Li-Fraumeni SyndromeNCT04367246
Li-Fraumeni Syndrome/TP53 Biobank
An observational study of Li-Fraumeni Syndrome and Li-Fraumeni-Like Syndrome, run by Abramson Cancer Center at Penn Medicine at 2 sites in United States.
Trial summary
Li-Fraumeni Syndrome (LFS) and Li-Fraumeni-like (LFL) Syndrome are cancer predisposition syndromes due to germline aberrations in the TP53 gene. Patients with classical LFS have a lifetime malignancy risk between 80-90%, with 21% of those cancers occurring by the age of 15 years. Read more about this study
- Who is it for?
- Any ageHealthy volunteers can take part
- Conditions the study is for
- Li-Fraumeni Syndrome, Li-Fraumeni-Like Syndrome
- How many people
- 300 participants
- Where
- 2 sitesUnited States
- Study dates
- 24 Sep 2019to 24 Sep 2029
- 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
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: Patients with LFS/ LFL, family members, and household members
Who may be able to join
- Affected Patient (Group 1)
- Males or females aged 0 and above.
- Confirmed germline TP53 mutation or variant. OR Family history of LFS and clinically managed as a LFS patient. OR Meet LFS diagnostic criteria including Classic, Chompret, and LFL (Birch and Eeles) criteria.
- Informed consent for capable participants. OR Parental/legally authorized representative permission (informed consent) for pediatric participants or subjects with diminished capacity, and if appropriate, assent.
- Unaffected Family Member (Group 2)
- Males or females aged 0 and above.
Show all 13Show fewer
- Biological relative of subjects with germline TP53 mutation or variant (LFS), including first degree (siblings, parents) and second degree (grandparents, aunts, uncles) relatives.
- Negative for germline TP53 mutation or variant.
- Informed consent for capable participants. OR Parental/legally authorized representative permission (informed consent) for pediatric participants or subjects with diminished capacity, and if appropriate, assent.
- Household Member (Group 3)
- Males or females aged 0 and above.
- Household member of subjects with germline TP53 mutation or variant (LFS), sharing a living space (apartment or free-standing home) for at least 6 months prior to study enrollment.
- Informed consent for capable participants. OR Parental/legally authorized representative (LAR) permission (informed consent) for pediatric participants or subjects with diminished capacity, and if appropriate, assent.
Who cannot join
- Parents/LAR or subjects who, in the opinion of the Investigator, may be non-compliant with study schedules or procedures.
- Known pregnancy at the time of study enrollment.
- Subjects that do not meet all of the enrollment criteria may not be enrolled. Pregnant women will not be actively enrolled, but if a woman becomes pregnant she will not be removed from the study; sample collection will be held during known pregnancy.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Miche Duvall contact
United States2 sites, 2 recruiting
- Recruiting
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Kara N Maxwell, MD, PhD, LFS@pennmedicine.upenn.edu
Kara N Maxwell, MD, PhD
- Recruiting
Children's Hospital of Philadelphia
Phildelphia, Pennsylvania, 19104
Suzanne P MacFarland, MD, LFS@chop.edu
Suzanne P MacFarland, MD
About this study
Official title: Clinical and Molecular Studies of Li-Fraumeni Syndrome and TP53-associated Disorders
Li-Fraumeni Syndrome (LFS) and Li-Fraumeni-like (LFL) Syndrome are cancer predisposition syndromes due to germline aberrations in the TP53 gene. Patients with classical LFS have a lifetime malignancy risk between 80-90%, with 21% of those cancers occurring by the age of 15 years. There are established guidelines for screening patients with LFS that have led to earlier detection and treatment of cancer in this population. There are a number of important issues facing patients identified to have germline TP53 variations. First, with the advent of massively parallel sequencing, increasing numbers of patients are now being identified with a wide range of clinical phenotypes associated with germline TP53 mutations, and the natural history of these patients is less well understood. Second, surveillance for malignancy in LFS and other TP53-associated syndromes involves frequent laboratory and radiologic studies that are imperfect measures of disease onset; therefore, more specific, less invasive biomarker-driven screening methods are needed. Finally, studies to date have not yet identified whether tumors which form in LFS or other germline TP53-associated tumors have unique aberrations or signatures that could be exploited in precision medicine treatment of these patients. In order to study these important issues in LFS, this protocol will establish a TP53 Clinical Database and Biobank. The Investigator plans to use this biobank to study genotype-phenotype correlations in patients with LFS and other germline TP53-associated syndromes, mechanisms of tumor formation, and novel methods of cancer screening in this high risk population.
