Li-Fraumeni & TP53 (LiFT UP): Understanding and Progress

Li-Fraumeni Syndrome Clinical Trial

— LiFT_UP  

Official title:

Li-Fraumeni & TP53: Understanding and Progress (LiFT UP)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04541654
• Other study ID #: 20-226
• Secondary ID: R01CA242218
• Status: Recruiting
• Start date: September 15, 2020
• Est. completion date: December 31, 2025

Study information

• Verified date: March 2024
• Source: Dana-Farber Cancer Institute
• Contact: Judy E Garber, MD, MPH
• Phone: 617-632-5770
• Email: jegarber[@]partners.org
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1500
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Clonal Hematopoiesis
• Hereditary Cancer Syndrome
• Li-Fraumeni Syndrome
• Mosaicism
• Neoplastic Syndromes, Hereditary
• Syndrome
• TP53 Gene Mutation

Intervention

Genetic:
• Data and Specimen Collection
Provide research team and access to relevant medical records Answer short questionnaires periodically Consider consenting to other optional parts of the research such as: Providing up to 3 tubes (15ml) of blood at or near the time of consent, as approved by treating physician (optional). Provide a saliva sample (optional). Provide eyebrow hairs for analysis of DNA from the bulb (15-20 eyebrow plucks) (optional). Provide permission for obtainment of stored tissue specimens from cancer or pre-cancer surgeries or biopsies from the pathology departments where they have been stored (optional). Consider inviting relatives to join the study (optional).

Locations

Country	Name	City	State
United States	Boston Children's Hospital	Boston	Massachusetts
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Judy E. Garber	Boston	Massachusetts

Sponsors (4)

Lead Sponsor	Collaborator
Dana-Farber Cancer Institute	Baylor College of Medicine, City of Hope Medical Center, National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Repository of specimens and data	Examine accuracy of family history and the extent to which families meet various published Li-Fraumeni family criteria or assess for de-novo mutations using descriptive statistics. Exact binomial confidence limits for percents will be calculated at 95% coverage. Tests of difference between >2 groups for binary variables will use the Fisher exact test.	5 years or Study closure
Secondary	Estimation of Cancer Risks in TP53 mutation carriers	Estimate the frequency in ExAc as a population rate and calculate a standardized risk ratio as the ratio of the prevalence of mutations in a given cancer type compared to that in ExAc. P-values and 95% confidence intervals will be calculated assuming the observed number of mutations follows a Poisson distribution with mean equal to the expected value calculated from the ExAC observed frequency.	5 years or Study closure
Secondary	Modified segregation analysis	For each dataset, the following analyses will be performed using MENDEL: a) the relative risk (RR) across age groups is assumed to be constant; b) the RR is assumed to be a continuous, piece wise linear function of age which was constant before age 40 years and after age 60 years, and linear between ages 40 and 60 years	5 years or Study closure
Secondary	Estimation of risk for the more commonly occurring cancers associated with inherited TP53 mutations	P-values and 95% confidence intervals will be calculated	5 years or Study closure