Investigating Hereditary Risk In Thoracic Cancers (INHERIT)

NCT ID: NCT05587439

Last Updated: 2025-07-10

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 500 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2023-01-01
• Study Completion Date: 2027-11-01

Brief Summary

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.

Conditions

Lung Cancer; Genetic Disease; Genetic Predisposition; Hereditary Diseases

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: OTHER

Study Groups

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.

Data and Specimen Collection

Intervention Type: GENETIC

• 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

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.

Data and Specimen Collection

Intervention Type: GENETIC

• 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

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

Data and Specimen Collection

Intervention Type: GENETIC

• 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

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

Intervention Type: GENETIC

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Dana-Farber Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Jaclyn LoPiccolo, MD

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jaclyn LoPiccolo, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Dana-Farber Cancer Institute

Locations

Brigham and Women's Hospital

Boston, Massachusetts, United States

Site Status: NOT_YET_RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Jaclyn LoPiccolo, MD, PhD

Role: CONTACT

Jaclyn_LoPiccolo@dfci.harvard.edu

617-632-6036

Facility Contacts

Jaclyn LoPiccolo, MD, PhD

Role: primary

Jaclyn_LoPiccolo@dfci.harvard.edu

617-632-6036

Jaclyn LoPiccolo, MD, PhD

Role: primary

Jaclyn_LoPiccolo@dfci.harvard.edu

617-632-6036

Other Identifiers

21-568

Identifier Type: -

Identifier Source: org_study_id