Temozolomide Plus Peripheral Stem Cell Transplantation in Treating Children With Newly Diagnosed Malignant Glioma or Recurrent CNS or Other Solid Tumors

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of temozolomide when given with peripheral stem cell transplantation and to see how well they work in treating children with newly diagnosed malignant glioma or recurrent CNS tumors or other solid tumors.

Detailed Description
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OBJECTIVES: Determine the maximum tolerated dose of temozolomide in children with newly diagnosed malignant glioma or recurrent CNS or other solid tumors. Evaluate the toxicity of this treatment in these patients. Determine the activity of this treatment in these patients. OUTLINE: This is a dose escalation study of temozolomide. Patients receive filgrastim (G-CSF) subcutaneously (SQ) or IV beginning on day -5 and continuing through at least day 3. Peripheral blood stem cells (PBSC) are collected on days 0, 2, and 4. Patients then receive oral temozolomide daily for 5 consecutive days. PBSC collections are reinfused 1 day after the last dose of temozolomide. Patients also receive G-CSF beginning at the time of transplant and continuing until blood counts recover. Treatment continues in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of temozolomide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2 of 6 patients experience dose limiting toxicities. Patients are followed every 3 months for 1-3 years, then annually thereafter. PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study over 12 months.

Official Title
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A Phase I/II Trial of Temodar in Pediatric Patients and Young Adults With High-Risk or Recurrent Solid Tumors

Conditions
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Brain and Central Nervous System Tumors, Childhood Germ Cell Tumor, Head and Neck Cancer, Kidney Cancer, Neuroblastoma, Ovarian Cancer, Sarcoma, Testicular Germ Cell Tumor

Intervention / Treatment
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* Biological: filgrastim
* Drug: temozolomide
* Procedure: peripheral blood stem cell transplantation


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed newly diagnosed malignant glioma or recurrent malignant CNS tumor of any pathology OR Histologically confirmed non-CNS tumor Recurrent soft tissue sarcomas (e.g., rhabdomyosarcoma) Recurrent or resistant neuroblastoma Recurrent Wilm's tumor Recurrent Ewing's sarcoma Recurrent primitive neuroectodermal tumors Recurrent nasopharyngeal carcinoma Recurrent germ cell tumor Expected cure rate less than 10% with standard therapy Measurable and/or active disease History of bone marrow tumor infiltration with or without mass lesions or isolated abnormal CSF cytology as only evidence of recurrent disease allowed if complete response was first achieved with primary conventional therapy PATIENT CHARACTERISTICS: Age: 18 and under Performance status: Karnofsky 70-100% OR Lansky 70-100% Life expectancy: Greater than 8 weeks Hematopoietic: Reasonably cellular bone marrow (greater than 15% cellularity on biopsy) Absolute neutrophil count greater than 1,000/mm^3 Platelet count greater than 75,000/mm^3 Hepatic: Bilirubin less than 2.0 mg/dL SGPT less than 120 U/L Renal: Creatinine less than 1.5 mg/dL Cardiovascular: Systolic fraction or ejection fraction at least 80% predicted for age by echocardiogram Pulmonary: CVC or DLCO at least 60% predicted for age OR clearance from pulmonologist Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception HIV negative No active infection Able to tolerate vigorous hydration schedule PRIOR CONCURRENT THERAPY: Biologic therapy: No concurrent white blood cell transfusion No other concurrent hematopoietic growth factors Chemotherapy: See Disease Characteristics At least 4 weeks since prior chemotherapy No other concurrent cytotoxic drugs (systemic or intrathecal) Endocrine therapy: Concurrent corticosteroids allowed Radiotherapy: See Disease Characteristics At least 1 week since prior radiotherapy Surgery: At least 1 week since prior surgery Other: No other concurrent investigational agents

Ages Eligible for Study
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Maximum Age: 18 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


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: filgrastim|nan|
|Drug: temozolomide|nan|
|Procedure: peripheral blood stem cell transplantation|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response at 12 months |  |  | 
| Disease-free survival at 12 months |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity by NCI Common Toxicity Criteria v. 3.0 at 12 months |  |  | 
| Engraftment related to autologous marrow or peripheral blood stem cell transplantation at 12 months |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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childhood low-grade cerebral astrocytoma, recurrent childhood rhabdomyosarcoma, childhood craniopharyngioma, disseminated neuroblastoma, stage 4S neuroblastoma, recurrent neuroblastoma, stage IV Wilms tumor, stage V Wilms tumor, recurrent Wilms tumor and other childhood kidney tumors, childhood central nervous system germ cell tumor, stage III malignant testicular germ cell tumor, recurrent malignant testicular germ cell tumor, stage IV nasopharyngeal cancer, recurrent nasopharyngeal cancer, childhood germ cell tumor, metastatic childhood soft tissue sarcoma, recurrent childhood soft tissue sarcoma, stage IV ovarian germ cell tumor, recurrent ovarian germ cell tumor, childhood high-grade cerebral astrocytoma, childhood oligodendroglioma, childhood choroid plexus tumor, untreated childhood brain stem glioma, recurrent childhood brain stem glioma, untreated childhood supratentorial primitive neuroectodermal tumor, recurrent childhood supratentorial primitive neuroectodermal tumor, untreated childhood cerebellar astrocytoma, recurrent childhood cerebellar astrocytoma, recurrent childhood cerebral astrocytoma, untreated childhood medulloblastoma, recurrent childhood medulloblastoma, untreated childhood visual pathway and hypothalamic glioma, recurrent childhood visual pathway and hypothalamic glioma, previously treated childhood rhabdomyosarcoma, metastatic Ewing sarcoma/peripheral primitive neuroectodermal tumor, recurrent Ewing sarcoma/peripheral primitive neuroectodermal tumor, newly diagnosed childhood ependymoma, recurrent childhood ependymoma