Investigating Hereditary Risk In Thoracic Cancers (INHERIT)

NCT05587439 | Recruiting

• 1 other identifier: 21-568
• Study Type: observational
• Target: 500
• Locations: 1 country
• Sites: 2

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

Keywords

Lung Cancer; Genetic Disease; Genetic Predisposition; Hereditary Diseases

Outcome Measures

Primary Outcomes (4)

• 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

  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

  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

  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

  3 years

Secondary Outcomes (3)

• Preliminary Assessment of History of Lung Cancers

  3 years

• Estimate of Prevalence of Lung Nodules

  3 years

• Repository of Specimens and Data

  3 years

Study Arms (3)

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.

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.

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

Genetic: Data and Specimen Collection

Interventions

Data and Specimen Collection 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; Germline EGFR Mutations; Germline Non-EGFR Mutations

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Dana-Farber Cancer Institute (DFCI), DFCI affiliates, satellites, or other sites clinics

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead

Study Sites (2)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

NOT YET RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood, serum, saliva, tissue

MeSH Terms

Conditions

Lung Neoplasms; Genetic Diseases, Inborn; Genetic Predisposition to Disease

Interventions

Specimen Handling

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Disease Susceptibility; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques

Study Officials

• Jaclyn LoPiccolo, MD, PhD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jaclyn LoPiccolo, MD, PhD

CONTACT

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

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 17, 2022
• First Posted: October 20, 2022
• Study Start: January 1, 2023
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): November 1, 2027
• Last Updated: July 10, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (2)