Li-Fraumeni Syndrome/TP53 Biobank
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ClinicalTrials.gov Identifier: NCT04367246 |
Recruitment Status :
Recruiting
First Posted : April 29, 2020
Last Update Posted : February 27, 2023
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Condition or disease | Intervention/treatment |
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Li-Fraumeni Syndrome Li-Fraumeni-Like Syndrome | Other: No Intervention |
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 : | Observational [Patient Registry] |
Estimated Enrollment : | 300 participants |
Observational Model: | Cohort |
Time Perspective: | Prospective |
Target Follow-Up Duration: | 5 Years |
Official Title: | Clinical and Molecular Studies of Li-Fraumeni Syndrome and TP53-associated Disorders |
Actual Study Start Date : | September 24, 2019 |
Estimated Primary Completion Date : | September 24, 2024 |
Estimated Study Completion Date : | September 24, 2024 |
Group/Cohort | Intervention/treatment |
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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.
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Other: No Intervention
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.
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Other: No Intervention
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.
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Other: No Intervention
No intervention is assigned. |
- 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 ]
- 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 ]
Biospecimen Retention: Samples With DNA
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | Child, Adult, Older Adult |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | Yes |
Sampling Method: | Non-Probability Sample |
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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04367246
Contact: Kara N Maxwell, MD, PhD | 215-898-9698 | LFS@pennmedicine.upenn.edu | |
Contact: Miche Duvall | LFS@chop.edu |
United States, Pennsylvania | |
Children's Hospital of Philadelphia | Recruiting |
Philadelphia, Pennsylvania, United States, 19104 | |
Contact: Suzanne P MacFarland, MD LFS@chop.edu | |
Principal Investigator: Suzanne P MacFarland, MD | |
University of Pennsylvania | Recruiting |
Philadelphia, Pennsylvania, United States, 19104 | |
Contact: Kara N Maxwell, MD, PhD LFS@pennmedicine.upenn.edu | |
Principal Investigator: Kara N Maxwell, MD, PhD |
Principal Investigator: | Kara N Maxwell, MD, PhD | University of Pennsylvania | |
Principal Investigator: | Suzanne MacFarland, MD | Children's Hospital of Philadelphia |
Responsible Party: | Kara Maxwell, MD, PhD, Abramson Cancer Center at Penn Medicine |
ClinicalTrials.gov Identifier: | NCT04367246 |
Other Study ID Numbers: |
UPCC 24919 IRB 18-015810 ( Other Identifier: Children's Hospital of Philadelphia ) IRB 834147 ( Other Identifier: University of Pennsylvania ) |
First Posted: | April 29, 2020 Key Record Dates |
Last Update Posted: | February 27, 2023 |
Last Verified: | February 2023 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | Undecided |
Plan Description: | 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. |
Studies a U.S. FDA-regulated Drug Product: | No |
Studies a U.S. FDA-regulated Device Product: | No |
TP53 TP53 Mutation |
Li-Fraumeni Syndrome Syndrome Disease Pathologic Processes Neoplastic Syndromes, Hereditary |
Neoplasms Genetic Diseases, Inborn DNA Repair-Deficiency Disorders Metabolic Diseases |