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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:

• Unresectable sporadic or neurofibromatosis type 1 (NF1)-associated high-grade malignant peripheral nerve sheath tumors (MPNSTs)
• Stage III or stage IV (metastatic) tumor
• Measurable disease, defined as at least one tumor that is measurable in two dimensions on CT or MRI scan
• No prior chemotherapy for MPNST; prior surgical resection permitted with residual or recurrent measurable disease
• Patients who develop a recurrence or progression (WHO criteria) of an MPNST in a previously radiated field may be enrolled if it has been at least 4 weeks since their last dose of radiation therapy (Note: Patients who have received radiation and have developed a local or metastatic recurrence outside of the radiation field are also eligible)
• Patients with NF1 can have undergone treatment of a plexiform neurofibroma, optical pathway tumor, or other NF1-associated tumor in the past with biologic agents or chemotherapy excluding ifosfamide, doxorubicin, and etoposide
• Recovered from toxic effects of all prior therapy
• Normal cardiac function
• Normal serum creatinine for age OR creatinine clearance > 60 mL/min/1.73 m²
• Adequate liver function
• Normal unsupported hematologic function
• Children and adults are eligible with no upper or lower age limit
• ECOG performance status of 0, 1, or 2
• Not pregnant or nursing; fertile patients must use effective contraception during and for 6 months after the completion of study treatment

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Study Outline:

This is a multicenter study. Patients are stratified according to type of malignant peripheral nerve sheath tumor (MPNST) (sporadic MPNST vs neurofibromatosis type 1 [NF1]-associated MPNST). Patients receive one of two treatment regimens depending on the location of the MPNST and tumor response to chemotherapy.

Arm I (chemotherapy and local control by radiotherapy and surgery):

• Patients receive doxorubicin hydrochloride and ifosfamide (IA) chemotherapy comprising doxorubicin hydrochloride IV over 15 minutes on Days 1 and 2 and ifosfamide IV over 1 hour on Days 1–5
• Treatment repeats every 21 days for two courses in the absence of unacceptable toxicity
• Patients then receive etoposide and ifosfamide (IE) chemotherapy comprising etoposide IV over 1 hour and ifosfamide IV over 1 hour on Days 1–5
• Treatment repeats every 21 days for two courses in the absence of disease progression or unacceptable toxicity. Patients also receive filgrastim (G-CSF) subcutaneously (SC) after each chemotherapy course beginning on Day 6 or 7 and continuing until blood counts recover or pegfilgrastim SC once on Day 6 or 7
• After recovery from chemotherapy, patients undergo radiotherapy and receive two more courses of IE during radiotherapy followed by two more courses of IA after completion of radiotherapy
• Some patients may then undergo surgery

Arm II (chemotherapy and local control by surgery):

• Patients receive two courses of IA followed by two courses of IE as above. After recovery from chemotherapy, patients undergo surgery
• After recovery from surgery, patients receive two more courses of IA followed by two more courses of IE in the absence of disease progression or unacceptable toxicity

After completion of study treatment, patients are followed periodically for up to 5 years.

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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.
• FAQs about this study - provides information for patients about the trial such as frequency and duration of visits, costs, how to enroll, treatment plan.
• PDQ (Physicians Data Query) - provides additional details about this study for health care providers.

Reviewed: 6/8/09
Updated: 6/1/09