Neuro-pharmacological Properties of Repurposed Ketoconazole in Glioblastomas

Inclusion Criteria:

• Age ≥18 years

• Evidence of primary or recurrent high-grade gliomas (HGG) that in the opinion of thetreating team would require surgical resection

• Karnofsky Performance Score (KPS) ≥ 60%

• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2

• Life expectancy greater than 12 weeks

• Adequate liver function defined as Alanine aminotransferase (ALT),Aspartatetransaminase (AST), Alkaline phosphatase (ALP) within 1.5x institutional upper limitof normal

• Adequate renal function defined as estimated glomerular filtration rate (eGFR)levels within 1.5x the institutional upper limit of normal

• Ability to swallow medication

• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) for the duration of studyparticipation.

• Ability to understand and willingness to sign a written informed consent document

• Be able to comply with treatment plan, study procedures and follow-up examinations

Exclusion Criteria:

• Patients may not be receiving any other investigational agents while on study

• Patients who have known allergy to ketoconazole or other azoles

• Patients who have previously had a severe side effect, such as agranulocytosis andneutropenia, in conjunction with previous azole class drugs for a parasiticinfection

• Patients with a history of acute or chronic hepatitis

• Patients with liver enzymes (ALT, AST, ALP) >1.5x above normal range for thelaboratory performing the test

• Patients who are taking metronidazole and cannot be safely moved to a differentantibiotic greater than 7 days prior to starting ketoconazole therapy

• Patients who are taking any anti-convulsant medication that interferes with thecytochrome P450 pathway (e.g. phenytoin, phenobarbital, carbamazepine, etc.) and whocannot be switched to alternative medications such as keppra (levetiracetam)

• Uncontrolled intercurrent illness such as chronic hepatitis, acute hepatitis, orpsychiatric illness/social situation that would limit compliance with studyrequirements

• Patients with a history of Addison's disease or other forms of adrenal insufficiency

• Patient with little or no stomach acid production (achlorhydria)

• Pregnant and breast feeding women

• Patients with a history of any medical or psychiatric condition or laboratoryabnormality that in the opinion of the investigator may increase the risksassociated with the study participation or investigational product administration ormay interfere with the interpretation of the results.

• Patients who are not available for follow-up assessments or unable to comply withstudy requirements.

• Patients who are currently taking medications that induce the metabolism ofketoconazole, such as isoniazid, nevirapine, rifamycins (such as rifabutin,rifampin), or St. John's wort and cannot be safely discontinued off of them for theduration of the trial.

• Patients who are currently taking medications for which the metabolism may beaffected by ketoconazole, which include but are not limited to: benzodiazepines (such as alprazolam, midazolam, triazolam), domperidone, eletriptan, eplerenone,ergot drugs (such as ergotamine), nisoldipine, drugs used to treat erectiledysfunction (ED) or pulmonary hypertension (such as sildenafil, tadalafil), somedrugs used to treat seizures (such as carbamazepine, phenytoin), some statin drugs (such as atorvastatin, lovastatin, simvastatin).

• Patients who are non-English speakers

• Patients who are not capable of understanding the consent form and would need alegally authorized representative.