyn_LoPiccolo@dfci.harvard.edu
Jaclyn LoPiccolo, MD, PhD
- Recruiting
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
Jaclyn LoPiccolo, MD, PhD, 617-632-6036, Jaclyn_LoPiccolo@dfci.harvard.edu
Jaclyn LoPiccolo, MD, PhD
About this study
The purpose of this research study is to learn more about the inherited risk for developing lung cancer.
Read the detailed description
Lung cancer is largely tobacco related, but the contribution of inherited susceptibility has been less well-studied, particularly among never-smokers. The goal of this study is to learn more about genetic susceptibility to lung cancer by studying individuals and families with known pathogenic germline mutations and/or family histories suggestive for heritable lung cancer, specifically in cases where tobacco exposure is minimal. Patients will be identified through somatic multi-gene panel testing (MGPT) as well as through reported personal and family histories of one or multiple cancers.
The overriding goal of this protocol is to follow patients with known germline mutations and strong family histories of lung cancer to better determine their risk of lung cancer and inform a screening paradigm based on this risk. This will allow us to observe the natural history of this disease and better understand the mechanisms underlying lung tumorigenesis in patients with susceptible germline backgrounds. These patients and their families will be enrolled as individuals with or without lung cancer who meet the following criteria: 1) individuals known to carry or at risk for carrying a germline EGFR mutation (T790M or other), identified through family members or by somatic genotyping at diagnosis, 2) individuals known to carry or at risk for carrying a pathogenic germline mutation in genes other than EGFR and with family history of lung cancer, or 3) individuals with no known germline mutation but with minimal exposure to tobacco and family history of lung cancer, personal history of other primary cancers, or multi-focal lung cancer.
This study is designed to create a data and specimen repository as well as follow patients over time to learn how to better predict lung cancer risk for those with certain genetic changes and family history of lung cancer, and to better understand how and why lung cancer develops in families.
The research study procedures include screening for eligibility, collection of information from participants' medical record, short questionnaires, and collecting blood and/or saliva samples. Procedures may also include use of tissue samples, access to medical records and stored specimens from deceased relatives, and contact information of family members.
It is expected that about 500 people will participant in this study.
- Being tested
- Data and Specimen Collection
- Keywords
- Lung Cancer, Genetic Disease, Genetic Predisposition, Hereditary Diseases
- Medical subject headings
- Lung Neoplasms, Genetic Diseases, Inborn, Genetic Predisposition to Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Data and Specimen CollectionGenetic
- Provide blood and/or saliva sample
- Answer short questionnaires
- Consider consenting to other optional parts of the research such as:
- use stored tissue samples related to prior cancer treatment
- Allow access to deceased relatives' medical records and stored specimens
- Provide blood 1x per year for up to 5 years
- Provide contact information of family members
| Study group | Role | What they receive |
|---|---|---|
| Germline EGFR Mutations | Individuals known to carry or at risk for carrying germline EGFR mutations (e.g., T790M, R776G/H/X, V769M, V834L, V843I, P848L, and others that will be identified). Patients with lung cancer with a somatic EGFR mutation prior to the initiation of treatment or who are found to have a suspected germline EGFR mutation via ctDNA analysis are also eligible. Receives: Genetic: Data and Specimen Collection | |
| Germline Non-EGFR Mutations | Individuals known to carry or at risk for carrying non-EGFR germline mutations (e.g., HER2, BRCA2, MET, YAP1, and others that will be identified). Patients with lung cancer with a somatic variant suggestive of a possible hereditary lung cancer risk are also eligible. Receives: Genetic: Data and Specimen Collection | |
| Family History Or Multiple Primaries Or Multi-Focal Non-Small Cell Lung Cancer NSCLC | Individuals and families with history of lung cancer where no pathogenic germline variant has been identified, but ascertained through history of one or more of the following:
* Multi-generational or first-degree relative with lung cancer
* Personal history of multiple primary lung cancers or other neoplasms
* Multi-focal lung cancer Receives: Genetic: Data and Specimen Collection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Prevalence of rare germline EGFR mutations
To determine the prevalence of rare germline EGFR T790M or other (e.g., EGFR V843I and R776H) mutations in lung cancer patients and in relatives of carriers of germline EGFR mutations
Measured: 3 years
Prevalence of rare germline non-EGFR mutations
