Diffuse GliomaEarly Phase 1NCT07585851
Administration of Repurposed Ketoconazole in Glioma Patients
A Early Phase 1 study testing Ketoconazole in people with Diffuse Glioma and Diffuse Glioma, Grade I, run by Universitas Padjadjaran at 1 site in Indonesia.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diffuse Glioma, Diffuse Glioma, Grade I, Diffuse Glioma, Grade II
- What is being tested?
- Ketoconazole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteIndonesia
- Study dates
- 28 Feb 2023to Aug 2026
- Phase
- Early Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
Indonesia1 site
National Brain Center Hospital Prof. Dr. dr. Mahar Mardjono
Jakarta, Jakarta Special Capital Region, 13630
About this study
Official title: Administration of Repurposed Ketoconazole in Glioma Patients: Early Phase 1 Clinical Trial
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.
Read the detailed description
Gliomas, particularly high-grade variants like glioblastoma multiforme (WHO grade IV), represent a major challenge in neuro-oncology, comprising over 50% of gliomas and 17% of all primary brain tumors with an incidence of 5 per 100,000. These tumors exhibit marked intra-tumoral heterogeneity, aggressive angiogenesis, and reliance on aerobic glycolysis-converting glucose to lactate irrespective of oxygen levels-to fuel proliferation, invasion, and survival despite maximal safe resection followed by temozolomide-radiotherapy (Stupp protocol), which yields median survival of only 14.6 months.
Preclinical models of high-grade glioma (HGG) have demonstrated ketoconazole's disruption of this metabolic vulnerability by inhibiting hexokinase 2 (HK2), thereby curtailing glycolysis, promoting apoptosis, and curbing angiogenesis-effects achieved at pharmacologically safe doses without reliance on novel agents that struggle against the blood-brain barrier (BBB). Yet, critical gaps persist: ketoconazole's penetration into plasma and glioma tissue (both low- and high-grade) remains undocumented, precluding translation to efficacy trials amid BBB limitations that undermine many repurposed cancer therapies.
This early phase 1 trial addresses these uncertainties in primary gliomas through individualised pre-surgical dosing (single or repeated low doses) tailored to patient status and operative timing-followed by direct intra-operative sampling of tumor tissue and plasma for ketoconazole quantification. By quantifying ketoconazole concentrations directly in tumor tissue and plasma across all grade of gliomas, this early phase 1 trial determines achievable drug exposure levels and informs safe, effective dosing for subsequent efficacy studies.
- Conditions
- Diffuse Glioma, Diffuse Glioma, Grade I, Diffuse Glioma, Grade II, Diffuse Glioma, Grade III, Diffuse Glioma, Grade IV
- Being tested
- Ketoconazole
- Keywords
- Diffuse Glioma, Glioblastoma, Ketoconazole
- Medical subject headings
- Lymphoma, Follicular, Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KetoconazoleDrug
Dose: 400 mg (two 200 mg tablets) orally.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Ketoconazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
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].
- 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.
- 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.
- Daneshmend TK, Warnock DW. Clinical Pharmacokinetics of Ketoconazole. Clin Pharmacokinet. 1988;14(1).
Measured: Preoperative administration to intraoperative sampling (4-120 hours post-dose)
Secondary outcomes (3)
Time Interval vs Ketoconazole Concentration in Tumor Tissue and Plasma
Correlation between time from ketoconazole administration to tumor resection and ketoconazole concentrations in glioma tissue and plasma.
Measured: Preoperative administration to intraoperative sampling (4-120 hours post-dose)
Glioma Grade vs Ketoconazole Concentration in Tumor Tissue and Plasma
Correlation between glioma grade (grade I-IV) and ketoconazole concentrations in tumor tissue and plasma
Measured: 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
This multivariable analysis evaluates how glioma grade (LGG vs. HGG) and time interval from dosing to sampling independently influence ketoconazole concentrations in tumor tissue and plasma, after controlling for both covariates to quantify these effects and reveal penetration patterns.
