Screening With Whole Body MRI For Detection Of Primary Tumors In Children And Adults With Li-Fraumeni Syndrome (LFS) And Other Cancer Predisposition Syndromes

Li-Fraumeni Syndrome Clinical Trial

Official title:

Screening With Whole Body MRI For Detection Of Primary Tumors In Children And Adults With Li-Fraumeni Syndrome (LFS) And Other Cancer Predisposition Syndromes

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02950987
• Other study ID #: 11-200
• Status: Active, not recruiting
• Phase: N/A
• Start date: March 2012
• Est. completion date: December 2024

Study information

• Verified date: June 2023
• Source: Dana-Farber Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is evaluating Whole Body MRI as a possible screening tool to diagnose cancer for people with LFS and other inherited cancer predisposition syndromes.

Description:

Individuals who carry the TP53 mutation have a higher risk of developing different types of cancer over their lifetimes. This gene has been associated with Li Fraumeni syndrome in some families, but not all families that have cancer histories consistent with Li Fraumeni syndrome will have the mutation. Currently, there is no standard method of monitoring LFS carriers, family members, or others individuals with cancer predisposition syndromes to detect cancers in the early stages, when they may be more easily treated. The main aim of the study is to test a relatively new medical technology called Whole Body Magnetic Resonance Imaging (MRI), in patients with these syndromes, to see if cancers can be detected at an early stage which may, in turn, allow for more effective treatment. The investigators have chosen Whole Body MRI scanning because this scan allows doctors to look at the entire body in one examination. By using this technology, participants are not exposed to radiation, which is of particular importance for individuals who have a higher cancer risk due to a diagnosis of LFS.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 150
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Adults
• Individuals greater than or equal to 18 years of age.
• Individuals with "Li Fraumeni Syndrome" defined as one of the following:
• Carriers of a germline p53 mutation
• Members of families meeting classic LFS criteria by family history without an identifiable p53 mutation
• Obligate carrier by pedigree (these individuals can be offered testing but are still eligible if they defer). The following examples describe "obligate carriers by pedigree."
• A child of a parent with known p53 mutation that is diagnosed with cancer
• An individual with a sibling and a child who are p53 positive -OR-
• Individuals with an inherited cancer predisposition syndrome as defined by one of the

following:

• Hereditary Retinoblastoma with a germline Rb mutation
• Diagnosis of Hereditary Paraganglioma/Pheochromocytoma Syndrome with a germline SDH mutation
• Diagnosis of Multiple Endocrine Neoplasia, Type 1 or 2, with a germline MEN mutation
• New diagnosis of opsoclonus-myoclonus with a negative cancer work-up upon presentation of symptoms
• Familial Neuroblastoma with a germline ALK mutation
• Rapid-onset Obesity with Hypothalamic dysfunction, Hypoventilation and Autonomic Dysregulation (ROHHAD syndrome) or Congenital central hypoventilation syndrome (CCHS) with or without a germline PHOX 2B mutation
• Von Hippel-Lindau with a VHL mutation
• Women with an abnormal cell-free DNA test (i.e. a non-invasive prenatal test (NIPT) to detect chromosomal abnormalities) and no cancer diagnosis
• Other rare cancer predisposition syndromes at the discretion of the treating physician and study physicians
• NOTE: Individuals with any of the above-listed cancer predisposition syndromes (apart from Li Fraumeni syndrome) are likewise eligible in the absence of a known mutation if they are an obligate carrier by pedigree.
• Individuals can have a prior history of cancer; these individuals must be in stable remission and at least 6 months out from the completion of surgery/radiation\ therapy/chemotherapy.
• Individual cases can be reviewed with the institutional principal investigator.
• Individuals not pregnant at enrollment. Female subjects of childbearing potential will undergo a pregnancy test prior to imaging.
• Individuals able to give informed consent or a signature from a designated health care proxy or legal guardian. Children
• Individuals who are less than 18 years of age
• Individuals with "Li Fraumeni Syndrome" defined as one of the following:
• Carriers of a germline p53 mutation OR
• Members of families meeting classic LFS criteria by family history without an identifiable p53 mutation OR
• Obligate carrier by pedigree (these individuals can be offered testing but are still eligible if they defer). The following examples describe "obligate carriers by pedigree."
• A child of a parent with known p53 mutation that is diagnosed with cancer
• An individual with a sibling and a child who are p53 positive -OR-
• Individuals with an inherited cancer predisposition syndrome as defined by one of the

following:

• Hereditary Retinoblastoma with a germline Rb mutation
• Diagnosis of Hereditary Paraganglioma/Pheochromocytoma Syndrome with a germline SDH mutation
• Diagnosis of Multiple Endocrine Neoplasia, Type 1 or 2, with a germline MEN mutation
• New diagnosis of opsoclonus-myoclonus with a negative cancer work-up upon presentation of symptoms
• Familial Neuroblastoma with a germline ALK mutation
• Rapid-onset Obesity with Hypothalamic dysfunction, Hypoventilation and Autonomic Dysregulation (ROHHAD syndrome) or Congenital central hypoventilation syndrome (CCHS) with or without a germline PHOX 2B mutation
• Von Hippel-Lindau with a VHL mutation
• Other rare cancer predisposition syndrome at the discretion of the treating physician and study physicians
• NOTE: Individuals with any of the above-listed cancer predisposition syndromes (apart from Li Fraumeni syndrome) are likewise eligible in the absence of a known mutation if they are an obligate carrier by pedigree.
• Individuals can have a prior history of cancer; these individuals must be in stable remission and at least 6 months out from the completion of surgery/radiation therapy/chemotherapy. Individual cases can be reviewed with the institutional principal investigator.
• Individuals not pregnant at enrollment. Female subjects of childbearing potential will undergo a pregnancy test prior to imaging.
• Signed document of informed consent completed by the parent or legal guardian
• Signed document of assent obtained if child =10 years of age Exclusion Criteria: Adults and Children
• Active cancer or metastatic disease, except in the case of Stage 0 Chronic Lymphocytic Leukemia or nonmelanoma skin cancer.
• Patients with a contraindication to sedation or general anesthesia
• Patients with a metal heart valve, surgical clips, a pacemaker or any other indwelling metal device that might interfere with MRI
• Females who are pregnant or nursing

Related Conditions & MeSH terms

• Disease Susceptibility
• Li-Fraumeni Syndrome
• Syndrome

Intervention

Device:
• Whole Body MRI

Locations

Country	Name	City	State
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Dana-Farber Cancer Institute

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Return of pediatric and adult patients with Li Fraumeni Syndrome year-after-year for 4 annual scans.	Successful return of patients for four annual scans will be recorded.	4 years
Secondary	Return of pediatric and adult patients with other cancer predisposition syndromes year-after-year for 4 annual scans.	Successful return of patients for four annual scans will be recorded.	4 years
Secondary	Detection of prevalent and incident cancers on WB-MRI in pediatric and adult patients with Li Fraumeni and other inherited cancer predisposition syndromes.	Tabulation of all follow-up imaging studies, biopsies, and cancer diagnoses will be pursued.	3 years
Secondary	Detection of prevalent and incident cancers on additional screening studies in pediatric and adult patients with Li Fraumeni and other inherited cancer predisposition syndromes.	Tabulation of all follow-up imaging studies, biopsies, and cancer diagnoses will be pursued.	3 years