An observational study in Neurofibromatosis Type 1, Malignant Peripheral Nerve Sheath Tumor and Plexiform Neurofibroma, sponsored by National Cancer Institute (NCI). Active, not recruiting at 1 site in United States. Open to participants aged 4 Weeks and older. Per ClinicalTrials.gov, last updated 2026-09-24.
Sponsored by National Cancer Institute (NCI) · Observational
Background:
Neurofibromatosis Type 1 (NF1) is a genetic disorder in which patients are at increased risk of developing tumors (usually non-cancerous) of the central and peripheral nervous system. The disease affects essentially every organ system.
The natural course of NFI over time is poorly understood. For most patients the only treatment option is surgery. A better understanding of NF1 may be helpful for the design of future treatment studies.
Objectives:
To evaluate people with NF1 over 10 years in order to better understand the natural history of the disease.
To characterize the patient population and to examine how NFI affects patients quality of life and function.
Eligibility:
Children, adolescents, and adults with NF1.
Design:
Participants have a comprehensive baseline evaluation including genetic testing, tumor imaging, pain and quality-of-life assessments, and neuropsychological, motor and endocrine evaluations.
Patients are monitored every 6 months to every 3 years, depending on their individual findings at the baseline study. Tests may include the following, as appropriate:
Background
Neurofibromatosis Type 1 (NF1) is an autosomal dominant, progressive genetic disorder characterized by diverse clinical manifestations. Patients with NF1 have an increased risk of developing tumors of the central and peripheral nervous system including plexiform neurofibromas (PN), dermal neurofibromas, optic pathway tumors, brain tumors, malignant peripheral nerve sheath tumors (MPNST), juvenile myelomonocytic leukemia, and pheochromocytomas. In addition, NF1 manifests in essentially every organ system, with for example, skeletal and vascular abnormalities, and cognitive deficits. Thus, the care for individuals with NF1 requires a multidisciplinary approach. The natural history of NF1 related tumor and other manifestations is poorly understood, and for most NF1 related tumor manifestations the only standard treatment option is surgery. The NIH Clinical Center provides the ideal infrastructure for evaluation of the natural history of rare diseases. A better understanding of the natural history of NF1 related tumor and other manifestations will be helpful for the design of treatment studies. The NCI, POB has an active clinical trials program for NF1 related tumor manifestations including PN, MPNST. Unlike individuals with refractory solid cancers, individuals with NF1 have near normal life expectancy, and their benign tumors progress more slowly than solid cancers. Individuals with NF1 may thus participate in multiple treatment trials.
Objectives
The overall purpose of this descriptive NF1 Natural History study is to serve as an umbrella protocol for the ongoing NF1 clinical trials program to allow the longitudinal evaluation of individuals with NF1 for NF1 related tumor and non-tumor manifestations irrespective whether they are currently enrolled on a treatment study or not, and to develop a better understanding of the biology of NF1 related manifestations. Following these patients longitudinally will allow investigators to develop a better understanding of the natural history of these manifestations, provide the basis for the development of endpoints for clinical trials and to potentially develop more effective treatments. NF1 manifestations, which will be followed longitudinally, include PN, MPNST, optic pathway tumors, dermal neurofibromas, NF1 associated pain, and neuropsychological, motor, and endocrine function. Patient samples will be collected to investigate the existence of a peripherally detectable disease progression biomarker. A comprehensive treatment plan and recommendations will be developed and communicated with the patient and primary caregivers.
Eligibility
Children, adolescents, and adults with a confirmed clinical diagnosis of NF1 or a confirmed NF1 mutation.
Design
Attempts will be made to have all individuals undergo a comprehensive baseline evaluation including clinical phenotyping, genotyping, imaging of tumor manifestations, and pain, quality of life, neuropsychological, motor, and endocrine evaluations. The NF1 manifestations will be longitudinally monitored with a frequency of every year to every three years, with the extent and timing of follow-up evaluations depending on the findings at baseline.
Individuals with a confirmed clinical diagnosis of NF1 or a confirmed NF1 mutation; unaffected siblings and biologic parents of the individuals with NFI who enroll in the study.
INCLUSION CRITERIA:
Age:
Diagnosis: Patients who are diagnosed with NF1 using the NIH Consensus Conference criteria or have a confirmed NF1 mutation with analysis performed in a CLIA-certified laboratory. NF1 mutation testing to confirm eligibility will not be performed on this protocol, but as part of a separate screening study. Histologic confirmation of NF1 related benign tumors is not necessary in the presence of consistent clinical and radiographic findings but is required for individuals with MPNST who enroll on this study.
For the clinical diagnosis of NF1 all study subjects must have at two or more diagnostic criteria for NF1 listed below (NIH Consensus Conference):
EXCLUSION CRITERIA:
Biologic parents of children and adults with NFI will be evaluated at one time point, using a Neuropsychological Test Battery and QOL Assessment. Closed to enrollment
Children and adults with NFI whose tumor and non tumor related manifestations will be longitudinally evaluated. Closed to enrollment
Unaffected siblings of children and adults with NFI will be evaluated at one time point using a Neuropsychological Test Battery and QOL Assessment. Closed to enrollment
To serve as an umbrella protocol for the ongoing NF1 clinical trials program to longitudinally characterize and analyze NF1 related tumor and non-tumor manifestations, and to develop a better understanding of the biology of NF1 related manifesta...
Characterized features will be described and presented.
Time frame: throughout the study
Plan to share: Yes — All IPD recorded in the medical record will be shared with intramural investigators upon request.
Supporting information: Study protocol, Sap, Icf
This study is active, not recruiting, as verified in Sep 2026. You cannot join it, but the record below documents what was studied.
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National Cancer Institute (NCI)