Inclusion Criteria:

- Evidence of recurrent disease.

- All patients will have received previous conventional radiotherapy at least 3 weeks
prior to enrollment. Histologic verification of malignant glioma is required. If the
initial primary brain tumor was histologically malignant glioma and subsequent
contrast enhanced MRI imaging shows tumor consistent with recurrence, additional
biopsy or surgery is not required. However, if a low-grade neoplasm was the initial
histologic diagnosis, tissue confirmation of malignant glioma is required at the time
of recurrence.

- Age: Patients must be >18 years of age

- Patients must have a Karnofsky >60%, and/or ECOG performance status <2

- Patients must have an estimated life expectancy of greater than 8 weeks.

- Patients must have normal organ and marrow functions as defined below:

- Leukocytes >3,000/¼l

- Absolute neutrophil count >1,500/¼l

- Hemoglobin > 10 gm/dl

- Platelets >100,000/¼l (transfusion independent)

- Total bilirubin within normal institutional limits

- AST (SGOT)/ALT (SGPT) <1.5 X institutional upper limit of normal

- Creatinine within normal institutional limits OR

- Creatinine clearance >60mL/min/1.73 m2 for patients with creatinine levels above
institutional normal

- Serum potassium* e 4.0mEq/L

- Serum magnesium* e 1.8mEq/L

- Serum calcium* within the institutional normal range (should be corrected if low
normal)

- Electrocardiogram Normal

- electrocardiogram with a rate corrected QT interval (QTc) <500 msec

*Oral or intravenous supplementation may be used to normalize serum electrolytes

- Phase I ATO Stereotactic Radiotherapy for Recurrent Malignant Glioma 16 of 44

- Informed consent All patients or their legal guardians must sign a document of
informed consent indicating their understanding of the investigational nature of this
study and the risks involved prior to any protocol related are performed (which does
not include imaging and laboratory studies that help to establish eligibility).

Exclusion Criteria:- Patients who have had chemotherapy or conventional radiotherapy
within 3 weeks of enrollment.

- Patients who have received prior radiosurgery or stereotactic radiotherapy within
10mm of the current target tumor.

- Patients may not be receiving any other investigational agents.

- Patients who cannot undergo MRI or CT are not eligible as MRI will be used to confirm
the diagnosis and CT will be used for treatment planning.

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to arsenic trioxide or other agents used in study.

- Patients who are taking substances known to prolong the QT interval, see Appendix B.
If the QT prolonging drug is discontinued and switched to an alternative agent, the
patients will be allowed to enroll into this protocol as long the agent has been
discontinued for a period of at least 2 weeks.

- Patients currently taking Amphotericin B or related antifungal agents will be
excluded due to potential for increased renal electrolyte wasting during arsenic
trioxide therapy.

- Patients with known second-degree heart block or other cardiac dysfunction. New York
Heart Association Class II or greater (see Appendix E)

- Uncontrolled intercurrent illnesses including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, or
psychiatric illness/social situations that would limit compliance with study
requirements. Phase I ATO Stereotactic Radiotherapy for Recurrent Malignant Glioma 17
of 44

- Patients must not be pregnant or breast-feeding. All patients with the potential for
pregnancy should be counseled and requested to follow acceptable birth control
methods (hormonal or barrier method of birth control; abstinence) prior to study
entry and for the duration of study participation. Patients who are pregnant or
breast-feeding will be excluded because no information on this agent exists with
regard to safety of arsenic trioxide for a fetus or breast-feeding infant. Should a
woman become pregnant or suspect she is pregnant while participating in this study,
she should inform her treating physician immediately.