This randomized phase II trial studies how well giving combination chemotherapy with or without sodium thiosulfate works in preventing low platelet count while treating patients with malignant brain tumors. Drugs used in chemotherapy, such as carboplatin, cyclophosphamide, and etoposide phosphate, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Sodium thiosulfate may prevent low platelet counts in patients receiving chemotherapy. It is not yet known whether combination chemotherapy is more effective with or without sodium thiosulfate in preventing low platelet count during treatment for brain tumors.

PRIMARY OBJECTIVE:

I. Determine the effect of delayed administration of sodium thiosulfate on the rates of platelet toxicity (i.e. platelet count less than 20,000), in subjects with high-grade glioma undergoing treatment with carboplatin, cyclophosphamide and etoposide/etoposide phosphate.

SECONDARY OBJECTIVES:

I. Assess tumor response in subjects with high-grade glioma undergoing treatment with carboplatin, cyclophosphamide and etoposide/etoposide phosphate, with or without delayed sodium thiosulfate.

II. Assess the effect of delayed administration of sodium thiosulfate on granulocyte and erythrocyte counts, in subjects undergoing treatment with carboplatin, cyclophosphamide and etoposide/etoposide phosphate.

III. Assess hearing changes, if any, at the higher frequencies in the standard testing range (4000 and 8000 Hertz [Hz]), and at higher frequencies above standard testing (9000 to 16000 Hz).

IV. Assess quality of life in subjects undergoing treatment with carboplatin, cyclophosphamide and etoposide phosphate.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive cyclophosphamide intravenously (IV), etoposide phosphate IV, and carboplatin intra-arterially (IA) over 10 minutes on day 1.

ARM II: Patients receive cyclophosphamide IV, etoposide phosphate IV, and carboplatin IA as in Arm I. Patients also receive sodium thiosulfate IV over 15 minutes 4 and 8 hours after carboplatin.

In both arms, treatment repeats every 4 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.

Inclusion Criteria:

• Subjects with histologically confirmed high-grade glioma are eligible; diagnosis of high-grade glioma will be made on the basis of needle biopsy, open biopsy, or surgical resection
• Subjects may have had prior focal or systemic radiation or chemotherapy; at least 14 days must have elapsed since radiation treatment and 28 days since prior chemotherapy
• Performance status (Eastern Cooperative Oncology Group [ECOG]) must be less than or equal to 2 (Karnofsky greater than or equal to 50)
• White blood cell count >= 2.5 x 10^3/mm^3
• Absolute granulocyte count >= 1.2 x 10^3/mm^3
• Platelets >= 100 x 10^3/mm^3
• Creatinine < 1.8
• Bilirubin < 2.0
• Baseline aspartate aminotransferase (AST)/alanine aminotransferase (ALT) serum glutamic oxaloacetic transaminase (SGOT)/serum glutamate pyruvate transaminase (SGPT) must be < 2.5 x institutional upper limits of normal
• Subject (or legal guardian) must sign a written informed consent in accordance with institutional guidelines
• Sexually active women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; or abstinence) prior to study treatment and for the duration of study treatment; should a female become pregnant or suspect she is pregnant while participating in this study, she should inform the investigator

Exclusion Criteria:

• Subjects with rapidly progressing central nervous system (CNS) disease with associated neurological deterioration
• Subjects with uncontrolled (over the last 30 days) clinically significant confounding medical conditions such as congestive heart failure
• Subjects who are pregnant, have a positive serum human chorionic gonadotropin (hCG) or are lactating
• Subjects who have contraindications to carboplatin, cyclophosphamide, etoposide phosphate, or sodium thiosulfate