CClinicalTrials.gg
Sign In
RecruitingNCT06222203Updated Sep 2, 2026

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

An observational study in Neurofibromatosis 1 and Nerve Sheath Neoplasms, sponsored by National Cancer Institute (NCI). Recruiting at 1 site in United States. Open to participants aged 3 Years to 120 Years. Per ClinicalTrials.gov, last updated 2026-09-02.

Sponsored by National Cancer Institute (NCI) · Observational

Study type
Observational
Model
Cohort
Time perspective
Prospective
Enrollment
225
Ages
3 Years to 120 Years
Sex
All
01

Study 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.
Read the detailed 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 an observational 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.
02

Conditions studied

  • Neurofibromatosis 1
  • Nerve Sheath Neoplasms

Keywords

  • NF1
  • atypical neurofibromas
  • Plexiform Neurofibromas
  • neurofibromas
  • PN
  • MPNST
  • malignant transformation
  • distinct nodular lesion
03

Who can participate

Ages eligible
3 Years to 120 Years
Sexes eligible
All
Accepts healthy volunteers
No
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.

Eligibility criteria

  • INCLUSION CRITERIA:

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/B 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.

EXCLUSION CRITERIA:

High-Risk and Low-Risk NF1 Cohorts

- Inability or unwillingness to undergo MRI imaging

INCLUSION CRITERIA:

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.

EXCLUSION CRITERIA:

Parent Cohort

- None.

04

Study design

Observational model
Cohort
Time perspective
Prospective
Enrollment
225 participants (estimated)

Groups and cohorts

  • 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

05

What researchers measure

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/B mutated lesions and/or MPNST

    Time frame: 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

    Number of participants complying with recommendations for imaging/surgical interventionsNumber of resections recommended vs successfully completedProportion of subjects from the low-risk cohort that transition to the high- risk algorithm during the study observation periodThe number of subjects who develop high grade MPNST during the observation periodNumber of subjects who develop high grade MPNST outside of a pre-existing DNL or PN during the observation periodData from the Tumor Specific Risk Factor and Participant Specific Risk Factor Checklists

    Time frame: Throughout the study

06

Study locations

1 of 1 sites recruiting
  • National Institutes of Health Clinical Center
    Bethesda, Maryland 20892, United States
    • National Cancer Institute Referral Office · Contact · 888-624-1937
    Recruiting
07

References and documents

Individual participant data

Plan to share: Yes — All IPD recorded in the medical record will be shared with intramural investigators upon request. In addition, all large scale genomic sequencing data will be shared with subscribers to dbGaP.

Supporting information: Study protocol, Sap

08

Registry details

Key details

Study ID
NCT06222203
Lead sponsor
National Cancer Institute (NCI)
Responsible party
Sponsor
First posted
Jan 24, 2024
Start date
Oct 9, 2024
Primary completion
Dec 31, 2034 (estimated)
Completion
Dec 31, 2035 (estimated)
Last update
Sep 2, 2026

Study contacts

Jennifer E Derise
Contact
jennifer.derise@nih.gov
(240) 575-8520
Brigitte C Widemann, M.D.
Contact
widemanb@mail.nih.gov
(240) 760-6203
Brigitte C Widemann, M.D.
principal investigator · National Cancer Institute (NCI)

Oversight

FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Interested in this study?

Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.

Contact study team

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

Neurofibromatosis 1→

Other studies from this sponsor

National Cancer Institute (NCI)

Start the discussion