Recruiting

Observational StudyInvestigating Hereditary Risk In Thoracic Cancers (INHERIT)

Sponsor:

Dana-Farber Cancer Institute

Code:

NCT05587439

Conditions

Lung Cancer

Genetic Disease

Genetic Predisposition

Hereditary Diseases

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Data and Specimen Collection

Study Details

Brief summary:

The purpose of this research study is to learn more about the inherited risk for developing lung cancer.

Conditions

Lung Cancer

Genetic Disease

Genetic Predisposition

Hereditary Diseases

Study ID

NCT05587439

Start date

Jan 1, 2023

Status verified date

Aug, 2026

Completion date

Nov 1, 2027

Anticipated

Primary completion date

Nov 1, 2027

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

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
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

Exclusion Criteria:

Individuals who decline to consent
Individuals who are unable to give consent or assent and are without a designated healthcare proxy

Study Design

Enrollment

500 participants

Anticipated

Interventions and Outcome Measures

Arms

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.

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.

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

Interventions

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

Primary outcome measure

Prevalence of rare germline EGFR mutations [ Time Frame: 3 years ]
Prevalence of rare germline non-EGFR mutations [ Time Frame: 3 years ]
Prevalence of rare pathogenic or likely pathogenic germline variants in familial lung cancers [ Time Frame: 3 years ]
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 ]

Central Contacts and Locations

Central contacts

Jaclyn LoPiccolo, MD, PhD

617-632-6036 Jaclyn_LoPiccolo@dfci.harvard.edu

Locations

Dana-Farber Cancer Institute

Recruiting

Boston, Massachusetts, United States, 02115

Contacts

Jaclyn LoPiccolo, MD, PhD

617-632-6036 Jaclyn_LoPiccolo@dfci.harvard.edu

Principal Investigator:

Jaclyn LoPiccolo, MD, PhD

More Information

Sponsor

Dana-Farber Cancer Institute

Last update posted

Aug 26, 2026

Last verified

Aug, 2026

Keywords

Lung Cancer
Genetic Disease
Genetic Predisposition
Hereditary Diseases

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Dana-Farber Cancer Institute on 2026-08-26.