Neuro-pharmacological Properties of Repurposed Ketoconazole in Glioblastomas

NCT04869449 | Terminated Early Phase 1 DMC FDA Drug

• 1 other identifier: STUDY00014115
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

This research is being done to find out if the study drug (ketoconazole) can enter brain tumors at a high enough amount to stop the tumor cells from dividing. Ketoconazole 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; Ketoconazole; Anti-fungal agents

Outcome Measures

Primary Outcomes (2)

• Establish drug concentration versus time profile yielding maximum plasma concentration (Cmax)

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

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

• Establish drug concentration versus time profile yielding half-life pharmacodynamics

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

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

Secondary Outcomes (9)

• Frequency and severity of treatment-emergent adverse events as assessed by CTCAE v 5.0

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

• Hexokinase activity assay- measured as a proportion of hexokinase enzyme activity in relation to positive control

  Within 24 hours after tumor resection

• Concentration of lactate measured using mass spectrometry in resected tumor tissue

  Immediately after biopsy or resection of tissue

• Concentration of pyruvate, measured using mass spectrometry in resected tumor tissue

  Immediately after biopsy or resection of tissue

• Evaluate ketoconazole's effect on tumor proliferation in tumor tissue

  Within 24 hours after biopsy or tumor resection

Study Arms (1)

Ketoconazole

EXPERIMENTAL

Participants will be taking 400 mg of the study drug (two 200 mg tablets) by mouth twice 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) and in the evening after their biopsy or surgery (after 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: Ketoconazole

Interventions

Ketoconazole DRUG

400 mg (two 200 mg tablets) orally

Also known as: Nizoral

Ketoconazole

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 high-grade gliomas (HGG) that in the opinion of the treating team would require surgical resection
• Karnofsky Performance Score (KPS) ≥ 60%
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• Life expectancy greater than 12 weeks
• Adequate liver function defined as Alanine aminotransferase (ALT),Aspartate transaminase (AST), Alkaline phosphatase (ALP) within 1.5x institutional upper limit of normal
• Adequate renal function defined as estimated glomerular filtration rate (eGFR) levels within 1.5x the institutional upper limit of normal
• Ability to swallow medication
• 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.
• 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 ketoconazole or other azoles
• 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
• Patients with a history of acute or chronic hepatitis
• Patients with liver enzymes (ALT, AST, ALP) \>1.5x above normal range for the laboratory performing the test
• Patients who are taking metronidazole and cannot be safely moved to a different antibiotic greater than 7 days prior to starting ketoconazole therapy
• 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)
• Uncontrolled intercurrent illness such as chronic hepatitis, acute hepatitis, or psychiatric illness/social situation that would limit compliance with study requirements
• Patients with a history of Addison's disease or other forms of adrenal insufficiency
• Patient with little or no stomach acid production (achlorhydria)
• 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 ketoconazole, 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.
• Patients who are currently taking medications for which the metabolism may be affected by ketoconazole, 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).

Sponsors & Collaborators

• Milton S. Hershey Medical Center: lead

Study Sites (1)

Penn State Milton S Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

MeSH Terms

Conditions

Glioblastoma; Brain Neoplasms

Interventions

Ketoconazole

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

Intervention Hierarchy (Ancestors)

Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Alireza Mansouri

  Milton S. Hershey Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: April 13, 2021
• First Posted: May 3, 2021
• Study Start: May 11, 2022
• Primary Completion: May 12, 2022
• Study Completion: May 12, 2022
• Last Updated: January 7, 2026

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)