Study of Acetazolamide With Temozolomide in Adults With Newly Diagnosed or Recurrent Malignant Glioma

This is a Phase I study that examines the rate of dose limiting side effects in patients with malignant astrocytoma treated with combination acetazolamide (ACZ) and temozolomide (TMZ). Eligible patients must have histologically proven newly diagnosed, O6-methylguanine-DNA methyltransferase (MGMT) methylated WHO grade III or IV astrocytoma and be planning to undergo treatment with standard adjuvant TMZ (after completing treatment with TMZ and ionizing radiation (IR)). During this study, patients will receive daily oral ACZ with TMZ. During each cycle, ACZ will be started on the day of TMZ initiation and continued for a total of 21 days.

Inclusion Criteria: * Histologically proven, newly diagnosed IDH wildtype glioblastoma (GBM) 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.