Phase I Study of Safety and Tolerability of Acetazolamide With Temozolomide

Inclusion Criteria:

- Histologically proven, newly diagnosed WHO grade III or IV astrocytoma that has a
methylated MGMT promoter as assessed by the standardized institutional analysis.

- Patients are eligible if they had a prior low grade astrocytoma and there is
subsequent histological evidence of a diagnosis of grade III or IV tumor.

- Patients must be receiving TMZ as part of their standard adjuvant treatment regimen
following treatment with TMZ and Radiation.

- Patients must have a Karnofsky performance ≥ 60%.

- Normal organ function as follows:

- Absolute Neutrophil Count (ANC) ≥ 1.0 x 10^9/ L

- Platelets ≥ 100 x 10^9 / L

- Hemoglobin ≥ 8.0 g / dL

- Age 18 years or older.

- Kidney function (creatinine level within normal institutional limit, or creatinine
clearance ≥ 60 mL/min/1.73 m2 for patients with creatinine level above institutional
normal).

- Liver function (AST/ALT <2.5 X institutional upper limit of normal (ULN), Total
bilirubin ≤ 1.5 times ULN, INR within 1.5 times ULN (or if receiving anticoagulant
therapy an INR of ≤ 3.0 is allowed with concomitant increase in PT or an aPTT ≤ 2.5 ×
control).

- Women able to become pregnant must have a negative pregnancy test within 30 days of
registration.

- Patients must have the ability to understand and the willingness to sign a written
informed consent document.

Exclusion Criteria:

- Prior invasive malignancy that is not low-grade glioma (except non-melanomatous skin
cancer or carcinoma in situ of the cervix) unless the patient has been disease free
and off therapy for that disease for a minimum of 3 years.

- Active systemic infection requiring treatment, including any HIV infection or
toxoplasmosis.

- Other severe acute or chronic medical or psychiatric condition, or laboratory
abnormality that may increase the risk associated with study participation or study
drug administration.

- Systemic corticosteroid therapy, >8 mg of dexamethasone daily (or equivalent) at study
enrollment.

- Pregnant women are excluded from this study, where pregnancy is confirmed by a
positive serum beta-hCG laboratory test. Breast-feeding should be discontinued.

- Hypersensitivity to acetazolamide or sulfonamides.