Recruiting

Observational Study

Sponsor:

Abramson Cancer Center at Penn Medicine

Code:

NCT04367246

Conditions

Li-Fraumeni Syndrome

Li-Fraumeni-Like Syndrome

Eligibility Criteria

Sex: All

Age: 0+

Healthy Volunteers: Accepted

Interventions

No Intervention

Study Details

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

Study ID

NCT04367246

Start date

Sep 24, 2019

Status verified date

Sep, 2026

Completion date

Sep 24, 2029

Anticipated

Primary completion date

Sep 24, 2029

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 0+

Healthy Volunteers: Accepted

Inclusion Criteria:

Affected Patient (Group 1)

1. Males or females aged 0 and above.
2. 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.
3. 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)

1. Males or females aged 0 and above.
2. Biological relative of subjects with germline TP53 mutation or variant (LFS), including first degree (siblings, parents) and second degree (grandparents, aunts, uncles) relatives.
3. Negative for germline TP53 mutation or variant.
4. 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)

1. Males or females aged 0 and above.
2. 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.
3. 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.

Exclusion Criteria:

1. Parents/LAR or subjects who, in the opinion of the Investigator, may be non-compliant with study schedules or procedures.
2. 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.

Study Design

Enrollment

300 participants

Anticipated

Interventions and Outcome Measures

Arms

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.

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.

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.

Interventions

No Intervention

No intervention is assigned.

Primary outcome measure

  • Descriptive clinical data of all patients with confirmed germline TP53 variants [ Time Frame: Five years ]
  • 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 ]

Central Contacts and Locations

Central contacts

Kara N Maxwell, MD, PhD

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

Miche Duvall

LFS@chop.edu

Locations

University of Pennsylvania

Recruiting

Philadelphia, Pennsylvania, United States, 19104

Contacts

Kara N Maxwell, MD, PhD

LFS@pennmedicine.upenn.edu

Principal Investigator:

Kara N Maxwell, MD, PhD

Children's Hospital of Philadelphia

Recruiting

Phildelphia, Pennsylvania, United States, 19104

Contacts

Suzanne P MacFarland, MD

LFS@chop.edu

Principal Investigator:

Suzanne P MacFarland, MD

More Information

Sponsor

Abramson Cancer Center at Penn Medicine

Last update posted

Sep 4, 2026

Last verified

Sep, 2026

Keywords

  • TP53
  • TP53 Mutation

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Abramson Cancer Center at Penn Medicine on 2026-09-04.