Investigating Hereditary Risk In Thoracic Cancers (INHERIT)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 500
- 试验地点
- 2
- 主要终点
- Prevalence of rare pathogenic or likely pathogenic germline variants in familial lung cancers
研究概览
简要总结
The purpose of this research study is to learn more about the inherited risk for developing lung cancer.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Other
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •Individuals who decline to consent
- •Individuals who are unable to give consent or assent and are without a designated healthcare proxy
结局指标
主要结局
Prevalence of rare pathogenic or likely pathogenic germline variants in familial lung cancers
时间窗: 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
Prevalence of rare germline non-EGFR mutations
时间窗: 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
Prevalence of rare germline EGFR mutations
时间窗: 3 years
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
Prevalence of rare pathogenic or likely pathogenic germline variants in lung cancer patients with multiple primary cancers or multi-focal NSCLC
时间窗: 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
次要结局
- Repository of Specimens and Data(3 years)
- Preliminary Assessment of History of Lung Cancers(3 years)
- Estimate of Prevalence of Lung Nodules(3 years)
研究者
Jaclyn LoPiccolo, MD
Principal Investigator
Dana-Farber Cancer Institute