Methimazole in Patients With Progressive Glioblastoma

Inclusion Criteria

• •Subjects must have histologically or cytologically confirmed WHO grade 4 glioma (including tumors with molecularly defined grade 4 astrocytoma) for which a clinically indicated tumor resection is planned.
• •Subjects must not have received methimazole for this disease.
• •Age is greater than or equal to 18 years of age
• •Performance status: Karnofsky Performance status ≥ 70%
• •Subjects must have adequate organ function and laboratory parameters within 21 days of study entry as defined below: Hemoglobin ≥ 8 g/dl, Absolute neutrophil count ≥ 1,200/mcL, Platelet count ≥ 75,000/mcL, Total bilirubin \< 1.5 x institutional upper limit of normal (ULN), AST (SGOT) ≤ 3 X institutional ULN, ALT (SGPT) ≤ 3 X institutional ULN, Calculated creatinine clearance \> 50 mL/min, Prothrombin time/international normalized ratio (PT/INR) \<1.4 for patients not on warfarin, Patients on full-dose anticoagulants (e.g., warfarin or LMW heparin) must meet both of the following criteria: No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices), In-range INR (between 2 and 3) on a stable dose of oral anticoagulant or on a stable dose of low molecular weight heparin
• •Subjects must have normal thyroid function within 21 days of study entry as defined below: ≤ 3 X institutional ULN
• •Women of childbearing potential must have a negative pregnancy test within 21 days of study entry. Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and through 30 days after the last dose of study drug. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Men of reproductive potential treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and through 30 days after the last dose of study drug.
• •Patients must be able to swallow whole tablets.
• •Patients must have the following minimum intervals from prior treatments: surgery - 4 weeks, nitrosoureas - 6 weeks, cytotoxic chemotherapy - standard intervals depending on the most recent regimen. i.e., for temozolomide 5 of 28, 23 days after most recent temozolomide; for temozolomide 21 of 28 days, 7 days after most recent dose; etoposide 14 of 21 days, 7 days after last dose. For drugs not listed, the research nurse, treating investigator, and principal investigator will determine the appropriate interval, Investigational therapy or non-cytotoxic therapy - 2 weeks, For bevacizumab - 4 weeks from anticipated date of protocol surgery
• •Patients positive for human immunodeficiency virus (HIV) are allowed on study (note: HIV testing is not required), but HIV-positive patients must have: An undetectable viral load within 6 months of registration, A stable regimen of highly active anti-retroviral therapy (HAART), No requirement for concurrent antibiotics or antifungal agents for the prevention of opportunistic infections
• •For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
• •Patient must be deemed by investigator to be a candidate for post-operative chemotherapy.
• •Subjects must have the ability to understand and the willingness to sign a written informed consent document.