Neuro-pharmacological properties of repurposed posaconazole in glioblastoma: A Phase 0 clinical trial
Objective
Objectives Study Objectives This study will examine the neuro-pharmacological (pharmacokinetics and pharmacodynamics) profile of posaconazole (PCZ), in people with primary or recurrent high-grade gliomas (HGGs) requiring open surgical resection.
Primary Study Endpoints Establish the neuro-pharmacokinetic profile of posaconazole, using microdialysis catheters (MDC).
Secondary Study Endpoints Evaluate tolerability of preoperative steady-state dosing of posaconazole. Evaluate pharmacodynamics properties of posaconazole, based on Study drug s effect on Hexokinase 2 activity within resected tumor tissue Study drug s effect on downstream metabolites within the glycolysis pathway (Glucose-6-phosphate, Fructose-6-phosphate, Fructose-1,6-biphosphate, Dihydroxyacetone phosphate, 3-phosphglycerate, Phosphoenol pyruvate, Pyruvate, Ribose-6-phosphate, and Malate) in resected tumor tissue. c)Study drug s effect on tumor proliferation (Ki-67 proliferation index), cell death (TUNEL staining), and angiogenesis (expression of VEGF) in resected tumor tissue. d)Correlation of posaconazole pharmacokinetic profile with that of lactate and pyruvate, using MDC.
