Investigating Hereditary Risk In Thoracic Cancers (INHERIT) (INHERIT)
Study Overview
Status
Intervention / Treatment
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 Type
Enrollment (Estimated)
Contacts and Locations
Study Contact
- Name: Jaclyn LoPiccolo, MD, PhD
- Phone Number: 617-632-6036
- Email: Jaclyn_LoPiccolo@dfci.harvard.edu
Study Locations
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Massachusetts
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Boston, Massachusetts, United States, 02115
- Not yet recruiting
- Brigham and Women's Hospital
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Contact:
- Jaclyn LoPiccolo, MD, PhD
- Phone Number: 617-632-6036
- Email: Jaclyn_LoPiccolo@dfci.harvard.edu
-
Principal Investigator:
- Jaclyn LoPiccolo, MD, PhD
-
Boston, Massachusetts, United States, 02115
- Recruiting
- Dana-Farber Cancer Institute
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Contact:
- Jaclyn LoPiccolo, MD, PhD
- Phone Number: 617-632-6036
- Email: Jaclyn_LoPiccolo@dfci.harvard.edu
-
Principal Investigator:
- Jaclyn LoPiccolo, MD, PhD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
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 Plan
How is the study designed?
Design Details
- Observational Models: Cohort
- Time Perspectives: Other
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
|---|---|
|
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.
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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.
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|
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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:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Prevalence of rare germline EGFR mutations
Time Frame: 3 years
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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
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3 years
|
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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
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3 years
|
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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
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3 years
|
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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
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3 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Preliminary Assessment of History of Lung Cancers
Time Frame: 3 years
|
To make a preliminary assessment of the natural history of lung cancers occurring in patients with germline EGFR mutations
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3 years
|
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Estimate of Prevalence of Lung Nodules
Time Frame: 3 years
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To generate an initial estimate of the prevalence of CT-detected lung nodules in individuals with germline EGFR mutations
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3 years
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Repository of Specimens and Data
Time Frame: 3 years
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Prospective registry of patients and families with hereditary or familial lung cancer to collect clinicopathologic information and biologic specimens.
|
3 years
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Jaclyn LoPiccolo, MD, PhD, Dana-Farber Cancer Institute
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Neoplasms by Site
- Neoplasms
- Disease Attributes
- Respiratory Tract Diseases
- Lung Diseases
- Respiratory Tract Neoplasms
- Thoracic Neoplasms
- Disease Susceptibility
- Congenital, Hereditary, and Neonatal Diseases and Abnormalities
- Pathological Conditions, Signs and Symptoms
- Lung Neoplasms
- Genetic Diseases, Inborn
- Genetic Predisposition to Disease
- Investigative Techniques
- Clinical Laboratory Techniques
- Diagnostic Techniques and Procedures
- Diagnosis
- Specimen Handling
Other Study ID Numbers
- 21-568
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
- ICF
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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