To determine the prevalence of rare germline non-EGFR mutations (e.g., HER2, BRCA2, MET, YAP1) in lung cancer patients and in relatives of carriers of germline non-EGFR mutations
Measured: 3 years
Prevalence of rare pathogenic or likely pathogenic germline variants in familial lung cancers
To determine prevalence of rare pathogenic or likely pathogenic germline variants in individuals and families where lung cancer has occurred in multiple generations or across multiple family members of the same generation
Measured: 3 years
Prevalence of rare pathogenic or likely pathogenic germline variants in lung cancer patients with multiple primary cancers or multi-focal NSCLC
To determine prevalence of rare pathogenic or likely pathogenic germline variants in lung cancer patients with multiple primary cancers or multi-focal NSCLC
Measured: 3 years
Secondary outcomes (3)
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: 3 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: 3 years
Repository of Specimens and Data
Prospective registry of patients and families with hereditary or familial lung cancer to collect clinicopathologic information and biologic specimens.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Oct 2022
- Study start1 Jan 2023
- Primary completion1 Nov 2027 (estimated)
- Study completion1 Nov 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Cohort
- Time perspective
- Other
- Enrolment
- 500 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Dana-Farber Cancer Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jaclyn LoPiccolo, MD, Dana-Farber Cancer Institute
- Investigators
- Jaclyn LoPiccolo, MD, PhD, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05587439
- Sponsor's protocol ID
- 21-568
- Acronym
- INHERIT
- Status last verified
- Aug 2026
- First submitted
- 17 Oct 2022
- Last updated
- 26 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
Study at a glance
From the registry record, last updated by the sponsor on 26 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigating Hereditary Risk In Thoracic Cancers (INHERIT)
- ClinicalTrials.gov ID
- NCT05587439
- Acronym / sponsor ID
- INHERIT / 21-568
- Keywords
- Lung Cancer, Genetic Disease, Genetic Predisposition, Hereditary Diseases
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 500 participants (estimated)
- Lead sponsor
- Dana-Farber Cancer InstituteUniversity, hospital or other
- Study start
- 1 Jan 2023 (actual)
- Primary completion
- 1 Nov 2027 (estimated)
- Study completion
- 1 Nov 2027 (estimated)
- First posted
- 20 Oct 2022 (actual)
- 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.
The purpose of this research study is to learn more about the inherited risk for developing lung cancer.
Detailed description
Lung cancer is largely tobacco related, but the contribution of inherited susceptibility has been less well-studied, particularly among never-smokers. The goal of this study is to learn more about genetic susceptibility to lung cancer by studying individuals and families with known pathogenic germline mutations and/or family histories suggestive for heritable lung cancer, specifically in cases where tobacco exposure is minimal. Patients will be identified through somatic multi-gene panel testing (MGPT) as well as through reported personal and family histories of one or multiple cancers.
The overriding goal of this protocol is to follow patients with known germline mutations and strong family histories of lung cancer to better determine their risk of lung cancer and inform a screening paradigm based on this risk. This will allow us to observe the natural history of this disease and better understand the mechanisms underlying lung tumorigenesis in patients with susceptible germline backgrounds. These patients and their families will be enrolled as individuals with or without lung cancer who meet the following criteria: 1) individuals known to carry or at risk for carrying a germline EGFR mutation (T790M or other), identified through family members or by somatic genotyping at diagnosis, 2) individuals known to carry or at risk for carrying a pathogenic germline mutation in genes other than EGFR and with family history of lung cancer, or 3) individuals with no known germline mutation but with minimal exposure to tobacco and family history of lung cancer, personal history of other primary cancers, or multi-focal lung cancer.
This study is designed to create a data and specimen repository as well as follow patients over time to learn how to better predict lung cancer risk for those with certain genetic changes and family history of lung cancer, and to better understand how and why lung cancer develops in families.
The research study procedures include screening for eligibility, collection of information from participants' medical record, short questionnaires, and collecting blood and/or saliva samples. Procedures may also include use of tissue samples, access to medical records and stored specimens from deceased relatives, and contact information of family members.
It is expected that about 500 people will participant in this study.
