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

NCT06222203 | Recruiting

• 2 other identifiers: 10001696001696-C
• Study Type: observational
• Target: 225
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Neurofibromatosis 1; Nerve Sheath Neoplasms

Keywords

NF1; atypical neurofibromas; Plexiform Neurofibromas; neurofibromas; PN; MPNST; malignant transformation; distinct nodular lesion

Outcome Measures

Primary Outcomes (1)

• Assess feasibility of the study algorithm in identifying atypical neurofibromas (ANs), atypical neurofibromatous neoplasms of unknown biologic potential (ANNUBPs), CDKN2A/B mutated lesions, and/or malignant peripheral nervous sheath tumors (MPNS...

  Proportion of lesions that undergo surgical intervention (biopsy or resection) that are ANs, ANNUBPs, CDKN2A mutated lesions and/or MPNST

  Throughout the study

Secondary Outcomes (1)

• Assess whether the proposed surveillance and management approach for participants with NF1 at high risk and low risk of MPNST is feasible

  Throughout the study

Study Arms (3)

1 - High-Risk

Participants with clinical or genetic diagnosis of NF1 AND at least one of the eligibility-required high-risk characteristics

2 - Low-Risk

Participants with clinical or genetic diagnosis of NF1 AND none of the eligibility-required high-risk characteristic

3 - Caregiver

Parents or guardians of participants 8-17 years old in High-Risk or Low-Risk Cohorts

Eligibility Criteria

• Age: 3 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Participants aged \>= 3 years old with a clinical or genetic diagnosis of NF1; parents or guardians of participants ages 8-17 years old.

You may qualify if:

• High-Risk and Low-Risk NF1 Cohorts
• Age \>= 3 years old
• Participants with clinical or genetic diagnosis of NF1.
• Participants with a diagnosis of mosaic or segmental NF1 are also eligible.
• Individuals may have (High-Risk Cohort) or not have (Low-Risk Cohort) at least one of the following characteristics:
• Microdeletion or 844-848 missense variants or other variants associated with increased risk of malignant peripheral nervous sheath tumor (MPNST)
• Family history of MPNST / atypical neurofibromatous neoplasm of unknown biologic potential (ANNUBP) / atypical neurofibromas (ANF)
• Personal history of MPNST/ANNUBP/ANF or neurofibroma with CDKN2A loss
• Prior radiation therapy at any site
• Large plexiform neurofibroma (PN) burden (\>= 350 mL)
• Presence \>= 1 DNL at baseline
• The ability of the individual, parent/guardian or Legally Authorized Representative (LAR) to understand and the willingness to sign a written consent document for participation.

You may not qualify if:

• High-Risk and Low-Risk NF1 Cohorts
• \- Inability or unwillingness to undergo MRI imaging
• Parent Cohort
• Parent or guardian of pediatric individuals (8-17 years old) in High-Risk or Low-Risk Cohorts.
• The ability of the parent/guardian or LAR to understand and the willingness to sign a written consent document for parent/guardian participation in this study.
• Parent Cohort
• \- None.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Neurofibromatosis 1; Nerve Sheath Neoplasms; Neurofibroma, Plexiform; Neurofibroma; Neurofibrosarcoma

Condition Hierarchy (Ancestors)

Neurofibromatoses; Neoplasms, Nerve Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplastic Syndromes, Hereditary; Neurocutaneous Syndromes; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Peripheral Nervous System Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Peripheral Nervous System Neoplasms; Nervous System Neoplasms; Fibrosarcoma; Neoplasms, Fibrous Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Sarcoma

Study Officials

• Brigitte C Widemann, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jennifer E Derise

CONTACT

(240) 575-8520; jennifer.derise@nih.gov

Brigitte C Widemann, M.D.

CONTACT

(240) 760-6203; widemanb@mail.nih.gov

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 23, 2024
• First Posted: January 24, 2024
• Study Start: October 9, 2024
• Primary Completion (Estimated): December 31, 2034
• Study Completion (Estimated): December 31, 2035
• Last Updated: September 26, 2025

Record last verified: 2025-09-24

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data from this study may be requested from other researchers after the completion of the primary endpoint. Genomic data are available once genomic data are uploaded per protocol GDS plan for as long as database is active.
• Access Criteria: Data from this study may be requested by contacting the PI. Genomic data are made available via dbGaP through requests to the data custodians.

Locations

US (1)