Li-Fraumeni SyndromeLiFT_UPNCT04541654
Li-Fraumeni & TP53 (LiFT UP): Understanding and Progress
An observational study of Li-Fraumeni Syndrome and TP53 Gene Mutation, run by Dana-Farber Cancer Institute at 3 sites in United States.
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). Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Li-Fraumeni Syndrome, TP53 Gene Mutation, Hereditary Cancer Syndrome
- What is being tested?
- Data and Specimen Collection
- How many people
- 1,500 participants
- Where
- 3 sitesUnited States
- Study dates
- 15 Sep 2020to 31 Dec 2032
- How long will I take part?
- 5 Years
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Adults and children with a TP53 gene variant identified in blood or saliva
Who may be able to join
- 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.
Who cannot join
- Individuals who decline to sign consent
- Individuals who are unable to give consent or assent and are without a designated healthcare proxy
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States3 sites, 3 recruiting
- Recruiting
Boston Children's Hospital
Boston, Massachusetts, 02115
JUNNE KAMIHARA, MD, 888-733-4662, jkamihara@partners.org
JUNNE KAMIHARA, MD
- Recruiting
Brigham and Women's Hospital
Boston, Massachusetts, 02215
Judy Garber, MD, MPH, 617-632-2282, jegarber@partners.org
Judy Garber, MD, MPH
- Recruiting
Judy E. Garber
Boston, Massachusetts, 02215
Judy E. Garber, MD, MPH, 617-763-8821, judy_garber@dfci.harvard.edu
Judy Garber, MD, MPH
About this study
Official title: Li-Fraumeni & TP53: Understanding and Progress (LiFT UP)
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).
Read the 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.
- Conditions
- Li-Fraumeni Syndrome, TP53 Gene Mutation, Hereditary Cancer Syndrome, Clonal Hematopoiesis, Mosaicism
- Being tested
- Data and Specimen Collection
- Keywords
- Li-Fraumeni Syndrome, TP53 Gene Mutation (Variant), Hereditary Cancer Syndrome, Clonal Hematopoiesis, Mosaicism
- Medical subject headings
- Li-Fraumeni Syndrome, Neoplastic Syndromes, Hereditary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Data and Specimen CollectionGenetic
- 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).
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Genetic: Data and Specimen Collection |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 5 years or Study closure
Secondary outcomes (3)
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.
Measured: 5 years or Study closure
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
Measured: 5 years or Study closure
Estimation of risk for the more commonly occurring cancers associated with inherited TP53 mutations
P-values and 95% confidence intervals will be calculated
Measured: 5 years or Study closure
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Sep 2020
- Study start15 Sep 2020
- Primary completion31 Dec 2030 (estimated)
- Study completion31 Dec 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Li-Fraumeni SyndromeStudies of the same condition, open and under way.
- More trials run by Dana-Farber Cancer InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Family based
- Time perspective
- Other
- Enrolment
- 1,500 participants (estimated)
- Target duration
- 5 Years
Sponsor and investigators
- Lead sponsor
- Dana-Farber Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI), City of Hope Medical Center, Baylor College of Medicine
- Responsible party
- Principal investigator, Judy E. Garber, MD, Dana-Farber Cancer Institute
- Investigators
- Judy E Garber, MD, MPH, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04541654
- Sponsor's protocol ID
- 20-226
- Other IDs
- R01CA242218
- Acronym
- LiFT_UP
- Status last verified
- Mar 2026
- First submitted
- 25 Aug 2020
- Last updated
- 27 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
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.
PubMed 35352025
Study at a glance
From the registry record, last updated by the sponsor on 27 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Li-Fraumeni & TP53: Understanding and Progress (LiFT UP)
- ClinicalTrials.gov ID
- NCT04541654
- Acronym / sponsor ID
- LiFT_UP / 20-226
- 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
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 1,500 participants (estimated)
- Lead sponsor
- Dana-Farber Cancer InstituteUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI), City of Hope Medical Center, Baylor College of Medicine
- Study start
- 15 Sep 2020 (actual)
- Primary completion
- 31 Dec 2030 (estimated)
- Study completion
- 31 Dec 2032 (estimated)
- First posted
- 9 Sep 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Family based
- Time perspective
- Other
- Target follow-up
- 5 Years
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Variant in the TP53 Gene in blood or saliva | – | Genetic: Data and Specimen CollectionVariant 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 |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Adults and children with a TP53 gene variant identified in blood or saliva
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (2 listed)
- Individuals who decline to sign consent
- Individuals who are unable to give consent or assent and are without a designated healthcare proxy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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). | Genetic | Variant in the TP53 Gene in blood or saliva |
Primary outcome
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.
3 secondary outcomes
Estimation of Cancer Risks in TP53 mutation carriers
Time frame: 5 years or Study closure
Modified segregation analysis
Time frame: 5 years or Study closure
Estimation of risk for the more commonly occurring cancers associated with inherited TP53 mutations
Time frame: 5 years or Study closure
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Mar 2026.
- Derived from this study: PubMed 35352025de 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.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Judy E Garber, MD, MPH principal investigator
Dana-Farber Cancer Institute
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Li-Fraumeni Syndrome and TP53 Gene Mutation, run by Dana-Farber Cancer Institute at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 27 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Judy E Garber, MD, MPH (617-632-5770, jegarber@partners.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Repository of specimens and data (time frame: 5 years or Study closure). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04541654, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Mar 2026.