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Protocol Summary

Protocol No.
Prinicipal Investigator
Mansouri, Seyed Alireza
Age Group
Neuro-pharmacological properties of repurposed ketoconazole in glioblastomas: A Phase 0 clinical trial
This study will examine the neuro-pharmacological (pharmacokinetics and pharmacodynamics) profile of ketoconazole (KCZ), in people with primary or recurrent high-grade gliomas (HGGs) requiring open surgical resection.

Primary Study Endpoints: Establish the neuro-pharmacokinetic profile of ketoconazole, using microdialysis catheters (MDC). This will be based on the assessment of the concentration versus time curves of drug in the dialysate fluid, collected over a 24-hour period after surgery or biopsy.

Secondary Study Endpoints: Evaluate tolerability of preoperative steady-state dosing of ketoconazole, as measured through the Grade and Frequency of adverse events, based on the CTCAE v5.0 criteria. Evaluate pharmacodynamics properties of ketoconazole, based on Study drug s effect on Hexokinase 2 activity within tumor tissue, as measured using a hexokinase assay on tumor tissue following biopsy or resection; Study drug s effect on downstream metabolites within the glycolysis pathway (pyruvate and lactate) in biopsy or resected tumor tissue immediately after the biopsy or resection; Study drug s effect on tumor proliferation (using Ki-67 proliferation index), cell death (using
TUNEL staining), and angiogenesis (based on expression of VEGF) in tumor tissue; Correlation of ketoconazole pharmacokinetic profile with that of lactate and pyruvate, using MDC. This will be assessed based on the concentration versus time profile of lactate and pyruvate in the dialysate fluid, over the same 24-hour period used to measure the concentration of drug.
Applicable Disease Sites
Brain and Nervous System
Participating Institutions
Hershey Medical Center