Measured: Preoperative administration to intraoperative sampling (4-120 hours post-dose)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 May 2026
- Study start28 Feb 2023
- Primary completion25 Sep 2024
- Study completionAug 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diffuse GliomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- Universitas Padjadjaran
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Selfy Oswari, Universitas Padjadjaran
- Investigators
- Selfy Oswari, MD, Principal investigator, Universitas Padjadjaran
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07585851
- Sponsor's protocol ID
- NC-202604.01
- Status last verified
- May 2026
- First submitted
- 6 May 2026
- Last updated
- 14 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Administration of Repurposed Ketoconazole in Glioma Patients: Early Phase 1 Clinical Trial
- ClinicalTrials.gov ID
- NCT07585851
- Acronym / sponsor ID
- NC-202604.01
- Conditions
- Diffuse Glioma, Diffuse Glioma, Grade I, Diffuse Glioma, Grade II, Diffuse Glioma, Grade III, Diffuse Glioma, Grade IV
- Keywords
- Diffuse Glioma, Glioblastoma, Ketoconazole
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 80 participants (actual)
- Lead sponsor
- Universitas PadjadjaranUniversity, hospital or other
- Study start
- 28 Feb 2023 (actual)
- Primary completion
- 25 Sep 2024 (actual)
- Study completion
- Aug 2026 (estimated)
- First posted
- 14 May 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Gliomas, particularly high-grade variants like glioblastoma multiforme (WHO grade IV), represent a major challenge in neuro-oncology, comprising over 50% of gliomas and 17% of all primary brain tumors with an incidence of 5 per 100,000. These tumors exhibit marked intra-tumoral heterogeneity, aggressive angiogenesis, and reliance on aerobic glycolysis-converting glucose to lactate irrespective of oxygen levels-to fuel proliferation, invasion, and survival despite maximal safe resection followed by temozolomide-radiotherapy (Stupp protocol), which yields median survival of only 14.6 months.
Preclinical models of high-grade glioma (HGG) have demonstrated ketoconazole's disruption of this metabolic vulnerability by inhibiting hexokinase 2 (HK2), thereby curtailing glycolysis, promoting apoptosis, and curbing angiogenesis-effects achieved at pharmacologically safe doses without reliance on novel agents that struggle against the blood-brain barrier (BBB). Yet, critical gaps persist: ketoconazole's penetration into plasma and glioma tissue (both low- and high-grade) remains undocumented, precluding translation to efficacy trials amid BBB limitations that undermine many repurposed cancer therapies.
This early phase 1 trial addresses these uncertainties in primary gliomas through individualised pre-surgical dosing (single or repeated low doses) tailored to patient status and operative timing-followed by direct intra-operative sampling of tumor tissue and plasma for ketoconazole quantification. By quantifying ketoconazole concentrations directly in tumor tissue and plasma across all grade of gliomas, this early phase 1 trial determines achievable drug exposure levels and informs safe, effective dosing for subsequent efficacy studies.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ketoconazole Administration | Experimental | Drug: KetoconazoleEligible 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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) .
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| KetoconazoleDose: 400 mg (two 200 mg tablets) orally. | Drug | Ketoconazole Administration |
Primary outcome
Difference in Ketoconazole Concentrations Between Tumor Tissue and Plasma in Primary All-Grade Gliomas
Time frame: Preoperative administration to intraoperative sampling (4-120 hours post-dose)
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).
3 secondary outcomes
Time Interval vs Ketoconazole Concentration in Tumor Tissue and Plasma
Time frame: Preoperative administration to intraoperative sampling (4-120 hours post-dose)
Glioma Grade vs Ketoconazole Concentration in Tumor Tissue and Plasma
Time frame: 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
Time frame: Preoperative administration to intraoperative sampling (4-120 hours post-dose)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 May 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Selfy Oswari, MD principal investigator
Universitas Padjadjaran
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Ketoconazole in people with Diffuse Glioma and Diffuse Glioma, Grade I, run by Universitas Padjadjaran at 1 site in Indonesia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 14 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Indonesia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Difference in Ketoconazole Concentrations Between Tumor Tissue and Plasma in Primary All-Grade Gliomas (time frame: Preoperative administration to intraoperative sampling (4-120 hours post-dose)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 May 2026.