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 aclinically 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 daysof 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 upperlimit of normal (ULN), AST (SGOT) ≤ 3 X institutional ULN, ALT (SGPT) ≤ 3 Xinstitutional ULN, Calculated creatinine clearance > 50 mL/min, Prothrombintime/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 bothof the following criteria: No active bleeding or pathological condition that carriesa 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 stabledose of low molecular weight heparin

• Subjects must have normal thyroid function within 21 days of study entry as definedbelow: ≤ 3 X institutional ULN

• Women of childbearing potential must have a negative pregnancy test within 21 daysof study entry. Women of childbearing potential and men must agree to use adequatecontraception (hormonal or barrier method of birth control; abstinence) prior tostudy entry, for the duration of study participation, and through 30 days after thelast dose of study drug. Should a woman become pregnant or suspect she is pregnantwhile participating in this study, she should inform her treating physicianimmediately. Men of reproductive potential treated or enrolled on this protocol mustalso agree to use adequate contraception prior to the study, for the duration ofstudy 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 intervalsdepending on the most recent regimen. i.e., for temozolomide 5 of 28, 23 days aftermost recent temozolomide; for temozolomide 21 of 28 days, 7 days after most recentdose; etoposide 14 of 21 days, 7 days after last dose. For drugs not listed, theresearch nurse, treating investigator, and principal investigator will determine theappropriate 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 undetectableviral load within 6 months of registration, A stable regimen of highly activeanti-retroviral therapy (HAART), No requirement for concurrent antibiotics orantifungal agents for the prevention of opportunistic infections

• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBVviral load must be undetectable on suppressive therapy, if indicated.

• For patients with a history of hepatitis C virus (HCV) infection must have beentreated 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-operativechemotherapy.

• Subjects must have the ability to understand and the willingness to sign a writteninformed 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 orbiologic composition to methimazole.

• Subjects with uncontrolled intercurrent illness including, but not limited toongoing or active infection, symptomatic congestive heart failure, unstable anginapectoris, cardiac arrhythmia, or psychiatric illness/social situations that wouldlimit compliance with study requirements.

• Other prior or concurrent malignancy whose natural history or treatment has thepotential to interfere with the safety or efficacy assessment of the investigationalregimen are excluded. Otherwise, patients with prior or concurrent malignancy areeligible.

• 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 ofany 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 psychiatricillness/social situations that would, in the Investigator's judgment, make thepatient inappropriate for this study.