OBJECTIVES:

• Determine the response rate of patients with relapsed or refractory pediatric solid tumors treated with imatinib mesylate.
• Determine the toxicity of this drug in these patients.
• Determine the time to progression in patients treated with this drug.
• Determine the pharmacokinetics of this drug in these patients.
• Correlate response with c-kit and platelet-derived growth factor receptor expression in patients treated with this drug.

OUTLINE: This is a multicenter study. Patients are stratified according to disease (Ewing's sarcoma/primitive neuroectodermal tumor vs osteosarcoma vs neuroblastoma vs other).

Patients receive oral imatinib mesylate once or twice daily on days 1-28. Courses repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A maximum of 100 patients (10-25 per stratum) will be accrued for this study within 12 to 18 months.

DISEASE CHARACTERISTICS:

• Histologically confirmed solid tumors including the following:

  • Ewing's sarcoma
  • Bone or soft tissue primitive neuroectodermal tumor
  • Osteosarcoma
  • Neuroblastoma
  • Desmoplastic small round cell tumor
  • Synovial cell sarcoma
  • Gastrointestinal stromal tumor (GIST)

• Metastatic pulmonary disease eligible

  • No pleural effusion of any size or definite radiologic evidence of pleural-based disease

• Recurrent or refractory to conventional therapy

  • GIST eligible at initial presentation
• Tumor tissue blocks must be available

• At least 1 measurable lesion

  • At least 20 mm by conventional techniques OR
  • At least 10 mm by spiral CT scan
  • Lesions assessable only by radionuclide scan are not considered measurable

PATIENT CHARACTERISTICS:

Age:

• 30 and under

Performance status:

• Lansky 50-100% (≤ 10 years of age)
• Karnofsky 50-100% (> 10 years of age)

Life expectancy:

• At least 2 months

Hematopoietic:

• Absolute neutrophil count ≥ 1,000/mm^3*
• Platelet count ≥ 75,000/mm^3* (transfusion independent)
• Hemoglobin ≥ 8.0 g/dL* (RBC transfusions allowed) NOTE: *Unless due to bone marrow involvement

Hepatic:

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• ALT ≤ 2.5 times ULN
• INR < 1.5
• PTT ≤ ULN
• Fibrinogen ≥ lower limit of normal

Renal:

• Creatinine normal for age OR
• Glomerular filtration rate ≥ 70 mL/min

Other:

• No uncontrolled infection
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective barrier contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• At least 1 week since prior biologic therapy or immunotherapy and recovered
• At least 1 week since prior growth factors
• No concurrent immunomodulating agents

Chemotherapy:

• At least 2 weeks since prior myelosuppressive chemotherapy (4 weeks for nitrosoureas) and recovered
• No concurrent chemotherapy

Endocrine therapy:

• No concurrent steroids

Radiotherapy:

• Recovered from prior radiotherapy
• At least 2 weeks since prior local palliative radiotherapy (small port)
• At least 3 months since prior craniospinal radiotherapy or radiotherapy to 50% or more of pelvis
• At least 6 weeks since other prior substantial bone marrow radiation
• No concurrent radiotherapy during first course of treatment
• Concurrent palliative radiotherapy to local painful lesions allowed after first course of treatment provided there is no evidence of disease progression and at least 1 measurable lesion remains outside radiation port

Surgery:

• Not specified

Other:

• No concurrent therapeutic doses of warfarin
• No concurrent anticonvulsants that induce the cytochrome p450 enzyme system (e.g., phenytoin, carbamazepine, and phenobarbital)
• Concurrent benzodiazepines and gabapentin allowed
• Concurrent low-molecular weight heparin allowed