Clinical Trial Finder

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.

Arms

Experimental: Acetazolamide with Temozolomide

Subjects will receive daily ACZ together with TMZ in 28 day cycles for up to 6 cycles if they do not experience either disease worsening or unacceptable side effects.

Interventions

Drug: - Acetazolamide

ACZ will be given at an initial dose of 250 mg twice a day (BID) and then escalated to 500 mg BID after 1 week. ACZ will be given on days 1-21 of each cycle.

Drug: - Temozolomide

For cycle 1 of the maintenance phase, TMZ will administered at 150 mg/m2 on days 1- 5 followed by 23 days with no drug. For cycles 2- 6, TMZ can be increased to 200 mg/m2 at the discretion of the treating investigator.