Chemotherapy and Radiation Therapy After Surgery in Treating Children With Newly Diagnosed Astrocytoma, Glioblastoma Multiforme, Gliosarcoma, or Diffuse Intrinsic Pontine Glioma

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. Radiation therapy uses high-energy x-rays to damage tumor cells. Giving chemotherapy together with radiation therapy may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving chemotherapy together with radiation therapy after surgery followed by chemotherapy alone works in children with newly diagnosed astrocytoma, glioblastoma multiforme, gliosarcoma, or diffuse intrinsic pontine glioma.

Detailed Description
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OBJECTIVES: Compare the event-free survival of patients with newly diagnosed anaplastic astrocytoma, glioblastoma multiforme, gliosarcoma, or diffuse intrinsic pontine glioma (DIPG) treated with adjuvant temozolomide administered concurrently with postoperative radiotherapy and then alone as maintenance therapy vs historical control cohorts treated in prior Pediatric Oncology Group and Children's Cancer Group studies. Determine the toxicity of this regimen in these patients. Determine the efficacy of this regimen in patients with DIPG. Determine the toxicity of this regimen in patients with DIPG. OUTLINE: This is a multicenter study. Adjuvant chemoradiotherapy: Beginning within 6 weeks after surgical resection or diagnosis*, patients without gross residual disease undergo cranial irradiation 5 days a week for 6 weeks. Beginning within 6 weeks after surgical resection, patients with gross residual disease undergo radiotherapy as above followed by boost radiotherapy for 1 week. All patients receive oral temozolomide once daily beginning within 5 days after initiation of radiotherapy and continuing for a total of 6 weeks in the absence of disease progression or unacceptable toxicity. Adjuvant maintenance therapy: Beginning 4 weeks after completion of adjuvant chemoradiotherapy, patients receive oral temozolomide on days 1-5. Treatment repeats every 28 days for a total of 10 courses in the absence of disease progression or unacceptable toxicity. NOTE: *For patients with diffuse intrinsic pontine glioma only Patients are followed every 3-6 months for 4 years and then annually thereafter. PROJECTED ACCRUAL: A total of 50-60 patients will be accrued for this study within 12-14 months.

Official Title
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A Phase II Study of Temozolomide in the Treatment of Children With High Grade Glioma

Conditions
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Brain and Central Nervous System Tumors

Intervention / Treatment
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* Drug: temozolomide
* Procedure: adjuvant therapy
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed newly diagnosed CNS tumor of the following types: High grade glioma (HGG) of one of the following histologies: Anaplastic astrocytoma (grade III) Glioblastoma multiforme (grade IV) Gliosarcoma Primary spinal cord malignant glioma Diffuse intrinsic pontine glioma (DIPG) Diagnosed by gadolinium-enhanced MRI At least 2/3 of tumor situated in the pons AND tumor clearly originated in the pons No diffuse leptomeningeal disease No tumors with features not typical of diffuse intrinsic brainstem glioma, including any of the following: Dorsally exophytic brainstem glioma Cervico-medullary junction tumor Focal low-grade glioma of the midbrain or brainstem No diffuse brainstem enlargement due to neurofibromatosis No primary brain stem malignant glioma No M+ disease (CSF positive for tumor or metastatic disease) Must begin study radiotherapy within 6 weeks after surgical resection (for HGG patients) or diagnosis (for DIPG patients) PATIENT CHARACTERISTICS: Age: 3 to 21 Performance status: Karnofsky 50-100% OR Lansky 50-100% Life expectancy: At least 2 months Hematopoietic: Absolute neutrophil count at least 1,000/mm^3 Platelet count at least 100,000/mm^3* Hemoglobin at least 10.0 g/dL* NOTE: *Transfusion independent Hepatic: Bilirubin no greater than 1.5 times upper limit of normal (ULN) SGOT or SGPT less than 2.5 times ULN Renal: Creatinine no greater than 1.5 times ULN Other: No other concurrent malignancy Concurrent seizure disorder allowed if well controlled on anticonvulsants Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 2 months after completion of study treatment PRIOR CONCURRENT THERAPY: Biologic: No concurrent routine cytokine support Chemotherapy: Not specified Endocrine therapy: No concurrent corticosteroids except for increased intracranial pressure in patients with CNS tumors Radiotherapy: See Disease Characteristics Surgery: See Disease Characteristics Other: No prior therapy for HGG or DIPG

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 21 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: Chemoradiotherapy<br> | Drug: temozolomide<br> <br> Procedure: adjuvant therapy<br> <br> Radiation: radiation therapy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improved outcome |  |  | 
| Toxicity as assessed by NCI CTCAE v. 2.0 |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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childhood brain stem glioma, childhood high-grade cerebral astrocytoma, childhood spinal cord neoplasm, untreated childhood brain stem glioma