- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04367246
Li-Fraumeni Syndrome/TP53 Biobank
Clinical and Molecular Studies of Li-Fraumeni Syndrome and TP53-associated Disorders
Study Overview
Status
Conditions
Intervention / Treatment
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 Type
Enrollment (Anticipated)
Contacts and Locations
Study Contact
- Name: Kara N Maxwell, MD, PhD
- Phone Number: 215-898-9698
- Email: LFS@pennmedicine.upenn.edu
Study Contact Backup
- Name: Miche Duvall
- Email: LFS@chop.edu
Study Locations
-
-
Pennsylvania
-
Philadelphia, Pennsylvania, United States, 19104
- Recruiting
- University of Pennsylvania
-
Contact:
- Kara N Maxwell, MD, PhD
- Email: LFS@pennmedicine.upenn.edu
-
Principal Investigator:
- Kara N Maxwell, MD, PhD
-
Philadelphia, Pennsylvania, United States, 19104
- Recruiting
- Children's Hospital of Philadelphia
-
Contact:
- Suzanne P MacFarland, MD
- Email: LFS@chop.edu
-
Principal Investigator:
- Suzanne P MacFarland, MD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion Criteria:
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.
Exclusion Criteria:
- 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.
Study Plan
How is the study designed?
Design Details
- Observational Models: Cohort
- Time Perspectives: Prospective
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
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.
|
No intervention is assigned.
|
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.
|
No intervention is assigned.
|
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.
|
No intervention is assigned.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Five years
|
Genomic landscape of TP53-associated tumors
Time Frame: Five years
|
Five years
|
|
Sequencing data from prospective blood collection and detection of ctDNA in plasma
Time Frame: Five years
|
Five years
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Utility of ctDNA assay in detection of cancer development in LFS patients
Time Frame: Five years
|
Five years
|
Genotype-phenotype correlations in patients with inherited TP53 mutations
Time Frame: Five years
|
Five years
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Kara N Maxwell, MD, PhD, University of Pennsylvania
- Principal Investigator: Suzanne MacFarland, MD, Children's Hospital of Philadelphia
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- UPCC 24919
- IRB 18-015810 (Other Identifier: Children's Hospital of Philadelphia)
- IRB 834147 (Other Identifier: University of Pennsylvania)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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