• Proportion of confirmed tumor response (complete or partial response) [ Designated as safety issue: No ]
  

• Toxicity as measured by NCI CTCAE v3.0 [ Designated as safety issue: Yes ]
  
• Survival time as measured by Kaplan-Meier [ Designated as safety issue: No ]
  
• Time to disease progression as measured by Kaplan-Meier [ Designated as safety issue: No ]
  
• Duration of response as measured by Kaplan-Meier [ Designated as safety issue: No ]
  
• Time to treatment failure due to progression, toxicity, or refusal as measured by Kaplan-Meier [ Designated as safety issue: Yes ]
  
• Relationship between 3-D MRI measurements and 2-D MRI measurements as measured by linear regression, Pearson's correlation coefficient, and Bland-Altman approach [ Designated as safety issue: No ]
  
• Tumor objective response determined by 3D MRI and conventional 2-D MRI as measured by Kappa statistic [ Designated as safety issue: No ]
  
• Quality of life (QOL) as measured by the Brief Pain Inventory, Brief Fatigue Inventory, and North Central Cancer Treatment Group Supplemental QOL Questionnaire [ Designated as safety issue: No ]
  
• Biological changes in pre- and post-treatment human and/or mouse xenograft tumor tissue as measured by immunostaining for CD34, CD31, and vascular endothelial growth factor (VEGF) [ Designated as safety issue: No ]
  
• Correlation of biological changes in pre- and post-treatment tumor tissue with tumor objective response, imaging measures (tumor volume, delayed contrast-enhanced MRI [DCE-MRI]), and QOL [ Designated as safety issue: No ]
  
• Levels of VEGF and soluble FLT(sFLT) measured as surrogate markers of angiogenesis [ Designated as safety issue: No ]
  
• Correlation of serum vs tumor VEGF [ Designated as safety issue: No ]
  
• Effect of AZD2171 on VEGF serum levels as measured at baseline and every 4 weeks during treatment [ Designated as safety issue: No ]
  
• Correlation of VEGF serum levels with response, time to progression, and survival [ Designated as safety issue: No ]
  
• Correlation of circulating endothelial cells with clinical response and with other angiogenic biomarkers [ Designated as safety issue: No ]
  
• Pharmacogenetics analyses (variation in kdr/flk-1 and other genes) at 6 months after completion of study treatment [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• Assess the efficacy of AZD2171, in terms of volume change in target tumors by 3-dimensional (3D) MRI in patients with neurofibromatosis type 1 and extensive plexiform and/or paraspinal neurofibromas.
• Describe and define the toxicities of AZD2171 in these patients.

Secondary

• Assess the value of 3D MRI data analysis in evaluating plexiform or paraspinal neurofibromas compared to conventional 2-dimensional MRI data analysis.
• Assess the value of delayed contrast-enhanced MR imaging in determining changes in vascularity of neurofibromas before and during treatment.
• Assess the quality of life of patients treated with AZD2171.
• Evaluate the effect of AZD2171 on biological changes of human neurofibroma by comparing pre- and post-treatment specimens from patients involved in this trial or, alternatively, by evaluating the effect of AZD2171 on human tumor grafts in experimental animals.
• Evaluate relevant pharmacodynamic markers (circulating endothelial cells and vascular endothelial growth factor-2 [VEGF2] levels) and pharmacogenetics analyses (variation in kdr/flk-1 and other genes) in response to AZD2171.

OUTLINE: This is a multicenter study. Patients are stratified according to tumor location (peripheral vs paraspinal plexiform neurofibroma).

Patients receive oral AZD2171 once daily on days 1-28. Treatment repeats every 28 days for 26 courses in the absence of disease progression or unacceptable toxicity. Patients with responding or stable disease may continue treatment beyond 26 courses in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, after course 1, after every 3 courses, and then at completion of study treatment.

PROJECTED ACCRUAL: A total of 65 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Diagnosis* of neurofibromatosis type 1 (NF1) and extensive plexiform and/or paraspinal neurofibromas producing pain (not controlled by use of over-the-counter medications), progressive neurologic deficit, or significant neurologic consequences with continuous tumor growth

  • Extensive paraspinal neurofibroma defined as a neurofibroma that involves multiple neural roots at ≥ 3 spinal levels with connection between the levels or extending laterally along the nerves

    • Symptomatic neurofibromas at < 3 spinal levels, but surgical treatment is not possible, allowed NOTE: * Histologic confirmation of tumor not required in the presence of consistent clinical and radiographic findings

• Meets ≥ 2 diagnostic criteria for NF1, including the following:

  • Six or more café-au-lait spots (≥ 1.5 cm in postpubertal patients)
  • Freckling in the axilla or groin
  • Optic glioma
  • Two or more Lisch nodules
  • Distinctive bony lesion (dysplasia of the sphenoid bone or dysplasia or thinning of long-bone cortex)
  • First-degree relative with NF1
• Patients with documented mutation in neurofibromin gene with only symptomatic plexiform and/or paraspinal neurofibroma who do not fulfill the above clinical criteria are eligible

• Measurable disease, defined as ≥ 1 lesion whose longest diameter can be accurately measured as 8.0 cm^3 with 3-dimensional (3D) MRI

  • Skin lesions are considered measurable (e.g., plexiform neurofibromas), but MRI imaging still required for 3D measurement
• Patients with symptomatic neurofibroma, in whom surgery is not feasible, who refuse surgery or are not good surgical candidates due to high risk of damage to vital structures or spinal cord injury are eligible
• No evidence of progressive optic glioma, malignant glioma, malignant peripheral nerve sheath tumor, or other cancer requiring treatment with chemotherapy or radiotherapy

PATIENT CHARACTERISTICS:

• ECOG performance status 0-3
• WBC ≥ 3,000/mm^3
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 8.0 g/dL
• Bilirubin normal
• Alkaline phosphatase normal
• AST and ALT ≤ 2.5 times upper limit of normal
• Thyroid-stimulating hormone and free thyroxin normal
• Creatinine normal OR creatinine clearance ≥ 60 mL/min
• Ejection fraction ≥ 50% by echocardiogram
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

• No other uncontrolled, serious medical condition that would preclude study participation, including any of the following:

  • Cardiac arrhythmia
  • Diabetes
  • Serious infection
  • Significant cardiac, pulmonary, hepatic, or other organ dysfunction
• No psychiatric illness or social situation that would preclude study compliance
• No history of allergic reactions attributed to compounds of similar chemical or biologic composition to AZD2171

• No New York Heart Association class III or IV disease

  • Class II disease controlled with treatment and increased monitoring allowed
• No systolic blood pressure (BP) > 130 mm Hg and diastolic BP > 90 mm Hg
• No history of familial long QT syndrome
• Mean QTc ≤ 470 msec (with Bazett's correction) by EKG
• QTc prolongation ≤ 500 msec
• No other significant ECG abnormality within the past 14 days

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• More than 30 days since prior investigational agents
• More than 4 weeks since prior radiotherapy, chemotherapy, hormonal therapy directed at the tumor, immunotherapy, biologic therapy (e.g., interferon), or major surgery
• No concurrent medication that may markedly affect renal function (e.g., vancomycin, amphotericin, or pentamidine)
• No concurrent CYP interactive medications
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No concurrent enzyme-inducing anticonvulsants (e.g., phenytoin, carbamazepine, or phenobarbital)
• No concurrent use of drugs or biologics with proarrhythmic potential