Read the detailed description
Context: Li-Fraumeni Syndrome (LFS) and Li-Fraumeni-like (LFL) Syndrome are cancer predisposition syndromes due to germline aberrations in the TP53 gene. Patients with classical LFS have a lifetime malignancy risk between 80-90%. There are guidelines for screening patients with LFS that have led to earlier detection and treatment of cancer in this population. There are a number of important issues facing patients identified to have germline TP53 variations, including study of genotype-phenotype correlations, enhanced cancer screening modalities, and novel treatment strategies for cancers that develop.
Objectives: In order to study important clinical issues in LFS, the primary objective of this biobank is to gather and store ongoing clinical data and biospecimens from patients with LFS and other potential germline TP53-associated syndromes. The investigators plan to use this biobank to study genotype-phenotype correlations in patients with inherited TP53 mutations, mechanisms of tumor formation, and methods of cancer screening.
Study Design: This study is a retrospective/prospective biobank containing clinical data and data and biospecimen. Patients for inclusion will be identified by query of our clinical electronic medical record from the Children's Hospital of Philadelphia (CHOP) and Penn Medicine (PENN) for patients followed in our respective clinics. In addition, patients will be recruited by ongoing prospective collection in clinic. Data collection, data entry and biobank maintenance, will be conducted by the investigators listed on this protocol at CHOP and at PENN through the Master Reliance Agreement. Future investigators and collaborators at other institutions will have access to samples and limited data by executing a written Data User Agreement and/or Materials Transfer Agreement with the biobank.
Setting/Participants: The biobank will be conducted at CHOP and PENN. Any infant, child, or adult with a germline TP53 mutation will be invited to participate. In addition, individuals with a diagnosis of LFS or LFL, who have been seen by a physician at Penn/CHOP or referred from outside physicians will be contacted for participation. To provide control group samples, unaffected family members and/or household members will also be recruited. Prospective enrollment into the biobank is planned to be an ongoing effort, without a fixed end date or target subject number. At minimum, however, the estimated number of recruitment is approximately 300 affected individuals and their family/household members along with their data and specimens.
Data/Specimen Collection Procedures and Frequency: The only required study procedure is the review of medical records. Optional study procedures include collection of germline DNA (via blood, saliva, urine, or hair), plasma collection, stool collection, and skin biopsies. Clinical data will be updated every 6 months. Subjects can opt-out of this follow-up process.
- Conditions
- Li-Fraumeni Syndrome, Li-Fraumeni-Like Syndrome
- Being tested
- No Intervention
- Keywords
- TP53, TP53 Mutation
- Medical subject headings
- Li-Fraumeni Syndrome, Li-Fraumeni-Like Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
No InterventionOther
No intervention is assigned.
| Study group | Role | What they receive |
|---|---|---|
| Affected Patients | Eligible subjects have a confirmed germline TP53 mutation or variant, OR have a family history of LFS and clinically managed as a LFS patient, OR meet LFS diagnostic criteria including Classic, Chompret, and LFL (Birch and Eeles) criteria. Medical information contribution is required for participation in the study. Subjects also have options to contribute a one-time DNA sample, a blood sample for plasma and a stool sample every six months, as well as access to their residual clinical tissues. Receives: Other: No Intervention | |
| Family Members | Biological relative of subjects with germline TP53 mutation or variant (LFS), including first degree (siblings, parents) and second degree (grandparents, aunts, uncles) relatives. Negative for germline TP53 mutation or variant. Medical information contribution is required for participation in the study. Subjects also have options to contribute a one-time DNA sample, a stool sample, as well as access to their residual clinical tissues. Receives: Other: No Intervention | |
| Household Members | Household member of subjects with germline TP53 mutation or variant (LFS), sharing a living space (apartment or free-standing home) for at least 6 months prior to study enrollment. Medical information contribution is required for participation in the study. Subjects also have options to contribute a one-time stool sample. Receives: Other: No Intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
Descriptive clinical data of all patients with confirmed germline TP53 variants
These data include but are not limited to family history, cancer history, genetic testing, and cancer treatment.
Measured: Five years
Genomic landscape of TP53-associated tumors
Measured: Five years
Sequencing data from prospective blood collection and detection of ctDNA in plasma
Measured: Five years
Secondary outcomes (2)
Utility of ctDNA assay in detection of cancer development in LFS patients
Measured: Five years
Genotype-phenotype correlations in patients with inherited TP53 mutations
Measured: Five years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Apr 2020
- Study start24 Sep 2019
- Primary completion24 Sep 2029 (estimated)
- Study completion24 Sep 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Li-Fraumeni SyndromeStudies of the same condition, open and under way.
- More trials run by Abramson Cancer Center at Penn MedicineThe 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 300 participants (estimated)
- Target duration
- 5 Years
Sponsor and investigators
- Lead sponsor
- Abramson Cancer Center at Penn Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Children's Hospital of Philadelphia
- Responsible party
- Principal investigator, Kara Maxwell, Abramson Cancer Center at Penn Medicine
- Investigators
- Kara N Maxwell, MD, PhD, Principal investigator, University of PennsylvaniaSuzanne MacFarland, MD, Principal investigator, Children's Hospital of Philadelphia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04367246
- Sponsor's protocol ID
- UPCC 24919
- Other IDs
- IRB 18-015810, IRB 834147
- Status last verified
- Sep 2026
- First submitted
- 27 Apr 2020
- Last updated
- 4 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Only a limited data set will be available to future users of the biobank. To access data and biospecimens within the biobank, the prospective recipient executes a written Data User Agreement with the biobank, which will prohibit any attempts to re-identify subjects. Limited data will then be transmitted to prospective researchers using downloaded Excel compatible file formats. PHI will be maintained within the database as part of the consent process, in a partitioned and protected fashion (not available to future investigators) to permit the addition of updated clinical information into the biobank on a periodic basis. If for any reason the study is terminated, all data will be retained for six years, per CHOP policy A-3-9 for data retention. Following the end of data retention, data will be permanently de-coded and de-identified.
Study at a glance
From the registry record, last updated by the sponsor on 4 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical and Molecular Studies of Li-Fraumeni Syndrome and TP53-associated Disorders
- ClinicalTrials.gov ID
- NCT04367246
- Acronym / sponsor ID
- UPCC 24919
- Conditions
- Li-Fraumeni Syndrome, Li-Fraumeni-Like Syndrome
- Keywords
- TP53, TP53 Mutation
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- Abramson Cancer Center at Penn MedicineUniversity, hospital or other
- Collaborators
- Children's Hospital of Philadelphia
- Study start
- 24 Sep 2019 (actual)
- Primary completion
- 24 Sep 2029 (estimated)
- Study completion
- 24 Sep 2029 (estimated)
- First posted
- 29 Apr 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.
Li-Fraumeni Syndrome (LFS) and Li-Fraumeni-like (LFL) Syndrome are cancer predisposition syndromes due to germline aberrations in the TP53 gene. Patients with classical LFS have a lifetime malignancy risk between 80-90%, with 21% of those cancers occurring by the age of 15 years. There are established guidelines for screening patients with LFS that have led to earlier detection and treatment of cancer in this population. There are a number of important issues facing patients identified to have germline TP53 variations. First, with the advent of massively parallel sequencing, increasing numbers of patients are now being identified with a wide range of clinical phenotypes associated with germline TP53 mutations, and the natural history of these patients is less well understood. Second, surveillance for malignancy in LFS and other TP53-associated syndromes involves frequent laboratory and radiologic studies that are imperfect measures of disease onset; therefore, more specific, less invasive biomarker-driven screening methods are needed. Finally, studies to date have not yet identified whether tumors which form in LFS or other germline TP53-associated tumors have unique aberrations or signatures that could be exploited in precision medicine treatment of these patients. In order to study these important issues in LFS, this protocol will establish a TP53 Clinical Database and Biobank. The Investigator plans to use this biobank to study genotype-phenotype correlations in patients with LFS and other germline TP53-associated syndromes, mechanisms of tumor formation, and novel methods of cancer screening in this high risk population.
Detailed description
Context: Li-Fraumeni Syndrome (LFS) and Li-Fraumeni-like (LFL) Syndrome are cancer predisposition syndromes due to germline aberrations in the TP53 gene. Patients with classical LFS have a lifetime malignancy risk between 80-90%. There are guidelines for screening patients with LFS that have led to earlier detection and treatment of cancer in this population. There are a number of important issues facing patients identified to have germline TP53 variations, including study of genotype-phenotype correlations, enhanced cancer screening modalities, and novel treatment strategies for cancers that develop.
Objectives: In order to study important clinical issues in LFS, the primary objective of this biobank is to gather and store ongoing clinical data and biospecimens from patients with LFS and other potential germline TP53-associated syndromes. The investigators plan to use this biobank to study genotype-phenotype correlations in patients with inherited TP53 mutations, mechanisms of tumor formation, and methods of cancer screening.
Study Design: This study is a retrospective/prospective biobank containing clinical data and data and biospecimen. Patients for inclusion will be identified by query of our clinical electronic medical record from the Children's Hospital of Philadelphia (CHOP) and Penn Medicine (PENN) for patients followed in our respective clinics. In addition, patients will be recruited by ongoing prospective collection in clinic. Data collection, data entry and biobank maintenance, will be conducted by the investigators listed on this protocol at CHOP and at PENN through the Master Reliance Agreement. Future investigators and collaborators at other institutions will have access to samples and limited data by executing a written Data User Agreement and/or Materials Transfer Agreement with the biobank.
Setting/Participants: The biobank will be conducted at CHOP and PENN. Any infant, child, or adult with a germline TP53 mutation will be invited to participate. In addition, individuals with a diagnosis of LFS or LFL, who have been seen by a physician at Penn/CHOP or referred from outside physicians will be contacted for participation. To provide control group samples, unaffected family members and/or household members will also be recruited. Prospective enrollment into the biobank is planned to be an ongoing effort, without a fixed end date or target subject number. At minimum, however, the estimated number of recruitment is approximately 300 affected individuals and their family/household members along with their data and specimens.
Data/Specimen Collection Procedures and Frequency: The only required study procedure is the review of medical records. Optional study procedures include collection of germline DNA (via blood, saliva, urine, or hair), plasma collection, stool collection, and skin biopsies. Clinical data will be updated every 6 months. Subjects can opt-out of this follow-up process.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 5 Years
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Affected Patients | – | Other: No InterventionEligible subjects have a confirmed germline TP53 mutation or variant, OR have a family history of LFS and clinically managed as a LFS patient, OR meet LFS diagnostic criteria including Classic, Chompret, and LFL (Birch and Eeles) criteria. Medical information contribution is required for participation in the study. Subjects also have options to contribute a one-time DNA sample, a blood sample for plasma and a stool sample every six months, as well as access to their residual clinical tissues. |
| Family Members | – | Other: No InterventionBiological relative of subjects with germline TP53 mutation or variant (LFS), including first degree (siblings, parents) and second degree (grandparents, aunts, uncles) relatives. Negative for germline TP53 mutation or variant. Medical information contribution is required for participation in the study. Subjects also have options to contribute a one-time DNA sample, a stool sample, as well as access to their residual clinical tissues. |
| Household Members | – | Other: No InterventionHousehold member of subjects with germline TP53 mutation or variant (LFS), sharing a living space (apartment or free-standing home) for at least 6 months prior to study enrollment. Medical information contribution is required for participation in the study. Subjects also have options to contribute a one-time stool sample. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Patients with LFS/ LFL, family members, and household members
Key inclusion criteria (13 listed)
- Affected Patient (Group 1)
- Males or females aged 0 and above.
- Confirmed germline TP53 mutation or variant. OR Family history of LFS and clinically managed as a LFS patient. OR Meet LFS diagnostic criteria including Classic, Chompret, and LFL (Birch and Eeles) criteria.
- Informed consent for capable participants. OR Parental/legally authorized representative permission (informed consent) for pediatric participants or subjects with diminished capacity, and if appropriate, assent.
- Unaffected Family Member (Group 2)
Key exclusion criteria (3 listed)
- Parents/LAR or subjects who, in the opinion of the Investigator, may be non-compliant with study schedules or procedures.
- Known pregnancy at the time of study enrollment.
- Subjects that do not meet all of the enrollment criteria may not be enrolled. Pregnant women will not be actively enrolled, but if a woman becomes pregnant she will not be removed from the study; sample collection will be held during known pregnancy.
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 |
|---|---|---|
| No InterventionNo intervention is assigned. | Other | Affected Patients, Family Members, Household Members |
Primary outcome
Descriptive clinical data of all patients with confirmed germline TP53 variants
Time frame: Five years
These data include but are not limited to family history, cancer history, genetic testing, and cancer treatment.
Genomic landscape of TP53-associated tumors
Time frame: Five years
Sequencing data from prospective blood collection and detection of ctDNA in plasma
Time frame: Five years
2 secondary outcomes
Utility of ctDNA assay in detection of cancer development in LFS patients
Time frame: Five years
Genotype-phenotype correlations in patients with inherited TP53 mutations
Time frame: Five years
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 4 Sep 2026.
- Individual participant dataSharing planned: Undecided. Only a limited data set will be available to future users of the biobank. To access data and biospecimens within the biobank, the prospective recipient executes a written Data User Agreement with the biobank, which will prohibit any attempts to re-identify subjects. Limited data will then be transmitted to prospective researchers using downloaded Excel compatible file formats. PHI will be maintained within the database as part of the consent process, in a partitioned and protected fashion (not available to future investigators) to permit the addition of updated clinical information into the biobank on a periodic basis. If for any reason the study is terminated, all data will be retained for six years, per CHOP policy A-3-9 for data retention. Following the end of data retention, data will be permanently de-coded and de-identified.
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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.
Miche Duvall contact
Kara N Maxwell, MD, PhD principal investigator
University of Pennsylvania
Suzanne MacFarland, MD principal investigator
Children's Hospital of Philadelphia
2 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 Li-Fraumeni-Like Syndrome, run by Abramson Cancer Center at Penn Medicine at 2 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 13 inclusion and 3 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 4 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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 Kara N Maxwell, MD, PhD (215-898-9698, LFS@pennmedicine.upenn.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Descriptive clinical data of all patients with confirmed germline TP53 variants (time frame: Five years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 4 Sep 2026.