Li-Fraumeni Syndrome/TP53 Biobank

NCT04367246 | Recruiting DMC

• 3 other identifiers: UPCC 24919IRB 18-015810IRB 834147
• Study Type: observational
• Target: 300
• Locations: 1 country
• Sites: 2

Brief 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. 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.

Conditions

Li-Fraumeni Syndrome; Li-Fraumeni-Like Syndrome

Keywords

TP53; TP53 Mutation

Outcome Measures

Primary Outcomes (3)

• 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.

  Five years

• Genomic landscape of TP53-associated tumors

  Five years

• Sequencing data from prospective blood collection and detection of ctDNA in plasma

  Five years

Secondary Outcomes (2)

• Utility of ctDNA assay in detection of cancer development in LFS patients

  Five years

• Genotype-phenotype correlations in patients with inherited TP53 mutations

  Five years

Study Arms (3)

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.

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.

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.

Other: No Intervention

Interventions

No Intervention OTHER

No intervention is assigned.

Affected Patients; Family Members; Household Members

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with LFS/ LFL, family members, and household members

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Abramson Cancer Center at Penn Medicine: lead
• Children's Hospital of Philadelphia: collaborator

Study Sites (2)

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Children's Hospital of Philadelphia

Phildelphia, Pennsylvania, 19104, United States

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

For affected patients (group 1), collection of biospecimens will occur either once (i.e., blood, buccal swabs, urine, skin fibroblasts), or every six months (i.e., plasma from blood, stool samples, and other specimens that are obtained and leftover as part of clinical care) . Unaffected family members (group 2) and household members (group 3) will only have samples requested once as per Schedule of Study Procedures (Group 3 subjects will not be asked for a germline specimen). None of these procedures are required for the subjects to participate in the study. Children \<18 years will complete procedures at CHOP, and adult participants will complete study procedures at PENN (adolescents and young adults seen at CHOP clinically may have their samples collected at CHOP even if over 18 years).

MeSH Terms

Conditions

Li-Fraumeni Syndrome; Li-Fraumeni-Like Syndrome

Condition Hierarchy (Ancestors)

Neoplastic Syndromes, Hereditary; Neoplasms; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; DNA Repair-Deficiency Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Kara N Maxwell, MD, PhD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

• Suzanne MacFarland, MD

  Children's Hospital of Philadelphia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kara N Maxwell, MD, PhD

CONTACT

215-898-9698; LFS@pennmedicine.upenn.edu

Miche Duvall

CONTACT

LFS@chop.edu

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 5 Years
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: April 27, 2020
• First Posted: April 29, 2020
• Study Start: September 24, 2019
• Primary Completion (Estimated): September 24, 2029
• Study Completion (Estimated): September 24, 2029
• Last Updated: August 14, 2025

Record last verified: 2025-08

Locations

US (2)