Administration of Repurposed Ketoconazole in Glioma Patients

NCT07585851 | Active Not Recruiting Early Phase 1 DMC

• 1 other identifier: NC-202604.01
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

This early phase 1 clinical trial tests whether ketoconazole, an antifungal drug, can penetrate primary glioma brain tumors through the blood-brain barrier at levels sufficient to disrupt tumor growth, based on preclinical studies targeting glucose metabolism. Gliomas, especially aggressive high-grade types (WHO grades III-IV), have limited treatments like surgery, radiation, or chemotherapy. Patients with low- or high-grade gliomas will receive single or repeated low doses of ketoconazole before scheduled surgery, tailored to their health and procedure timing. During surgery, drug levels will be measured in tumor tissue and plasma. Results will guide future trials exploring azole drugs as glioma therapies.

Conditions

Diffuse Glioma; Diffuse Glioma, Grade I; Diffuse Glioma, Grade II; Diffuse Glioma, Grade III; Diffuse Glioma, Grade IV

Keywords

Diffuse Glioma; Glioblastoma; Ketoconazole

Outcome Measures

Primary Outcomes (1)

• Difference in Ketoconazole Concentrations Between Tumor Tissue and Plasma in Primary All-Grade Gliomas

  Mean concentrations of ketoconazole measured in plasma and intratumoral tissue samples collected intraoperatively from patients with primary all-grade gliomas (grade I to IV) after preoperative single or fixed-dose administration. Ketoconazole concentrations in tumor and plasma will be summarized using descriptive statistics. The 400 mg preoperative dose was chosen in accordance with published pharmacokinetic safety data supporting its established tolerability across varying clinical conditions \[1-3\]. 1. Krishna G, et al. Effect of Varying Amounts of a Liquid Nutritional Supplement on the Pharmacokinetics of Posaconazole in Healthy Volunteers. Antimicrob Agents Chemother. 2009;53(11):4749-52. 2. Krishna G, et al. Pharmacokinetics and Absorption of Posaconazole Oral Suspension under Various Gastric Conditions in Healthy Volunteers. Antimicrob Agents Chemother. 2009;53(3):958-66. 3. Daneshmend TK, Warnock DW. Clinical Pharmacokinetics of Ketoconazole. Clin Pharmacokinet. 1988;14(1).

  Preoperative administration to intraoperative sampling (4-120 hours post-dose)

Secondary Outcomes (3)

• Time Interval vs Ketoconazole Concentration in Tumor Tissue and Plasma

  Preoperative administration to intraoperative sampling (4-120 hours post-dose)

• Glioma Grade vs Ketoconazole Concentration in Tumor Tissue and Plasma

  Preoperative administration to intraoperative sampling (4-120 hours post-dose)

• Effect of Glioma Grade and Time Interval on Ketoconazole Concentrations in Tumor Tissue and Plasma

  Preoperative administration to intraoperative sampling (4-120 hours post-dose)

Study Arms (1)

Ketoconazole Administration

EXPERIMENTAL

Eligible patients undergo baseline assessments including liver function tests, renal function, metabolic panel, medical history review, and current medication inventory to ensure safety. Participants receive a single oral dose of ketoconazole 400 mg, administered 4-24 hours prior to scheduled surgery. Oral intake with food optimizes dissolution in acidic gastric conditions and alcohol avoidance for 3 days post-treatment to mitigates hepatotoxicity risks. Dosing is adjusted or withheld based on clinical tolerance: ketoconazole can be given with Dexamethasone 4mg PO QID; if adverse effects occur, dose is reduced to 200 mg; administration is discontinued if patient condition precludes dosing.

Drug: Ketoconazole

Interventions

Ketoconazole DRUG

Dose: 400 mg (two 200 mg tablets) orally.

Ketoconazole Administration

Eligibility Criteria

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

You may qualify if:

• Participants aged 18 years or older.
• Radiological confirmation of an intra-axial primary brain tumor (all grades) requiring surgical intervention.
• Karnofsky Performance Status (KPS) of ≥60 and projected life expectancy exceeding 12 weeks.
• Normal liver function, indicated by alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels within 1.5x the upper limit of normal (ULN).
• Normal renal function, defined as urea within 16.6-48.5 mg/dL, creatinine within 0.67-1.17 mg/dL, and/or eGFR ≥90 (within 1.5x the institutional ULN) .
• Capacity to take oral medications.
• Women of reproductive age and all male participants must commit to effective contraception (e.g., hormonal methods) throughout the trial.
• Willingness and ability to provide written informed consent.
• Commitment to adhere to the protocol, including treatment, procedures, and scheduled follow-ups.

You may not qualify if:

• Known hypersensitivity to ketoconazole.
• Prior severe reactions (e.g., agranulocytosis, neutropenia) to ketoconazole or other azole antifungals used for parasitic conditions.
• History of acute or chronic hepatitis.
• Elevated liver enzymes (ALT, AST) or impaired renal function (urea, creatinine, eGFR) exceeding 1.5x ULN per local lab standards.
• Current use of metronidazole without ability to switch to an alternative antibiotic at least 7 days prior to ketoconazole initiation.
• Azole antifungal use within the preceding 3 months.
• Pregnancy or breastfeeding.
• Any coexisting medical, psychiatric, or lab abnormality that, per investigator judgment, heightens study risks or confounds data interpretation.
• Unavailability for follow-up or inability to fulfill protocol demands.
• Concurrent use of ketoconazole metabolic inducers (e.g., isoniazid, nevirapine, rifampin, rifabutin) without discontinuation option.

Sponsors & Collaborators

• Universitas Padjadjaran: lead

Study Sites (1)

National Brain Center Hospital Prof. Dr. dr. Mahar Mardjono

Jakarta, Jakarta Special Capital Region, 13630, Indonesia

Location

MeSH Terms

Conditions

Lymphoma, Follicular; Glioblastoma

Interventions

Ketoconazole

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Selfy Oswari, MD

  Universitas Padjadjaran

  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: MD, Neurosurgeon

Study Record Dates

• First Submitted: May 6, 2026
• First Posted: May 14, 2026
• Study Start: February 28, 2023
• Primary Completion: September 25, 2024
• Study Completion (Estimated): August 1, 2026
• Last Updated: May 14, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

ID (1)