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The purpose of this research study is to learn more about the inherited risk for developing lung cancer.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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:
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|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Data and Specimen Collection | Genetic |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 3 years |
| Estimate of Prevalence of Lung Nodules |
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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.
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:
Exclusion Criteria:
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Dana-Farber Cancer Institute (DFCI), DFCI affiliates, satellites, or other sites clinics
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Jaclyn LoPiccolo, MD, PhD | Contact | 617-632-6036 | Jaclyn_LoPiccolo@dfci.harvard.edu |
| Name | Affiliation | Role |
|---|---|---|
| Jaclyn LoPiccolo, MD, PhD | Dana-Farber Cancer Institute | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Brigham and Women's Hospital | Not yet recruiting | Boston | Massachusetts | 02115 | United States |
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.
Data can be shared no earlier than 1 year following the date of publication
Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu
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| ID | Term |
|---|---|
| D008175 | Lung Neoplasms |
| D030342 | Genetic Diseases, Inborn |
| D020022 | Genetic Predisposition to Disease |
| ID | Term |
|---|---|
| D012142 | Respiratory Tract Neoplasms |
| D013899 | Thoracic Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| D013048 | Specimen Handling |
| ID | Term |
|---|---|
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D008919 | Investigative Techniques |
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Whole blood, serum, saliva, tissue
|
To generate an initial estimate of the prevalence of CT-detected lung nodules in individuals with germline EGFR mutations
| 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. | 3 years |
| Dana-Farber Cancer Institute | Recruiting | Boston | Massachusetts | 02115 | United States |
|
| D008171 |
| Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D004198 | Disease Susceptibility |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |