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

NCT04825275 | Terminated Early Phase 1 Results DMC FDA Drug

• 2 other identifiers: STUDY000159481R03CA255992-01
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Glioblastoma; Glioblastoma Multiforme; Glioblastoma Multiforme of Brain; Glioblastoma Multiforme, Adult

Keywords

Glioblastoma; Glioblastoma Multiforme; GBM; Brain cancer; Posaconazole; Anti-fungal agents

Outcome Measures

Primary Outcomes (1)

• Posaconazole Concentration in Cerebrospinal Fluid Using Microdialysis Catheters

  Assessment of the concentration of drug in the dialysate fluid.

  Collected over a 24-hour period after surgery (biopsy or resection)

Secondary Outcomes (7)

• Number of Participants Able to Tolerate Preoperative Steady-state Dosing of Posaconazole

  from Baseline to Visit 7 (14 days +/- 7 days post-op)

• Posaconazole Effect on Hexokinase 2 Concentration Within Tumor Tissue

  Within 24 hours after biopsy or tumor resection

• Posaconazole Effect on Tumor Proliferation in Tumor Tissue

  Within 24 hours after biopsy or tumor resection

• Posaconazole Effect on Cell Death in Tumor Tissue

  Within 24 hours after biopsy or tumor resection

• Posaconazole Effect on Angiogenesis in Tumor Tissue

  Within 24 hours after biopsy or tumor resection

Study Arms (2)

Posaconazole

EXPERIMENTAL

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.

Drug: Posaconazole Pill

Control

NO INTERVENTION

Participants will not undergo any intervention.

Interventions

Posaconazole Pill DRUG

300 mg (three 100 mg tablets) orally

Also known as: Noxafil

Posaconazole

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years
• Evidence of primary or recurrent HGG that in the opinion of the treating team would require surgical resection
• Karnofsky Performance Score (KPS) ≥ 60%
• ECOG ≤ 2
• Life expectancy greater than 12 weeks
• Adequate liver function defined as ALT, AST, ALP within 1.5x institutional upper limit of normal (for study drug arm only)
• Ability to swallow medication (for study drug arm only)
• 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 study participation (for study drug arm only)
• 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

You may not qualify if:

• Patients may not be receiving any other investigational agents while on study
• Patients who have known allergy to posaconazole or other azoles (for study drug arm only)
• Patients who have previously had a severe side effect, such as agranulocytosis and neutropenia, in conjunction with previous azole class drugs for a parasitic infection (for study drug arm only)
• Patients with a history of acute or chronic hepatitis (for study drug arm only)
• Patients with liver enzymes (ALT, AST, ALP) \>1.5x above normal range for the laboratory performing the test (for study drug arm only)
• Patients who are taking metronidazole and cannot be safely moved to a different antibiotic greater than 7 days prior to starting posaconazole therapy (for study drug arm only)
• Patients who are taking any anti-convulsant medication that interferes with the cytochrome P450 pathway (e.g. phenytoin, phenobarbital, carbamazepine, etc.) and who cannot be switched to alternative medications such as keppra (levetiracetam) (for study drug arm only)
• Uncontrolled intercurrent illness such as chronic hepatitis, acute hepatitis, or psychiatric illness/social situation that would limit compliance with study requirements (for study drug arm only)
• Patients with a history of Addison's disease or other forms of adrenal insufficiency (for study drug arm only)
• Patient with little or no stomach acid production (achlorhydria) (for study drug arm only)
• Pregnant and breast feeding women)
• Patients with a history of any medical or psychiatric condition or laboratory abnormality that in the opinion of the investigator may increase the risks associated with the study participation or investigational product administration or may interfere with the interpretation of the results.
• Patients who are not available for follow-up assessments or unable to comply with study requirements.
• Patients who are currently taking medications that induce the metabolism of posaconazole, such as isoniazid, nevirapine, rifamycins (such as rifabutin, rifampin), or St. John's wort and cannot be safely discontinued off of them for the duration of the trial (for study drug arm only).
• Patients who are currently taking medications for which the metabolism may be affected by posaconazole, 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 erectile dysfunction-ED or pulmonary hypertension (such as sildenafil, tadalafil), some drugs used to treat seizures (such as carbamazepine, phenytoin), some statin drugs (such as atorvastatin, lovastatin, simvastatin) (for study drug arm only).

Sponsors & Collaborators

• Milton S. Hershey Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Penn State Milton S Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

Related Publications (1)

• Bhanja D, Neighbors J, Connor J, Zadeh G, Mansouri A. Neuropharmacological Study of Posaconazole for Glioblastoma: A Phase 0 Clinical Trial Protocol. Neurosurgery. 2022 Oct 1;91(4):658-665. doi: 10.1227/neu.0000000000002071. Epub 2022 Jul 25.

  PMID: 35861778 DERIVED

MeSH Terms

Conditions

Glioblastoma; Brain Neoplasms

Interventions

posaconazole

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Limitations and Caveats

A limitation in data analysis is failure to meet the enrollment goal. Enrollment was difficult due to the rare nature of the disease and the 7-10 day dosing window. Some patients were eligible, but immediate surgical intervention was necessary, so they could not reach steady-state posaconazole. Two planned outcome measures, correlation of neuro-pharmacokinetic profile with concentration of lactate and pyruvate, were not analyzed due to limited volume of cerebrospinal fluid from microdialysis.

Results Point of Contact

• Title: Alireza Mansouri, MD
• Organization: Penn State College of Medicine

connect@mansourimd.com

717-763-2559

Study Officials

• Alireza Mansouri, MD

  Milton S. Hershey Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor, Department of Neurosurgery

Study Record Dates

• First Submitted: March 25, 2021
• First Posted: April 1, 2021
• Study Start: May 13, 2022
• Primary Completion: November 6, 2024
• Study Completion: November 6, 2024
• Last Updated: January 23, 2026
• Results First Posted: December 17, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)