Study design
- Observational model
- Cohort
- Time perspective
- Other
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Germline EGFR Mutations | – | Genetic: Data and Specimen CollectionIndividuals known to carry or at risk for carrying germline EGFR mutations (e.g., T790M, R776G/H/X, V769M, V834L, V843I, P848L, and others that will be identified). Patients with lung cancer with a somatic EGFR mutation prior to the initiation of treatment or who are found to have a suspected germline EGFR mutation via ctDNA analysis are also eligible. |
| Germline Non-EGFR Mutations | – | Genetic: Data and Specimen CollectionIndividuals known to carry or at risk for carrying non-EGFR germline mutations (e.g., HER2, BRCA2, MET, YAP1, and others that will be identified). Patients with lung cancer with a somatic variant suggestive of a possible hereditary lung cancer risk are also eligible. |
| Family History Or Multiple Primaries Or Multi-Focal Non-Small Cell Lung Cancer NSCLC | – | Genetic: Data and Specimen CollectionIndividuals and families with history of lung cancer where no pathogenic germline variant has been identified, but ascertained through history of one or more of the following: * Multi-generational or first-degree relative with lung cancer * Personal history of multiple primary lung cancers or other neoplasms * Multi-focal lung cancer |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Dana-Farber Cancer Institute (DFCI), DFCI affiliates, satellites, or other sites clinics
Key inclusion criteria (14 listed)
- Cohort 1: individuals with or with high risk of carrying an EGFR T790M or other EGFR germline variant identified in blood or saliva, including via somatic single or multi-gene panel testing (MGPT). This includes both probands and family members.
- Cohort 2: individuals with or with high risk of carrying non-EGFR germline variants suggestive of a potential inherited lung cancer risk, identified in blood or saliva, including via somatic single or multi-gene panel testing (MGPT). This includes both probands and family members.
- Cohort 3: individuals with lung cancer who are not known to carry a pathogenic or likely pathogenic variant, and with one of the following:
- For each cohort, the following applies:
Key exclusion criteria (2 listed)
- Individuals who decline to consent
- Individuals who are unable to give consent or assent and are without a designated healthcare proxy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Data and Specimen Collection* Provide blood and/or saliva sample * Answer short questionnaires * Consider consenting to other optional parts of the research such as: * use stored tissue samples related to prior cancer treatment * Allow access to deceased relatives' medical records and stored specimens * Provide blood 1x per year for up to 5 years * Provide contact information of family members | Genetic | Family History Or Multiple Primaries Or Multi-Focal Non-Small Cell Lung Cancer NSCLC, Germline EGFR Mutations, Germline Non-EGFR Mutations |
Primary outcome
Prevalence of rare germline EGFR mutations
Time frame: 3 years
To determine the prevalence of rare germline EGFR T790M or other (e.g., EGFR V843I and R776H) mutations in lung cancer patients and in relatives of carriers of germline EGFR mutations
Prevalence of rare germline non-EGFR mutations
Time frame: 3 years
To determine the prevalence of rare germline non-EGFR mutations (e.g., HER2, BRCA2, MET, YAP1) in lung cancer patients and in relatives of carriers of germline non-EGFR mutations
Prevalence of rare pathogenic or likely pathogenic germline variants in familial lung cancers
Time frame: 3 years
To determine prevalence of rare pathogenic or likely pathogenic germline variants in individuals and families where lung cancer has occurred in multiple generations or across multiple family members of the same generation
Prevalence of rare pathogenic or likely pathogenic germline variants in lung cancer patients with multiple primary cancers or multi-focal NSCLC
Time frame: 3 years
To determine prevalence of rare pathogenic or likely pathogenic germline variants in lung cancer patients with multiple primary cancers or multi-focal NSCLC
3 secondary outcomes
Preliminary Assessment of History of Lung Cancers
Time frame: 3 years
Estimate of Prevalence of Lung Nodules
Time frame: 3 years
Repository of Specimens and Data
Time frame: 3 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 26 Aug 2026.
- Individual participant dataSharing planned: Yes. The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: [contact information for Sponsor Investigator or designee]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
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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.
Jaclyn LoPiccolo, MD, PhD 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 and Genetic Disease, 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 14 inclusion and 2 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: looking for participants now, as of the sponsor's last update on 26 Aug 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?
Contact Jaclyn LoPiccolo, MD, PhD (617-632-6036, Jaclyn_LoPiccolo@dfci.harvard.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Prevalence of rare germline EGFR mutations (time frame: 3 years). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 26 Aug 2026.