Neoplasms

All Conditions

Nervous System Diseases

Rare Diseases

Glioblastoma

Brain Neoplasms

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Anti-Infective Agents

All Drugs and Chemicals

Clotrimazole

Miconazole

Antifungal Agents

Posaconazole

Antiprotozoal Agents

Antiparasitic Agents

Enzyme Inhibitors

Cytochrome P-450 Enzyme Inhibitors

Hormones

Hormone Antagonists

Participants will be taking 300 mg of the study drug (three 100 mg tablets) by mouth twice a day the first day and then 300 mg once a day until the day of biopsy or surgery. On the day of biopsy or surgery, participants will take their medication the morning of their biopsy or surgery (before the operation). Participants will then take the last dose of the medication in the morning of the day after their biopsy or surgery. Participants will be given 12 days' worth of the study drug (pills) and verbally instructed how and when to take them.

Participants will not undergo any intervention.

Posaconazole Pill

Micaiah D Grien, BS

Dora Hunter, MPH

Alireza M Mansouri

Alireza Mansouri, MD

This research is being done to find out if the study drug (posaconazole) can enter brain tumors at a high enough amount to stop the tumor cells from dividing. Posaconazole is a drug which doctors already use for fungal infections and is thought to be able to effect tumor cells. As treatments for this type of brain tumor are limited, it is hoped that the results of this study will help to determine if the study drug should be studied further as a possible treatment.

Both ketoconazole and posaconazole are FDA-approved anti-fungal agents with a well-established side effect and safety profile. Ketoconazole and posaconazole have shown efficacy in reducing tumor cell proliferation in in-vitro studies. Furthermore, both have also shown efficacy, mediated at least in part through inhibition of HK2 activity, in animal models with dosing concentration and schedules that are documented as safe in humans. As a drug, posaconazole has a more predictable half-life than ketoconazole and has less off-target effects. Therefore, the proposed trial will focus on the role of posaconazole exclusively. As a first step, demonstration of adequate penetrance of study drug in brain and tumor tissue (pharmacokinetics) and biological effect (inhibition of glycolysis and subsequent tumor cell death) is necessary prior to large scale clinical studies. A total of 5 control participants will be included in this study as the investigator specifically wants to assess for pharmacodynamic differences too. The addition of a control group to this study rather to both the studies (ketoconazole study is a separate protocol) is because the investigator feels posaconazole may be a more promising drug for moving forward.

Plasma drug concentration measurements are an unreliable method to assess delivery of drugs across the blood-brain barrier. In contrast, intracerebral MDC monitoring allows for approximate measurements within extracellular fluid (ECF) sampling of the brain. MDC placement within the brain is not a novel technique and has been utilized routinely in the ICU setting to measure brain metabolism by sampling of ECF of traumatic brain injury patients \[59-61\].

MDC are now FDA-approved and are being placed routinely with intracranial pressure monitors. This method allows for continuous measurement of ECF within a tumor or normal tissue. The dialysis probe has a semipermeable membrane which is less than 1 mm in diameter into which two sections of microcatheter are fused. Previous studies have demonstrated the feasibility of keeping the catheters in place of critically injured patients for up to 2 weeks \[62-64\].

When placed at the time of surgical resection, the microcatheters are stereotactically implanted, placing the probe within the desired brain and/or tumor region. Externally, the catheter is connected to a syringe pump, which delivers a low flow rate (μl/min) of continuous perfusion fluid (Lactated Ringers or artificial CSF) and dialysate is collected in a microvial from the outlet tube. This sterile, single use catheter is minimally invasive and developed to achieve optimal diffusing characteristics similar to passive diffusion of a capillary blood vessel. Just as in the function of brain capillary vessel, water, inorganic ions and small organic molecules freely diffuse across the membrane of the probe, whereas proteins and protein bound compounds are impermeable. Additionally, lipophilic compounds are poorly recovered. Therefore, assessment of pharmacokinetics of drug using MDC provides valuable insight relevant to its anti-neoplastic properties.

Neuro-pharmacological Properties of Repurposed Posaconazole in Glioblastoma: A Phase 0 Clinical Trial

Assessment of the concentration versus time curves of drug in the dialysate fluid

Measured through the Grade and Frequency of adverse events, based on the CTCAE v5.0 criteria

Measured using a hexokinase assay on tumor tissue

Assessed based on the concentration versus time profile of lactate in the dialysate fluid

Assessed based on the concentration versus time profile of pyruvate in the dialysate fluid

National Cancer Institute (NCI)

Milton S. Hershey Medical Center

Assistant Professor, Department of Neurosurgery

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Neuro-pharmacological Properties of Repurposed Posaconazole in Glioblastoma: A Phase 0 Clinical Trial	NCT04825275	Glioblastoma Glioblastoma Mu... Glioblastoma Mu... Glioblastoma Mu...	Posaconazole Pi...	18 Years -	Milton S. Hershey Medical Center
Neuro-pharmacological Properties of Repurposed Posaconazole in Glioblastoma: A Phase 0 Clinical Trial	NCT04825275	Glioblastoma Glioblastoma Mu... Glioblastoma Mu... Glioblastoma Mu...	Posaconazole Pi...	18 Years -	Milton S. Hershey Medical Center

Spots Global Cancer Trial Database for posaconazole pill