A phase II study of Antineoplastons A10 And AS2-1 Private In Children With Primary Malignant Brain Tumors

Description

To demonstrate the antitumor activity of Antineoplaston A10 and AS2-1 in the treatment of children with primary malignant brain tumors by determining the proportion of patients who experience an objective tumor response. To evaluate the adverse effects and tolerance of Antineoplaston A10 and AS2-1 in these patients.

Inclusion Criteria

Patients must be at least 6 months of age or less than 18 years of age. Patients must have a histologically confirmed incurable primary malignant brain tumor than has progressed, recurred, or persisted ( with radiological findings that are highly suggestive of residual tumor, in the opinion of the consulting radiologist) following completion of initial therapy, including radiation therapy. At least eight weeks must have elapsed since the last dose of radiation therapy and at least four weeks must have elapsed since the last dose of chemotherapy ( six weeks for nitrosoureas ) or immunotherapy. However, patients with clear evidence of disease progression during the initial therapy may be enrolled less than 8 weeks following the last dose of radiation therapy, less than 4 weeks after surgery or the last dose of chemotherapy, if the investigator has determined that it is safe to administer antineoplastons to such patients.
Since the full effectiveness of initial therapy ( including radiation therapy ) may not be seen until a few is months after the initial therapy is completed , it is very difficult to analyze the effectiveness of initial therapy before the patient has completed treatment and follow-up. Because of this treatment decisions are usually not made on the base of radiological studies performed earlier than four weeks following completion of radiation therapy. However, patients with clear evidence of disease progression during the initial therapy may be enrolled less than (8) eight weeks following the last dose of radiation therapy, less than 4 weeks after surgery or the last dose of chemotherapy, if the investigator has determined that it is safe to administer antineoplastons to such patients.
Patients who have recurrent or progressive disease following standard therapy, including radiation therapy, are eligible.
Patients who did not receive standard therapy are eligible.
Patients must have evidence of brain tumor by gadolinium- enhanced MRI, or if MRI is contraindicated, contrast-enhanced CT scan performed within two weeks prior to entry. There will be no exclusion based on tumor size, multifocality, or leptomeningeal or systemic metastases.
Patients must have a performance status of 60% to 100% on the Karnofsky Performance Scale (Appendix C). Patients must have no evidence of hepatic insufficiency, total bilirubin below 0.5 mg/dL, and SGOT and SGPT not higher than five times the upper limit of normal.
Patients must have a relatively normal hematopoietic and hepatic function, WBC > 1500/mm3, and platelets > 50,000/mm3.
Patients may be male or female. If female is of childbearing age, the patient must not be pregnant or breast-feeding an infant, and either incapable of becoming pregnant or currently using contraceptives. Acceptable methods include the birth control pill, use of a diaphragm, intrauterine device, or condom by the patient's sexual partner. If the male is of a sexually active age, the patient should use appropriate contraception, such as condoms during the study and at least 4 weeks following completion of the study. Patients must have recovered from the toxicity of prior therapy.
Patients should be outpatients, but must have a life expectancy of at least two months with the feasibility of doing a complete follow-up.
The use of corticosteroids is permitted to reduce symptoms and signs attributed to cerebral edema. It is recommended that the smallest dose be used which is compatible with the preservation of optimal neurologic function. Corticosteroids should be carefully monitored and recorded.
Patients must recover from the adverse effect of previous therapy. At least eight weeks must have relapsed since the last dose of radiation therapy and at least four weeks must have relapsed since the last dose of chemotherapy (six weeks for nitrosoureas) or immunotherapy.

EXCLUSION CRITERIA

• Patients should not have serious active infections, fever, or other serious concomitant disease that would interfere with the evaluation of treatment drug (e.g., severe heart or lung disease, or hepatic failure).
• Patients with hypertension are excluded unless the blood pressure is adequately controlled.
• Patients who have had prior Antineoplaston treatment should be excluded from this protocol.
• Patients with brain stem location of the tumor are excluded.

Details