Clinical and Genetic Studies of Li-Fraumeni Syndrome
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| ClinicalTrials.gov Identifier: NCT01443468 |
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Recruitment Status :
Recruiting
First Posted : September 29, 2011
Last Update Posted : May 26, 2023
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Background:
- Li-Fraumeni syndrome (LFS) is a genetic condition that increases the risk for some types of cancer. LFS may lead to cancer of the bone or connective tissue, breast, and brain. It may also increase the risk for certain types of leukemia and other cancers. The only known cause of LFS is a change (called a mutation ) in a gene known as TP53. However, not all people with LFS have a TP53 mutation. Researchers want to study other possible genetic causes of LFS, and factors that may increase or decrease cancer risk in people with the syndrome.
Objectives:
- To learn more about the types of cancers that occur in individuals with LFS.
- To study the role of the TP53 gene in the development of cancer.
- To look for other possible genes that cause LFS
- To study the effect of LFS diagnosis on families.
- To determine if environmental factors or other genes can change a person s cancer risk associated with LFS.
Eligibility:
- Individuals with a family or personal medical history of cancers consistent with LFS.
- Individuals with a family or personal medical history of cancers that does not meet the diagnosis of LFS, but the history is suggestive for LFS (meets the diagnosis for the so-called Li-Fraumeni like syndrome)
- Individuals with certain rare cancers
- Individuals with a family or personal history of a TP53 gene mutation, with or without related cancer(s).
Design:
- Participants will fill out a medical history questionnaire and a family history questionnaire.
- Blood samples will be collected for DNA and for storage. Cheek cell samples may be collected if blood cannot be obtained for DNA. Participants can choose to have or not have cancer screening with blood tests, imaging studies, and other exams.
- Participants will complete questionnaires about their worries about cancer, stress levels, and coping strategies. Diet and physical activity questionnaires will also be given. Other psychological tests may be given as needed.
- Participants will be monitored for several years, with regular followup visits to the National Institutes of Health, if indicated. Any changes in health or cancer status will be recorded.
| Condition or disease |
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| Li-Fraumeni Syndrome Neoplasms Tp53 Mutations |
Study Description:
This is a natural history study involving questionnaires, clinical and research evaluations, clinical and research laboratory tests, review of
medical records, and cancer surveillance. This is a prospective long-term study of individuals at high risk of cancer due to Li-Fraumeni Syndrome (LFS) or Li-Fraumeni-Like Syndrome (LFL), using a cohort approach. Enrollees are invited to participate in all aspects of the study but can choose to opt out of specific part(s).
Objectives:
Primary Objectives:
- To ascertain/enroll individuals and families with Li-Fraumeni Syndrome (LFS) and Li-Fraumeni-Like Syndrome (LFL)
- To evaluation and define the clinical spectrum and natural history of disease in LFS and LFL
- To quantify cumulative cancer risk in individuals with LFS or LFL
- To develop a cancer screening program for individuals with LFS or LFL
- To investigate the mechanisms of tumorigenesis in LFS-related tumors (e.g., cell proliferation, growth regulation, apoptosis)
- To identify genetic determinants, environmental factors, and gene-environment interactions that potentially modify cancer risk in
these high-risk individuals
- To evaluate the psychological, behavioral, and social functioning effects of LFS on affected individuals and their family members
- To explore the plausibility of lifestyle interventions as potential strategies for cancer risk reduction
- To create an annotated biospecimen repository of LFS-related for translational, etiologic, and outcomes research
Secondary Objectives:
-To evaluate specific tumor characteristics, including histologies (e.g., leukemia types, brain tumor types, etc.) of cancers
diagnosed in individuals with LFS or LFL.
-To evaluate the potential effect of therapeutic radiation and radiation exposure from diagnostic/screening imaging studies on
cancer risk.
- To provide education, cancer risk assessment, and risk management recommendations for study participants.
- To collect clinical data related to the treatment of LFS-related cancers, so that outcome and survival may be evaluated.
Endpoints: Primary Endpoint:
-Occurrence of cancer in individuals and families with LFS or LFL
| Study Type : | Observational |
| Estimated Enrollment : | 5000 participants |
| Observational Model: | Family-Based |
| Time Perspective: | Prospective |
| Official Title: | Clinical, Epidemiologic, and Genetic Studies of Li-Fraumeni Syndrome |
| Actual Study Start Date : | January 17, 2012 |
| Group/Cohort |
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Patients within a family with a known TP53 mutation who are positive for that mutation.
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Patients within a family with a known TP53 mutation who are negative for that mutation.
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Unaffected family members.
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Patients who meet clinical LFS criteria but haven't had TP53 testing.
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Patients within a family with an negative/unknown TP53 mutation.
