Surveillance for Malignant Transformation of Neurofibromatosis Type 1 (NF1) Related Peripheral Nerve Sheath Tumors (PNST)

Neurofibromatosis 1 Clinical Trial

Official title: Surveillance for Malignant Transformation of Neurofibromatosis Type 1 (NF1) Related Peripheral Nerve Sheath Tumors (PNST)

Status Not yet recruiting

Clinical Trial Summary

Background:

Neurofibromatosis type 1 (NF1) is a genetic disease that can cause many symptoms. About half of people with NF1 will develop benign (noncancerous) tumors along nerves in the skin, brain, and other parts of the body. Sometimes, though, these tumors can become cancerous. Researchers do not yet know how to predict which tumors will become cancerous.

Objective:

To test a new method for predicting which benign NF1 tumors will become cancerous.

Eligibility:

People aged 3 years and older with a clinical or genetic diagnosis of NF1.

Design:

• Participants will be screened with a review of their medical history. All participants will have a baseline visit. They will have bood tests and imaging scans. They will have a physical exam. They will answer questions about their family history. Participants aged 8 years and older will take tests of their thinking skills and their emotional health.

• Some participants may be asked to undergo more tests. These may include another type of imaging scan and a biopsy: A small sample of tissue may be removed from the tumor.

• Participants will be divided into two groups: those believed to be at low risk and those believed to be at high risk of developing cancer.

• Participants in the high-risk group will be asked to return for their next visit in 1 month to 3 years.

• Participants in the low-risk group will be asked to return for their next visit in 6 months to 5 years.

• Participants may also have follow-up visits by phone throughout the study. They will be in the study for 10 years.

Clinical Trial Description

Background

• Patients with NF1 are at risk for the development of both benign and malignant peripheral nerve sheath tumors (MPNST). Some factors that increase risk for malignant tumors are known, such as large benign plexiform neurofibroma (PN) tumor burden, germline NF1 microdeletion, and history of radiation therapy. However, there is not currently a consensus in the field about the most appropriate clinical surveillance or management strategy for these patients at increased risk of malignancy.

• In the past decade, data from the existing NCI POB NF1 Natural History study (08-C-0079, NCT00924196) and others have identified atypical neurofibromas (AN) and atypical neurofibromatous neoplasms of uncertainly biologic potential (ANNUBP) as premalignant lesions characterized by heterozygous loss of CDKN2A/B in addition to the homozygous loss of NF1 found in all PN.

• On Magnetic Resonance Imaging (MRI), distinct nodular lesions (DNL) have been identified as having unique characteristics, including increased fluorodeoxyglucose (FDG)-positron emission tomography (PET) avidity and growth rate compared to surrounding PN, and are often, though not always, found to be AN on histologic evaluation.

Objective

• To assess the feasibility of the study algorithm in identifying ANs, ANNUBPs, CDKN2A/B mutated lesions, and/or MPNST

Eligibility

• Participants aged >= 3 years old with a clinical or genetic diagnosis of NF1.

• Participants will be enrolled in one of the following cohorts:

• For the High-Risk Cohort one of the following criteria: microdeletion or 844-848 missense variants or other variants associated with increased risk of MPNST, family history of MPNST/ANNUBP/AN, personal history of MPNST/ANNUBP/AN or neurofibroma with CDKN2A/B loss, prior radiation therapy at any site, large PN burden (>= 350 mL), or presence >= 1 DNL at baseline.

• For the Low-Risk Cohort: none of the criteria noted for the high-risk cohort beyond NF1 diagnosis.

Design

• This is a Natural History Study to identify risk factors associated with severe disease in NF1 and to assess the feasibility of a novel NF1 Increased MPNST Risk Surveillance and Management Algorithm to aid in the surveillance and management of participants with NF1.

• 225 participants will be enrolled in this study. ;

Related Conditions & MeSH terms

• Nerve Sheath Neoplasms
• Neurofibroma
• Neurofibromatoses
• Neurofibromatosis 1

• NCT number: NCT06222203
• Study type: Observational
• Source: National Institutes of Health Clinical Center (CC)
• Contact: Jennifer Derise
• Phone: (240) 575-8520
• Email: jennifer.derise@nih.gov
• Status: Not yet recruiting
• Start date: June 26, 2024
• Completion date: December 31, 2035