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Protocol Details

Natural History Study and Longitudinal Assessment of Children, Adolescents, and Adults with Neurofibromatosis Type 1

This study is NOT currently recruiting participants.

Summary | Eligibility | Citations | Contacts




Sponsoring Institute

National Cancer Institute (NCI)

Recruitment Detail

Type: No longer recruiting/follow-up only
Gender: Male & Female
Min Age: 4 wk
Max Age: N/A

Referral Letter Required


Population Exclusion(s)



Plexiform Neurofibroma;
Optic Pathway Tumor;
Malignant Peripheral Nerve Sheath Tumor;
Volumetric MRI;
Natural History

Recruitment Keyword(s)

Neurofibromatosis Type 1;
Optic Glioma;
Plexiform Neurofibroma


Neurofibromatosis Type 1;
Malignant Peripheral Nerve Sheath Tumor;
Plexiform Neurofibroma;
Optic Glioma;

Investigational Drug(s)


Investigational Device(s)




Supporting Site

National Cancer Institute


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.


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.


Children, adolescents, and adults with NF1.


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:

-Medical history, physical examination and blood tests.

-Whole body and face photography to monitor visible deformities.

-Neuropsychological testing, quality-of-life evaluations, motor function tests, endocrinologic evaluations, heart and lung function tests, hearing tests, bone density scans and other bone evaluations.

-MRI and PET scans to detect and assess plexiform neurofibromas (tumors that arise from nerves and can cause serious problems), paraspinal neurofibromas (tumors that arise from nerves around the spine and can cause problems by compressing the spinal cord), and malignant peripheral nerve sheath tumors (a type of cancer that arises from a peripheral nerve or involves the sheath covering the nerve).

-Eye exams, MRI scans and PET scans to evaluate optic pathway gliomas (tumors arising from the vision nerves or the brain areas for vision) and the chemicals within the tumor and brain.

-Eye exams and photographs to evaluate the development of Lisch nodules (non-cancerous tumors on the eye).

-Photographs of dermal neurofibromas (tumors of the skin), cafe-au-lait spots (dark or pigmented areas on the skin that are often the first signs of NF1) and other skin problems.

-Pain evaluations to monitor the different types of pain patients experience, causes of the pain, how often the pain occurs, effect of the pain on quality of life, and what pain medications and alternative treatments, such as acupuncture, are effective.

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1. Age:

- Less than or equal to 35 years of age for new patients evaluated at NIH.

- No upper age limit for patients previously enrolled on clinical trials at NIH or for patients diagnosed with MPNST, or with clinical concern for MPNST, or with infrequent or unusual NF1 related manifestations.

2. 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 least two or more diagnostic criteria for NF1 listed below (NIH Consensus Conference):

a. Six or more cafe-au-lait spots (greater than or equal to 0.5 cm in prepubertal subjects or greater than or equal to 1.5 cm in postpubertal subjects).

b. Greater than or equal to 2 neurofibromas or 1 plexiform neurofibroma.

c. Freckling in the axilla or groin.

d. Optic glioma.

e. Two or more Lisch nodules.

f. A distinctive bony lesion (dysplasia of the sphenoid bone or dysplasia or thinning of long bone cortex).

g. A first-degree relative with NF1.

3. Prior and current therapy: For NF1 related benign tumor manifestations there is no standard effective medical treatment, and surgery is the only standard treatment. Chemotherapy and radiation therapy are additional treatment options for malignant NF1 related tumors. For the purpose of this study, subjects who have not previously received medical or surgical treatment, patients, who have previously received medical or surgical treatment, and patients who are currently receiving medical treatment and/or radiation for a NF1 related manifestation will be eligible. Prior and current treatment for NF1 related manifestations will be recorded at trial entry and throughout the study.

4. Performance Status: ECOG less than or equal to 3. Subjects who are wheelchair bound because of paralysis will be considered ambulatory when they are up in their wheelchair. Subjects have to be able to travel to the NIH for evaluations.

5. Informed Consent: All patients or their legal guardians (if the patient is less than 18 years old) must sign an IRB-approved document of informed consent to demonstrate their understanding of the investigational nature and the risks of this study before any protocol-related studies are performed. When appropriate, pediatric subjects will be included in all discussions.


1. In the opinion of the investigator the patient is not able to return for follow-up visits or obtain required follow-up studies.

2. In the opinion of the investigator the patient is not able to obtain an MRI scan.

3. Individuals who are pregnant or breast feeding or who become pregnant while enrolled on this trial will not be excluded from participation, but will not undergo radiographic evaluations or MRI scans requested for research purposes, or other studies which might negatively impact on the pregnancy.

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Ferner RE.Neurofibromatosis 1 and neurofibromatosis 2: a twenty first century perspective.Lancet Neurol. 2007 Apr;6(4):340-51.

Korf BR. Clinical features and pathobiology of neurofibromatosis 1. J Child Neurol. 2002 Aug;17(8):573-7; discussion 602-4, 646-51.

Kim A, Gillespie A, Dombi E, Goodwin A, Goodspeed W, Fox E, Balis FM, Widemann BC. Characteristics of children enrolled in treatment trials for NF1-related plexiform neurofibromas. Neurology. 2009 Oct 20;73(16):1273-9. doi: 10.1212/WNL.0b013e3181bd1326. PMID: 19841379; PMCID: PMC2764415.

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Principal Investigator

Referral Contact

For more information:

Brigitte C. Widemann, M.D.
National Cancer Institute (NCI)
NIHBC 10 - CRC BG RM 1-3752
(240) 760-6203

Andrea (Andy) F. Gillespie, R.N.
National Cancer Institute (NCI)
National Institutes of Health
Building 10
Room 84DD
10 Center Drive
Bethesda, Maryland 20892
(240) 760-6185

NCI Referral Office
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Bethesda, Maryland 20892, United States: NCI Clinical Trials Referral Office

Clinical Trials Number:


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