Natural History and Biology of Skin Neurofibromas in Neurofibromatosis Type 1

NCT00314119 | Completed

• 2 other identifiers: 06013406-C-0134
• Study Type: observational
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

This study will explore the growth of dermal neurofibromas (skin tumors) in patients with neurofibromatosis type 1 (NF1). Investigators will try to learn: 1) how fast (or slow) these benign tumors grow in NF1, 2) how often new tumors appear and 3) what genes are involved in the growth of the tumors. Men and women between 20 and 50 years of age diagnosed with NF1 and their biological parents are eligible for this study. Patients with NF1 are evaluated at the NIH Clinical Center with the following tests and procedures:

• Medical examination and drawing of family tree.
• Photos of the back, abdomen and thigh in order to count the number of skin tumors.
• Photos of the skin taken with a special camera (Primos camera) that takes very detailed pictures of a small area of skin.
• Photos of the skin taken with a dermatoscope, which takes very detailed pictures of a small area of skin under high magnification.
• Biopsy of at least one skin tumor and biopsy of a small piece of normal skin.
• Blood sample collection for genetic testing of the gene NF1 and to establish a cell line.
• Other medical tests (e.g., x-rays or MRI) if needed. Patients and their families will also have a genetic counseling session and an opportunity to ask questions about neurofibromatosis type 1. Patients return to the NIH after 3, 6, 12, 18 and 24 months for follow-up photographs and possibly blood samples. Biological parents of patients provide a blood sample for genetic testing.

Conditions

Neurofibromatosis Type 1; Neurofibroma

Keywords

Tumor Imaging; NF1; Natural History; Neurofibromatosis

Outcome Measures

Primary Outcomes (3)

• Quantify the growth of dermal neurofibromas in NF1 with 3 different imaging modalities.

  Evaluate the natural history of dermal neurofibromas in NF1 by monitoring the growth rate and development of new dermal neurofibromas using three different complementary imaging modalities over time in individuals with NF1. The study will be adequately powered so that a minimally meaningful statistical definition of progression can be developed for use in subsequent treatment protocols.

  12/31/2010

• Use an innovative gene expression method to identify genetic modifiers of dermal neurofibroma burden.

  Screen for genetic modifiers of dermal neurofibroma burden and growth using a novel approach employing the genetics of gene expression and family-based tests of association. Characterization of gene expression profiles in lymphoblastoid cell lines (LCLs) and dermal neurofibromas predictive of tumor behavior (e.g. growth rate) will also be explored.

  12/31/2010

• Evaluate dermal neurofibromas and normal skin for the presence of targets of sorafenib.

  Validate sorafenib as a rational agent for clinical development in individuals with NF1-related dermal neurofibromas. Quantify thelevel of expression of the targets of sorafenib by gene expression microarray of both normal skin and of the dermal neurofibromasthemselves. A tissue microarray from formalin-fixed neurofibromas may also be developed to investigate the expression of other therapeutic targets.

  12/31/2010

Study Arms (1)

1

Men and women between 20 and 50 years of age diagnosed with NF1 and their biological parents are eligible for this study.

Eligibility Criteria

• Age: 20 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Men and women between 20 and 50 years of age diagnosed with NF1 and their biological parents are eligible for this study.

You may qualify if:

• Clinical diagnosis of NF1. In order to meet the diagnosis of NF1 individuals must have 2 of the diagnostic criteria listed below:
• Six or more cafe-au-lait macules (greater than or equal to 0.5 cm in prepubertal subjects or greater than or equal to 1.5 cm in postpubertal subjects)
• Freckling in the axilla or groin
• A tumor of the optic pathway
• Two or more Lisch nodules
• A distinctive bony lesion (dysplasia of the sphenoid bone or dysplasia or thinning of long bone cortex)
• A plexiform neurofibroma or two or more neurofibromas
• A first-degree relative with NF1 by the above criteria
• We may request the medical records of potential enrollees for our review. Ideally, individuals will have been evaluated by a geneticist and a definitive diagnosis made. However given the unique, familial (and often unmistakable features) of NF1 it is likely the diagnosis can be reliably made by a non-geneticist.
• Age at study entry: 20- 50 years (inclusive)
• Identification of a physician who will be responsible for follow-up care, if needed
• Ability and willingness to travel to the NIH Clinical Center or University of Alabama at Birmingham Alabama for multiple evaluations
• Ability and willingness of both biologic parents to provide a blood (or saliva) sample
• Must have at least one dermal neurofibroma amenable to excisional biopsy. Preferably the neurofibroma will be on the thorax or abdomen and be at least the size of a pencil eraser.
• Biological parents (either affected or unaffected) of Group A individuals

You may not qualify if:

• Any history of administration (or current use) of radiation therapy, chemotherapeutic agents or biologic agents (experimental or not) that resulted in a documented significant change in dermal neurofibroma tumor burden or growth.
• Patients with probable segmental or mosaic NF1 will be excluded from study participation and medical records may be reviewed prior to enrollment for this determination.
• A history of administration of medications within 6 months of study entry that might reasonably be expected to alter the natural history of tumor growth (examples include pirfenidone, interferon, farnesyl transferase inhibitor (FTI), MTX/VBL, thalidomide, growth hormone) or cause significant changes in gene expression profile.
• Known or suspected untreated bleeding diathesis or platelet disorder that would preclude safe and successful dermal neurofibroma and skin biopsy. Patients prescribed aspirin or other known/suspected agent that interferes with platelet function may also be excluded if they cannot safely discontinue its use a week ahead of the biopsy.
• Clinically significant unrelated systemic illness, such as serious infection, hepatic, renal or other organ dysfunction, which in the judgment of the principal investigator or associate investigator would compromise the patient's ability to participate in the study procedures.
• Inability or unwillingness to tolerate the dermal neurofibroma excision and skin biopsy or blood draw.
• \) Cognitive delay to the extent that conscious sedation is required to obtain the dermal neurofibroma excision and skin biopsy.
• Biologic parents unable or unwilling to provide a blood (or saliva) sample.
• Inability to travel to the NIH or to The University of Alabama at Birmingham, AL
• Individuals refusing an excisional tumor or skin biopsy.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (1)

• Korf BR. Clinical features and pathobiology of neurofibromatosis 1. J Child Neurol. 2002 Aug;17(8):573-7; discussion 602-4, 646-51. doi: 10.1177/088307380201700806.

  PMID: 12403555 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Neurofibromatosis 1; Neurofibroma; Neurofibromatoses

Condition Hierarchy (Ancestors)

Nerve Sheath Neoplasms; Neoplasms, Nerve Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplastic Syndromes, Hereditary; Neurocutaneous Syndromes; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Peripheral Nervous System Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Peripheral Nervous System Neoplasms; Nervous System Neoplasms

Study Officials

• Douglas R Stewart, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 11, 2006
• First Posted: April 12, 2006
• Study Start: June 8, 2006
• Last Updated: April 14, 2026

Record last verified: 2025-07-14

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: At the time of a request and as long as needed.
• Access Criteria: De-identified clinical data will be shared with collaborators under appropriate agreements.

Locations

US (1)