Clinical trial NCT04541654: Li-Fraumeni & TP53 (LiFT UP): Understanding and Progress
Official title: Li-Fraumeni & TP53: Understanding and Progress (LiFT UP)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Li-Fraumeni Syndrome
TP53 Gene Mutation
Hereditary Cancer Syndrome
Clonal Hematopoiesis
Mosaicism
Keywords: Li-Fraumeni Syndrome
TP53 Gene Mutation (Variant)
Hereditary Cancer Syndrome
Clonal Hematopoiesis
Mosaicism
Lead sponsor: Dana-Farber Cancer Institute
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: City of Hope Medical Center
name: Baylor College of Medicine
First posted: 2020-09-09
Enrollment: 1500
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: FAMILY_BASED
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adults and children with a TP53 gene variant identified in blood or saliva

Brief summary: The purpose of this research study is to learn more about variants in the TP53 gene both associated with Li-Fraumeni Syndrome (LFS), a hereditary cancer risk condition, and TP53 variants found in the blood for other reasons (e.g. ACE/CHIP and mosaicism).

Detailed description: This research study looks to enroll as many people with LFS or TP53 gene variants as possible in order to:

* Better estimate cancer risks in individuals with TP53 variants or LFS, which is a rare condition.
* Learn the range of cancer risks linked to TP53 variants to help individuals and families to improve our ability to counsel patients and families about cancer risks more accurately.
* Improve opportunities for cancer prevention, early detection, and treatment.
* Learn more about the meaning of TP53 variants in the blood that are not inherited (e.g. ACE/CHIP and mosaicism).

Study procedures will include:

* Collecting information from the participant's medical record and short questionnaires.
* Collecting blood, saliva, eyebrow hair and tumor tissue samples (optional).
* Sharing study information with family members (optional).

It is expected that about 1500 people will take part in this research study. Participants will be in this study until it closes or the participant withdraws consent.

The National Cancer Institute is providing funding for part of this study and is considered a study sponsor. They will require that some of the genetic information be made available to the research community without personal identifying information.

Eligibility criteria: Inclusion Criteria:

* Individuals with a TP53 pathogenic or likely pathogenic variant identified in blood or saliva,
* Individuals with variants of uncertain significance in TP53 may be eligible at the PI's discretion,
* Blood relatives of individuals with a TP53 variant, who may be presumed obligate carriers or healthy controls,
* Individuals who meet Classic or Chompret LFS criteria whether or not they have a TP53 gene variant,
* Individuals may enroll their deceased relatives in the study.
* Individuals with a known TP53 variant that is not LFS, but rather ACE, CHIP, or mosaicism.
* Individuals participating in other LFS studies can still enroll in LiFT UP. Investigators may be collaborators.

Exclusion Criteria:

* Individuals who decline to sign consent
* Individuals who are unable to give consent or assent and are without a designated healthcare proxy

Primary outcomes:
measure: Repository of specimens and data
timeFrame: 5 years or Study closure
Secondary outcomes:
measure: Estimation of Cancer Risks in TP53 mutation carriers
timeFrame: 5 years or Study closure
measure: Modified segregation analysis
timeFrame: 5 years or Study closure
measure: Estimation of risk for the more commonly occurring cancers associated with inherited TP53 mutations
timeFrame: 5 years or Study closure
Other outcomes:
Locations:
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Judy E. Garber
state: Massachusetts
Study officials:
affiliation: Dana-Farber Cancer Institute
name: Judy E Garber, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: de Andrade KC, Lee EE, Tookmanian EM, Kesserwan CA, Manfredi JJ, Hatton JN, Loukissas JK, Zavadil J, Zhou L, Olivier M, Frone MN, Shahzada O, Longabaugh WJR, Kratz CP, Malkin D, Hainaut P, Savage SA. The TP53 Database: transition from the International Agency for Research on Cancer to the US National Cancer Institute. Cell Death Differ. 2022 May;29(5):1071-1073. doi: 10.1038/s41418-022-00976-3. Epub 2022 Mar 29. No abstract available.