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

Phase II Study of Antineoplastons A10 and AS2-1 in Children With High Grade Glioma

RATIONALE: Current therapies for children with recurrent/progressive high grade gliomas provide very limited benefit to the patient. The anti-cancer properties of Antineoplaston therapy suggest that it may prove beneficial in the treatment of children with recurrent/progressive high grade gliomas.

PURPOSE: This study is being performed to determine the effects (good and bad) that Antineoplaston therapy has on children (> 6 months of age) with recurrent/progressive high grade gliomas.

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