An observational study in Li-Fraumeni Syndrome, Neoplasms and Tp53 Mutations, sponsored by National Cancer Institute (NCI). Recruiting at 2 sites in United States. Per ClinicalTrials.gov, last updated 2026-09-30.
Sponsored by National Cancer Institute (NCI) · Observational
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:
Eligibility:
Design:
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:
these high-risk individuals
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.
Endpoints: Primary Endpoint:
-Occurrence of cancer in individuals and families with LFS or LFL
Eligibility for the LFS study population: - A family or personal medical history of cancers 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
because of either:
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:
Patients within a family with a known TP53 mutation who are positive for that mutation.
Patients within a family with a known TP53 mutation who are negative for that mutation.
Unaffected family members.
Patients who meet clinical LFS criteria but haven't had TP53 testing.
Patients within a family with an negative/unknown TP53 mutation.
Prevalence
Learn more about the types of cancers that occur in individuals with LFS and the age at which these cancers are usually found
Time frame: ongoing
Multiple measures
Explore ways to lower cancer risk
Time frame: ongoing
Multiple measures
Explore the typical features of the cancers diagnosed in individuals with LFS
Time frame: ongoing
Multiple measures
Explore the psychological and social functioning issues faced by LFS families
Time frame: ongoing
Multiple measures
Explore the best ways to look for cancers early in individuals with LFS
Time frame: ongoing
Multiple measures
Determine if there is any connection between specific mutations in the TP53 gene and the risk of certain type of cancers
Time frame: ongoing
Multiple measures
Determine if there are any environmental factors or other genes that can change a person's cancer risk associated with LFS
Time frame: ongoing
Multiple measures
Determine how often a change (mutation) in the TP53 gene is found in families in which LFS is suspected
Time frame: ongoing
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
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National Cancer Institute (NCI)