Ketoconazole Before Surgery in Treating Patients With Recurrent Glioma or Breast Cancer Brain Metastases

PRIMARY OBJECTIVES: I. To determine if ketoconazole alters the tGLI1 activation signature (tGAS) which is consisted of eight validated tGLI1 regulated genes (CD24, CD44, VEGF-A, VEGF-C, VEGFR2, TEM7, OCT-4. and heparanase) in tGLI1 expressing brain biospecimens. SECONDARY OBJECTIVES: I. To determine if pre-treatment with ketoconazole, an inhibitor of the tGLI1 pathway in tissue culture and animal models, reduces circulating tGLI1 associated exosomal miRNA expression (miR1290 and miR1246) in brain tumor patients. II. To describe the safety of ketoconazole when administered peri-operatively to patients with primary and secondary brain tumors. III. To measure the blood brain penetrance of ketoconazole in serum relative to enhancing brain tissue. EXPLORATORY OBJECTIVES: I. To measure blood brain penetration of ketoconazole in serum relative to cerebrospinal fluid (CSF) and serum relative to non-enhancing brain tissue (exploratory recurrent glioma patients only). II. To compare tGLI1 expression and pathway modulation with ketoconazole pre-treatment in patients with recurrent gliomas relative to breast cancer brain metastases (BCBM). III. To determine the overall survival and toxicity outcomes for patients that continue ketoconazole after surgery, at the discretion of the treating physician. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive ketoconazole orally (PO) once daily (QD) on days 1-4 before standard surgery in the absence of disease progression or unacceptable toxicity. ARM II: Patients undergo standard surgery. After completion of study treatment, patients are followed up at 30 days.