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. For patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load 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. Exclusion Criteria: Prior treatment toxicities not resolved to ≤ Grade 1 according to NCI CTCAE Version 5.0 except alopecia and neuropathy. Subjects receiving any other investigational agents. History of allergic reactions attributed to compounds of similar chemical or biologic composition to methimazole. Subjects with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. Other prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen are excluded. Otherwise, patients with prior or concurrent malignancy are eligible. Significant chronic gastrointestinal disorder with diarrhea as a major symptom (e.g., Crohn's disease, malabsorption, or Grade ≥2 (National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events Version 5.0 [CTCAE v.5.0] diarrhea of any etiology at screening). Pregnant or breastfeeding. Known history of hyperthyroidism or hypothyroidism Unable or unwilling to swallow tablets. Evidence of significant medical illness, abnormal laboratory finding, or psychiatric illness/social situations that would, in the Investigator's judgment, make the patient inappropriate for this study.