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Investigator(s):
Brigitte Widemann, M.D. Principal Investigator Phone: 301-496-7387 widemanb@pbmac.nci.nih.gov
Referral Contact(s):
Pediatric Oncology  Phone: 1-877-624-4878 (Toll free)

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Primary Eligibility:

• Histologically confirmed* neurofibromatosis 1 (NF1) and plexiform neurofibromas (PNs) that are inoperable AND have the potential to cause significant morbidity including, but not limited to, any of the following:
• Head and neck lesions that could compromise the airway or great vessels
• Brachial or lumbar plexus lesions that could cause nerve compression and loss of function
• Lesions that could result in major deformity (e.g., orbital lesions) or significant cosmetic problems
• Lesions of the extremity that could cause limb hypertrophy or loss of function
• Painful lesions



[*Note: Histologic confirmation of tumor is not necessary in the presence of consistent clinical and radiographic findings, but should be considered if malignant degeneration of a PN is clinically suspected.]

• Must have either positive genetic testing for NF1 OR at least one other diagnostic criterion (according to NIH Consensus Conference criteria), including any of the following:
• ≥ 6 cafe-au-lait spots (≥ 0.5 cm in prepubertal subjects or ≥ 1.5 cm in post pubertal subjects)
• Freckling in axilla or groin
• Optic glioma
• ≥ 2 Lisch nodules
• Distinctive bony lesion (dysplasia of the sphenoid bone or dysplasia or thinning of long bone cortex)
• First-degree relative with NF1
• Measurable disease, defined as ≥ 1 unidimensionally measurable PN ≥ 3 cm
• Patients who have undergone surgery for resection of a PN are eligible provided the PN was incompletely resected and is measurable as defined above
• Complete tumor resection is not feasible or patient refused surgery
• No evidence of an optic glioma, malignant glioma, malignant peripheral nerve sheath tumor, or other cancer requiring treatment with chemotherapy or radiotherapy
• ≥ 3 years and ≤ 18 years of age
• Karnofsky or Lansky performance status 50–100%
• ANC ≥ 1,500/μL, hemoglobin ≥ 9 g/dL, and platelet count ≥ 100,000/μL
• PT and PTT ≤ 1.5 x upper limit of normal (ULN)
• Bilirubin within ULN for age, with the exception of Gilbert syndrome
• ALT, serum lipase, and amylase within ULN for age
• Creatinine clearance ≥ 60 mL/min OR serum creatinine normal based on age
• Not pregnant or nursing; fertile patients must use effective contraception
• No cytochrome P450 enzyme-inducing antiepileptic drugs for 7 days prior to enrollment in trial
• Recovered from prior therapy
• Able to swallow tablets
• No baseline hypertension (≥ 95th percentile for age and gender)
• No inability to undergo MRI and/or contraindication for MRI examinations in accordance with the MRI protocol
• No prior sorafenib
• No history of NF1-related cerebral vascular anomaly
• No growth factors that support platelet or white cell number or function within 7 days of enrolling in study
• No arterial or venous thrombosis within the past 3 months, no significant hemorrhage (i.e., hemoptysis, melena, or hematemesis) within the past 2 weeks, and no history of bleeding diathesis
• No requirement for systemic full-dose anticoagulation with systemic thrombolytics, heparin, coumadin, or low molecular weight heparin or other anticoagulants for therapy of active thrombosis within the past 3 months
• No clinically significant uncontrolled unrelated systemic illness such as serious infections or significant cardiac, pulmonary, hepatic, or other organ dysfunction

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Treatment Plan:

This is a multicenter study.

• Patients receive oral sorafenib tosylate twice daily on Days 1–28 (1 treatment cycle)
• Disease status will be evaluated using volumetric MRI analysis at regular intervals
• Patients with no documented disease progression or maximum radiographic response within the past 2 years continue treatment for up to 6 months in the absence of disease progression or unacceptable toxicity
• All other patients continue treatment for as long as benefit is shown
• Cognitive function and quality of life outcomes will also be assessed in a pilot fashion to define measures to be used in subsequent phase II trials
• After completion of study therapy, patients are followed at 30 days

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Additional Information:

• This trial will be conducted at the NIH Clinical Center in Bethesda, MD. It is open to patients who meet the eligibility requirements, regardless of where they live in the United States.
• There is no charge for medical care received at NIH Clinical Center.
• PDQ (Physicians Data Query) - provides additional details about this study for health care providers.

Reviewed: 11/12/08
Updated: 9/16/08