Combination Chemotherapy With or Without Sodium Thiosulfate in Preventing Low Platelet Count While Treating Patients With Malignant Brain Tumors

PRIMARY OBJECTIVES:

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