INHERIT EGFR - Studying Germline EGFR Mutations



Status:Active, not recruiting
Conditions:Lung Cancer, Cancer
Therapuetic Areas:Oncology
Healthy:No
Age Range:18 - Any
Updated:4/5/2019
Start Date:December 2012
End Date:April 2020

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INHERIT EGFR - INvestigating HEreditary RIsk From T790M: A Multi-Centered Study to Identify and Characterize Individuals Carrying Germline EGFR Mutations

Lung cancer is a common malignancy that is associated with cigarette smoking but can also
affect individuals who never smoked. It is not well understood whether there are hereditary
risk factors that influence the risk of lung cancer.

It has been recently found that a small number of families have an inherited (passed from
parent to child) change in one of their genes that may contribute to an increased tendency to
develop lung cancers, even in never smokers. In some lung cancer patients this gene, called
"EGFR", contains a DNA change known as an "inherited EGFR mutation". Early data indicate that
these inherited EGFR mutations may be associated with an increased risk of lung cancer.

So far, only a small number of families have been found to carry inherited EGFR mutations.
For this reason the risk of lung cancer associated with inherited EGFR mutations is not well
understood. Understanding the risk may help investigators find ways of detecting lung cancer
sooner or reducing the risk of developing lung cancer.

It was recently discovered that lung cancer patients who are found to carry one rare EGFR
mutation in their cancer cells, called "T790M", have an increased risk of carrying an
inherited EGFR mutation in their normal cells as well. This represents a new strategy for
finding individuals and families carrying inherited EGFR mutations.

This research study is designed to find cancer patients whose tumors have this EGFR mutation,
T790M, to find out if they also have an inherited EGFR mutation. Subjects will not have to
undergo a biopsy to participate in this research study. Investigators will collect a saliva
specimen from patients with a T790M in their cancer to find out if they also have an
inherited EGFR mutation.

Study participants found or known to carry an inherited EGFR mutation will have the option of
offering their close relative the opportunity to also participate in this study. Close
relatives can consider testing to see if they also carry the inherited mutation in their
normal cells. Once investigators have identified individuals and relatives that carry
inherited EGFR mutations in their genes, investigators will then try to understand the risk
of lung cancer and other cancers. Individuals with inherited EGFR mutations will also have
the opportunity to participate in future studies related to cancer and other diseases.

This study is being funded in part by the Conquer Cancer Foundation of ASCO and the Bonnie J.
Addario Lung Cancer Foundation.

If a subject have lung cancer or another cancer carrying a T790M mutation in the EGFR gene,
he/she may be eligible to participate in this research study. To determine eligibility, a
subject will need to perform the following steps: provide informed consent, fill out the
study questionnaire and provide medical records documentation.

The study questionnaire should take about 30 minutes to complete. The questionnaire asks for
information on personal and family cancer and health history. The information provided will
help investigators to determine which parts of the study a subject is eligible for. A few
weeks after submitting the questionnaire, a member of the research study team will contact
the subject by telephone to clarify any questions about the response.

For medical records documentation investigators will request permission to obtain and review
medical records pertaining to any personal history of cancer. Subjects will need to complete
a medical record release form to allow investigators to collect medical records regarding
prior cancers and cancer treatment.

After a subject is determined to be eligible, he/she will have a conversation with a genetic
counselor regarding the potential risks, benefits and limitations of genetic testing. A
genetic counselor is an expert in the field of inherited disorders. They work as members of
the health care team and act as a patient advocate providing education and support to the
patient, family and the medical team. If a subject agrees to proceed, he/she will be provided
a kit (by mail or in person) to provide a saliva sample for genetic testing. This involves
spitting into a special container provided by the study. This sample will be sent to a
clinically-certified testing laboratory to determine presence of an inherited EGFR mutation.

Once the results have been determined, the subject will receive a letter with the phone
number of a genetic counselor to call in order to review results of the genetic testing.
Alternatively, a subject can decide not to receive the results of the genetic testing and can
note that on the letter received and send it back to the study team instead of calling for
the results.

If a mutation is found in the saliva sample, a subject will receive information about how to
undergo confirmatory testing of a blood specimen. This can be done at a local laboratory
using a kit that will be mailed. When the results are available a genetic counselor will call
to discuss them. If the confirmatory blood test confirms an inherited mutation, subjects will
receive instructions on how to invite family members to be tested if appropriate.

Investigators will collect material from a prior tumor biopsy (if available), copies of
imaging scans, and medical records to study. The copies of imaging scans will allow study of
the characteristics of nodules in the lungs. This information will be used to answer
additional questions about cancers carrying EGFR T790M mutations.

It will only take a few months to complete the main part of the study. After that, subjects
will be followed every 6 months for 2 years. If a subject allows a piece of a tumor specimen
or DNA to be stored for future investigational studies, then he/she will remain enrolled in
research for as long as the specimen is stored in the specimen bank.

Inclusion Criteria:

To participate in this study a subject must meet the eligibility of one of the following
cohorts:

Cohort 1 - Cancer patients with T790M in their tumor must both:

- Have a diagnosis of cancer of any type (lung cancer or other)

- Have an EGFR mutation identified. Either EGFR T790M identified on tumor genotyping of
their cancer OR on quantitative plasma genotyping with evidence of high level (>40%
allelic fraction) EGFR T790M OR

- Another EGFR mutation previously reported as germline detected on tumor genotyping of
their cancer

Cohort 2 - Relatives of carriers of germline EGFR mutations are eligible as follows:

- First-degree or second-degree relatives of an individual known to carry a germline
EGFR mutation (either T790M or other novel germline EGFR mutation)

- Third-degree relatives of an individual known to carry a germline EGFR mutation
(either T790M or other novel germline EGFR mutation) if the relative has a personal
history of lung cancer or another malignancy

Cohort 3 - Individuals already known to carry a germline EGFR mutation must:

- Have a known germline EGFR mutation (either T790M or other novel germline EGFR
mutation)

Exclusion Criteria:

- Subjects with lung cancer and an acquired T790M mutation first detected after exposure
to an EGFR tyrosine kinase inhibitor such as erlotinib or gefitinib

- Subjects who are too ill to complete the study questionnaire or provide the necessary
specimen for testing

- Subjects who are unable to give informed consent

- Subjects who are unable to speak or read English or Brazilian Portuguese

- Subjects under the age of 18
We found this trial at
3
sites
450 Brookline Ave
Boston, Massachusetts 2215
617-632-3000
Principal Investigator: Geoffrey Oxnard, MD
Phone: 617-632-6049
Dana-Farber Cancer Institute Since it’s founding in 1947, Dana-Farber has been committed to providing adults...
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Boston, MA
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2220 Pierce Ave
Nashville, Tennessee 37232
615-936-8422
Principal Investigator: Georgia Wiesner, MD
Vanderbilt-Ingram Cancer Center The Vanderbilt-Ingram Cancer Center, located in Nashville, Tenn., brings together the clinical...
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Nashville, TN
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410 W 10th Ave
Columbus, Ohio 43210
(614) 293-8652
The Ohio State University, Wexner Medical Center Located in Columbus, The Ohio State University Wexner...
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Columbus, OH
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