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- Prevalence [ Time Frame: ongoing ]Learn more about the types of cancers that occur in individuals with LFS and the age at which these cancers are usually found
- Multiple measures [ Time Frame: ongoing ]Explore ways to lower cancer risk
- Multiple measures [ Time Frame: ongoing ]Explore the typical features of the cancers diagnosed in individuals with LFS
- Multiple measures [ Time Frame: ongoing ]Explore the psychological and social functioning issues faced by LFS families
- Multiple measures [ Time Frame: ongoing ]Explore the best ways to look for cancers early in individuals with LFS
- Multiple measures [ Time Frame: ongoing ]Determine if there is any connection between specific mutations in the TP53 gene and the risk of certain type of cancers
- Multiple measures [ Time Frame: ongoing ]Determine if there are any environmental factors or other genes that can change a person's cancer risk associated with LFS
- Multiple measures [ Time Frame: ongoing ]Determine how often a change (mutation) in the TP53 gene is found in families in which LFS is suspected
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | Child, Adult, Older Adult |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | Yes |
| Sampling Method: | Non-Probability Sample |
- INCLUSION CRITERIA:
- On referral, persons of all ages will be considered for inclusion in the study
because of either:
- A family or personal medical history of neoplasia consistent with the diagnosis of LFS or LFL; or,
- A personal history of a germline TP53 mutation; or,
- A first- or second- degree relative of a TP53 mutation carrier, regardless of mutation status; or,
- A personal history of three or more LFS-related primary cancers; or,
- A personal history of adrenal cortical carcinoma or choroid plexus carcinoma at any age, regardless of family history
Personal and family medical history must be verified through questionnaires, interviews, review
of medical records and/or review of pathology slides.
There are 72 families who have previously enrolled in the pilot study under protocol 78-C-0039.
As the eligibility criteria remain the same, these families will be eligible for this protocol and will be invited to sign the new consent.
-Ability of subject or Legally Authorized Representative (LAR) to understand and the willingness to sign a written informed consent document.
For both the Field and Clinical Center Cohort, the PI will ensure that study investigators will
identify an appropriate LAR consistent with requirements of Policy 403 and will obtain consent
from the LAR as outlined in the consent process before initiating research interventions.
-Pregnant women
In order to study the lifetime rates of cancer development in all individuals with Li-Fraumeni
syndrome, we will need to evaluate what effect pregnancy may have on rate of cancer
development both in affected individuals and unaffected family controls. Additionally, some
cancers are known to have an increased risk of development in the context of pregnancy and
lactation. Exclusion of pregnant women would preclude understanding of these cancer risks for
an important subset of the population.
Pregnant women are eligible for enrollment on the data collection component of this study.
Pregnant women will be included in this study as several endpoints may be assessed during
pregnancy; counseling, education, and other minimal risk procedures (i.e. blood draw) may be
done. We will postpone full clinical evaluations at the Clinical Center of pregnant women until
the subject has recovered post-partum.
All screening studies, for women who are pregnant, or breastfeeding will be deferred while the
woman is pregnant or breastfeeding. Pregnancy testing will be performed for females of childbearing age prior to imaging studies, and the test results must be negative prior to the scan..
The risk to the fetus and pregnant woman would be no greater than minimal for procedures that
are performed.
EXCLUSION CRITERIA:
- Referred individuals and families whose reported diagnoses cannot be verified
- Medical or psychiatric disorder which, in the opinion of the Principal Investigator, would preclude the ability to participate in clinical research
- Women who are pregnant will not be eligible for the cancer screening protocol until they recover post-partum. Women participating in the cancer screening protocol will discontinue this component if they become pregnant while on study. Once they recover post-partum, they can continue the cancer screening protocol.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01443468
| Contact: NCI Family Study Referrals | (800) 518-8474 | ncifamilystudyreferrals@mail.nih.gov | |
| Contact: Payal P Khincha, M.D. | (240) 276-7267 | payal.khincha@nih.gov |
| United States, Maryland | |
| National Cancer Institute - Shady Grove | Recruiting |
| Bethesda, Maryland, United States, 20892 | |
| Contact: Payal Khincha, M.D. 240-276-7267 payal.khincha@nih.gov | |
| National Institutes of Health Clinical Center | Recruiting |
| Bethesda, Maryland, United States, 20892 | |
| Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office 888-624-1937 | |
| Principal Investigator: | Payal P Khincha, M.D. | National Cancer Institute (NCI) |
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT01443468 |
| Other Study ID Numbers: |
110255 11-C-0255 |
| First Posted: | September 29, 2011 Key Record Dates |
| Last Update Posted: | May 26, 2023 |
| Last Verified: | May 19, 2023 |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
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Tp53 Cancer Hereditary Genetic Testing Screening |
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Li-Fraumeni Syndrome Syndrome Disease Pathologic Processes Neoplastic Syndromes, Hereditary |
Neoplasms Genetic Diseases, Inborn DNA Repair-Deficiency Disorders Metabolic Diseases |