Neurofibromatosis 1NCT06222203
Surveillance for Malignant Transformation of Neurofibromatosis Type 1 (NF1) Related Peripheral Nerve Sheath Tumors (PNST)
An observational study of Neurofibromatosis 1 and Nerve Sheath Neoplasms, run by National Cancer Institute (NCI) at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 3 to 120 years
- Conditions the study is for
- Neurofibromatosis 1, Nerve Sheath Neoplasms
- How many people
- 225 participants
- Where
- 1 siteUnited States
- Study dates
- 9 Oct 2024to 31 Dec 2035
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 to 120 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
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.
Who may be able to join
- 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)
Show all 15Show fewer
- 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.
- 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.
Who cannot join
- High-Risk and Low-Risk NF1 Cohorts
- Inability or unwillingness to undergo MRI imaging
- Parent Cohort
- None.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
National Cancer Institute Referral Office, 888-624-1937
About this study
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.
Read more
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.
- Conditions
- Neurofibromatosis 1, Nerve Sheath Neoplasms
- Keywords
- NF1, atypical neurofibromas, Plexiform Neurofibromas, neurofibromas, PN, MPNST, malignant transformation, distinct nodular lesion
- Medical subject headings
- Neurofibromatosis 1, Nerve Sheath Neoplasms, Neurofibroma, Plexiform, Neurofibroma, Neurofibrosarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: Throughout the study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jan 2024
- Study start9 Oct 2024
- Primary completion31 Dec 2034 (estimated)
- Study completion31 Dec 2035 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Neurofibromatosis 1Studies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 225 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Brigitte C Widemann, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06222203
- Sponsor's protocol ID
- 10001696
- Other IDs
- 001696-C
- Status last verified
- 30 Oct 2026
- First submitted
- 23 Jan 2024
- Last updated
- 3 Nov 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- 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.
Study at a glance
From the registry record, last updated by the sponsor on 3 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Surveillance for Malignant Transformation of Neurofibromatosis Type 1 (NF1) Related Peripheral Nerve Sheath Tumors (PNST)
- ClinicalTrials.gov ID
- NCT06222203
- Acronym / sponsor ID
- 10001696
- Conditions
- Neurofibromatosis 1, Nerve Sheath Neoplasms
- Keywords
- NF1, atypical neurofibromas, Plexiform Neurofibromas, neurofibromas, PN, MPNST, malignant transformation, distinct nodular lesion
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 225 participants (estimated)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 9 Oct 2024 (actual)
- Primary completion
- 31 Dec 2034 (estimated)
- Study completion
- 31 Dec 2035 (estimated)
- First posted
- 24 Jan 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 3 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- 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.
Key inclusion criteria (15 listed)
- 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:
Key exclusion criteria (4 listed)
- High-Risk and Low-Risk NF1 Cohorts
- Inability or unwillingness to undergo MRI imaging
- Parent Cohort
- None.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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
Proportion of lesions that undergo surgical intervention (biopsy or resection) that are ANs, ANNUBPs, CDKN2A/B mutated lesions and/or MPNST
1 secondary outcome
Assess whether the proposed surveillance and management approach for participants with NF1 at high risk and low risk of MPNST is feasible
Time frame: Throughout the study
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Nov 2026.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Brigitte C Widemann, M.D. principal investigator
National Cancer Institute (NCI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Neurofibromatosis 1 and Nerve Sheath Neoplasms, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 3 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jennifer E Derise ((240) 575-8520, jennifer.derise@nih.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the 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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Nov 2026.