Recruiting

Observational Study

Sponsor:

National Cancer Institute (NCI)

Code:

NCT06222203

Conditions

Neurofibromatosis 1

Nerve Sheath Neoplasms

Eligibility Criteria

Sex: All

Age: 3 - 70+

Healthy Volunteers: Not accepted

Study Details

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

Study ID

NCT06222203

Start date

Oct 9, 2024

Status verified date

Aug 28, 2026

Completion date

Dec 31, 2035

Anticipated

Primary completion date

Dec 31, 2034

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 3 - 70+

Healthy Volunteers: Not accepted

  • 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.

Study Design

Enrollment

225 participants

Anticipated

Interventions and Outcome Measures

Arms

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

Primary outcome measure

  • 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... [ Time Frame: Throughout the study ]

Central Contacts and Locations

Central contacts

Jennifer E Derise

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

Brigitte C Widemann, M.D.

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

Locations

National Institutes of Health Clinical Center

Recruiting

Bethesda, Maryland, United States, 20892

Contacts

National Cancer Institute Referral Office

888-624-1937

More Information

Sponsor

National Cancer Institute (NCI)

Last update posted

Sep 2, 2026

Last verified

Aug 28, 2026

Keywords

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

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by National Cancer Institute (NCI) on 2026-09-02.