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Li-Fraumeni & TP53 (LiFT UP) (LiFT UP)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04541654
Recruitment Status : Recruiting
First Posted : September 9, 2020
Last Update Posted : January 11, 2022
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Judy E. Garber, MD, Dana-Farber Cancer Institute

Study Description
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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).

Condition or disease Intervention/treatment
Li-Fraumeni Syndrome TP53 Gene Mutation Hereditary Cancer Syndrome Clonal Hematopoiesis Mosaicism Genetic: Data and Specimen Collection

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.

Study Design
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Study Type : Observational [Patient Registry]
Estimated Enrollment : 1500 participants
Observational Model: Family-Based
Time Perspective: Other
Target Follow-Up Duration: 5 Years
Official Title: Li-Fraumeni & TP53: Understanding and Progress (LiFT UP)
Actual Study Start Date : September 15, 2020
Estimated Primary Completion Date : December 31, 2025
Estimated Study Completion Date : December 31, 2025

Resource links provided by the National Library of Medicine


Groups and Cohorts
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Group/Cohort Intervention/treatment
Variant in the TP53 Gene in blood or saliva
Variant in the TP53 gene found on a blood or saliva test, have a relative with a variant in the TP53 gene, or because participant meets genetic testing criteria for Li-Fraumeni Syndrome (LFS) based on personal or family cancer history
 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).


Outcome Measures
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Primary Outcome Measures :
  1. Repository of specimens and data [ Time Frame: 5 years or Study closure ]
    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.


Secondary Outcome Measures :
  1. Estimation of Cancer Risks in TP53 mutation carriers [ Time Frame: 5 years or Study closure ]
    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.

  2. Modified segregation analysis [ Time Frame: 5 years or Study closure ]
    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

  3. Estimation of risk for the more commonly occurring cancers associated with inherited TP53 mutations [ Time Frame: 5 years or Study closure ]
    P-values and 95% confidence intervals will be calculated


Biospecimen Retention:   Samples With DNA

Salivary DNA, Hair Follicle Specimens, Tumor or normal Tissue Specimens, Other Specimens*

*Donation by participants of deceased family member's pathology specimen


Eligibility Criteria
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Information from the National Library of Medicine

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.


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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Adults and children with a TP53 gene variant identified in blood or saliva
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
Contacts and Locations
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Information from the National Library of Medicine

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): NCT04541654


Contacts
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Contact: Judy E Garber, MD, MPH 617-632-5770 jegarber@partners.org
Contact: Sophie R Hyman, BS 617-632-4795 SophieR_Hyman@DFCI.HARVARD.edu

Locations
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United States, Massachusetts
Boston Children's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: JUNNE KAMIHARA, MD    888-733-4662    jkamihara@partners.org   
Principal Investigator: JUNNE KAMIHARA, MD         
Brigham and Women's Hospital Recruiting
Boston, Massachusetts, United States, 02215
Contact: Judy Garber, MD, MPH    617-632-2282    jegarber@partners.org   
Principal Investigator: Judy Garber, MD, MPH         
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Judy Garber, MD, MPH    617-632-2282    jegarber@partners.org   
Principal Investigator: Judy Garber, MD, MPH         
Sponsors and Collaborators
Dana-Farber Cancer Institute
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Judy E Garber, MD, MPH Dana-Farber Cancer Institute
More Information
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Responsible Party: Judy E. Garber, MD, Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT04541654    
Other Study ID Numbers: 20-226
R01CA242218 ( U.S. NIH Grant/Contract )
First Posted: September 9, 2020    Key Record Dates
Last Update Posted: January 11, 2022
Last Verified: January 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to Sponsor Investigator or designee]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Time Frame: Data can be shared no earlier than 1 year following the date of publication
Access Criteria: DFCI - Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Judy E. Garber, MD, Dana-Farber Cancer Institute:
Li-Fraumeni Syndrome
TP53 Gene Mutation (Variant)
Hereditary Cancer Syndrome
Clonal Hematopoiesis
Mosaicism
Additional relevant MeSH terms:
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Li-Fraumeni Syndrome
Neoplastic Syndromes, Hereditary
Syndrome
Disease
Pathologic Processes
 Neoplasms
Genetic Diseases, Inborn
DNA Repair-Deficiency Disorders
Metabolic Diseases