Imatinib Mesylate in Treating Patients With Relapsed or Refractory Solid Tumors of Childhood

Study Overview
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Brief Summary
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Phase II trial to study the effectiveness of imatinib mesylate in treating patients who have relapsed or refractory solid tumors of childhood. Imatinib mesylate may stop the growth of tumor cells by blocking the enzymes necessary for their growth.

Detailed Description
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OBJECTIVES: I. Determine the response rate of patients with relapsed or refractory pediatric solid tumors treated with imatinib mesylate. II. Determine the toxicity of this drug in these patients. III. Determine the time to progression in patients treated with this drug. IV. Determine the pharmacokinetics of this drug in these patients. V. 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.

Official Title
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A Phase II Study of Gleevec (Imatinib Mesylate, NSC 716051 Formerly STI571) in Children With Refractory or Relapsed Solid Tumors

Conditions
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Childhood Desmoplastic Small Round Cell Tumor, Childhood Synovial Sarcoma, Gastrointestinal Stromal Tumor, Lung Metastases, Recurrent Childhood Soft Tissue Sarcoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Recurrent Neuroblastoma, Recurrent Osteosarcoma

Intervention / Treatment
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* Drug: imatinib mesylate
* Other: laboratory biomarker analysis
* Other: pharmacological study


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 At least 10 mm by spiral CT scan Lesions assessable only by radionuclide scan are not considered measurable Performance status - Lansky 50-100% (≤ 10 years of age) Performance status - Karnofsky 50-100% (> 10 years of age) At least 2 months Absolute neutrophil count ≥ 1,000/mm^3* Platelet count ≥ 75,000/mm^3* (transfusion independent) Hemoglobin ≥ 8.0 g/dL* (RBC transfusions allowed) Bilirubin ≤ 1.5 times upper limit of normal (ULN) ALT ≤ 2.5 times ULN INR < 1.5 PTT ≤ ULN Fibrinogen ≥ lower limit of normal Creatinine normal for age Glomerular filtration rate ≥ 70 mL/min No uncontrolled infection Not pregnant or nursing Negative pregnancy test Fertile patients must use effective barrier contraception At least 1 week since prior biologic therapy or immunotherapy and recovered At least 1 week since prior growth factors No concurrent immunomodulating agents At least 2 weeks since prior myelosuppressive chemotherapy (4 weeks for nitrosoureas) and recovered No concurrent chemotherapy No concurrent steroids 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 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

Ages Eligible for Study
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Maximum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (imatinib mesylate)<br>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. | Drug: imatinib mesylate<br>* Given orally<br>* Other names: Glivec;Other: laboratory biomarker analysis<br>* Correlative studies<br>Other: pharmacological study<br>* Correlative studies<br>* Other names: pharmacological studies;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate, determined using the RECIST criteria | 95% confidence interval will be computed. | Up to 2 years | 
| Toxicity reported using the CTC version 2.0 |  | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to disease progression | Calculated by the method of Kaplan and Meier. | Up to 2 years |