Antineoplaston Therapy in Treating Children With Recurrent or Refractory High-Grade Glioma

OBJECTIVES:

- To determine the efficacy of Antineoplaston therapy in children with
recurrent/progressive high grade gliomas, as measured by an objective response to
therapy (complete response, partial response or stable disease).

- To determine the safety and tolerance of Antineoplaston therapy in children with
recurrent/progressive high grade gliomas.

OVERVIEW: This is a single arm, open-label study in which children with recurrent/progressive
high grade gliomas receive gradually escalating doses of intravenous Antineoplaston therapy
(Atengenal + Astugenal) until the maximum tolerated dose is reached. Treatment continues for
at least 12 months in the absence of disease progression or unacceptable toxicity. After 12
months, patients with a complete or partial response or with stable disease may continue
treatment.

To determine objective response, tumor size is measured utilizing MRI scans, which are
performed every 8 weeks for the first two years, every 3 months for the third and fourth
years, every 6 months for the 5th and sixth years, and annually thereafter.

PROJECTED ACCRUAL: A total of 20-40 patients will be accrued for this study.

Inclusion Criteria:

- Histologically confirmed high-grade glioma (glioblastoma multiforme or anaplastic
astrocytoma) that is recurrent or progressive or with residual tumor after standard
therapy, including radiotherapy

- Measurable tumor by MRI scan performed within two weeks prior to study entry

- Male or female patients

- Children 6 months to 17 years

- Performance status: Karnofsky 60-100%

- Life expectancy of at least 2 months

- WBC greater than 1,500/mm^3

- Platelet count greater than 50,000/mm^3

- No evidence of hepatic or renal insufficiency and a total bilirubin and serum
creatinine no greater than 2.5 mg/dL and SGOT/SGPT no greater than 5 times upper limit
of normal

- Must have recovered from adverse effect of previous therapy

- At least 8 weeks elapsed since last dose of radiation

- At least 4 weeks elapsed since last dose of chemotherapy (6 weeks for nitrosoureas)

- Corticosteroids permitted using the smallest dose that is compatible with preservation
of optimal neurologic function

- Acceptable methods of birth control (in females of child-bearing potential or in
sexually active males)during and up to four weeks following completion of study

Exclusion Criteria:

- Prior A10 and AS2-1 treatment

- Severe heart disease

- Uncontrolled hypertension

- Lung disease

- Hepatic failure

- Serious active infections, fever or other serious concurrent disease that would
interfere with the evaluation of the treatment drug.

- Pregnant or nursing

- Serious concurrent disease

- Concurrent antineoplastic or immunomodulatory agents