GlioblastomaEarly Phase 1NCT04869449
Neuro-pharmacological Properties of Repurposed Ketoconazole in Glioblastomas
A Early Phase 1 study testing Ketoconazole in people with Glioblastoma and Glioblastoma Multiforme, run by Milton S. Hershey Medical Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma, Glioblastoma Multiforme, Glioblastoma Multiforme of Brain
- 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
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- 11 May 2022to 12 May 2022
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
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
- 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
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- 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
Who cannot join
- 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
Show all 17Show fewer
- 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).
- Patients who are non-English speakers
- Patients who are not capable of understanding the consent form and would need a legally authorized representative.
Trial locations and contacts
1 site in 1 country.
United States1 site
Penn State Milton S Hershey Medical Center
Hershey, Pennsylvania, 17033
About this study
Official title: Neuro-pharmacological Properties of Repurposed Ketoconazole in Glioblastomas: A Phase 0 Clinical Trial
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.
Read the detailed description
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 hexokinase 2 (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 microdialysis catheters (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.
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.
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.
- Conditions
- Glioblastoma, Glioblastoma Multiforme, Glioblastoma Multiforme of Brain, Glioblastoma Multiforme, Adult
- Being tested
- Ketoconazole
- Keywords
- Glioblastoma, Glioblastoma Multiforme, GBM, Brain cancer, Ketoconazole, Anti-fungal agents
- Medical subject headings
- Glioblastoma, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KetoconazoleDrug
Also called Nizoral
400 mg (two 200 mg tablets) orally
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Ketoconazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
Establish drug concentration versus time profile yielding maximum plasma concentration (Cmax)
Assessment of the concentration versus time curves of drug in the dialysate fluid
Measured: 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
Measured: 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
Measured through the Grade and Frequency of adverse events, based on the CTCAE v5.0 criteria
Measured: 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
Measured using a hexokinase assay on tumor tissue
Measured: Within 24 hours after tumor resection
Concentration of lactate measured using mass spectrometry in resected tumor tissue
Measured using mass spectrometry
Measured: Immediately after biopsy or resection of tissue
Concentration of pyruvate, measured using mass spectrometry in resected tumor tissue
Measured using mass spectrometry
Measured: Immediately after biopsy or resection of tissue
Evaluate ketoconazole's effect on tumor proliferation in tumor tissue
Measured using Ki-67 proliferation index
Measured: Within 24 hours after biopsy or tumor resection
Evaluate ketoconazole's effect on cell death in tumor tissue
Measured using TUNEL staining
Measured: Within 24 hours after biopsy or tumor resection
Evaluate ketoconazole's effect on angiogenesis in tumor tissue
Based on expression of vascular endothelial growth factor (VEGF)
Measured: Within 24 hours after biopsy or tumor resection
Correlation of concentration versus time profile of ketoconazole , compared to that of lactate - measured using mass spectrometry over 24 hours
Assessed based on the concentration versus time profile of lactate in the dialysate fluid
Measured: Over the same 24-hour period used to measure the concentration of drug
Correlation of concentration versus time profile of ketoconazole, compared to that of pyruvate - measured using mass spectrometry over 24 hours
Assessed based on the concentration versus time profile of pyruvate in the dialysate fluid
Measured: Over the same 24-hour period used to measure the concentration of drug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 May 2021
- Study start11 May 2022
- Primary completion12 May 2022
- Study completion12 May 2022
Why it stopped: Enrollment was stopped due to direction from the scientific review committee of the Penn State Cancer Institute. The instruction came due to slow accrual.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GlioblastomaStudies of the same condition, open and under way.
- More trials run by Milton S. Hershey Medical CenterThe sponsor's other registered studies.
- 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
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Milton S. Hershey Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Alireza Mansouri, Penn State Health Milton S Hershey Medical Center
- Investigators
- Alireza Mansouri, Principal investigator, Milton S. Hershey Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04869449
- Sponsor's protocol ID
- STUDY00014115
- Status last verified
- Nov 2025
- First submitted
- 13 Apr 2021
- Last updated
- 7 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neuro-pharmacological Properties of Repurposed Ketoconazole in Glioblastomas: A Phase 0 Clinical Trial
- ClinicalTrials.gov ID
- NCT04869449
- Acronym / sponsor ID
- STUDY00014115
- Conditions
- Glioblastoma, Glioblastoma Multiforme, Glioblastoma Multiforme of Brain, Glioblastoma Multiforme, Adult
- Keywords
- Glioblastoma, Glioblastoma Multiforme, GBM, Brain cancer, Ketoconazole, Anti-fungal agents
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Enrollment was stopped due to direction from the scientific review committee of the Penn State Cancer Institute. The instruction came due to slow accrual.
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Milton S. Hershey Medical CenterUniversity, hospital or other
- Study start
- 11 May 2022 (actual)
- Primary completion
- 12 May 2022 (actual)
- Study completion
- 12 May 2022 (actual)
- First posted
- 3 May 2021 (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 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.
Detailed description
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 hexokinase 2 (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 microdialysis catheters (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.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ketoconazole | Experimental | Drug: KetoconazoleParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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
Key exclusion criteria (17 listed)
- 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
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 |
|---|---|---|
| KetoconazoleAlso: Nizoral400 mg (two 200 mg tablets) orally | Drug | Ketoconazole |
Primary outcome
Establish drug concentration versus time profile yielding maximum plasma concentration (Cmax)
Time frame: Collected over a 24-hour period after surgery (biopsy or resection)
Assessment of the concentration versus time curves of drug in the dialysate fluid
Establish drug concentration versus time profile yielding half-life pharmacodynamics
Time frame: Collected over a 24-hour period after surgery (biopsy or resection)
Assessment of the concentration versus time curves of drug in the dialysate fluid
9 secondary outcomes
Frequency and severity of treatment-emergent adverse events as assessed by CTCAE v 5.0
Time frame: 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
Time frame: Within 24 hours after tumor resection
Concentration of lactate measured using mass spectrometry in resected tumor tissue
Time frame: Immediately after biopsy or resection of tissue
Concentration of pyruvate, measured using mass spectrometry in resected tumor tissue
Time frame: Immediately after biopsy or resection of tissue
Evaluate ketoconazole's effect on tumor proliferation in tumor tissue
Time frame: Within 24 hours after biopsy or tumor resection
Evaluate ketoconazole's effect on cell death in tumor tissue
Time frame: Within 24 hours after biopsy or tumor resection
Evaluate ketoconazole's effect on angiogenesis in tumor tissue
Time frame: Within 24 hours after biopsy or tumor resection
Correlation of concentration versus time profile of ketoconazole , compared to that of lactate - measured using mass spectrometry over 24 hours
Time frame: Over the same 24-hour period used to measure the concentration of drug
Correlation of concentration versus time profile of ketoconazole, compared to that of pyruvate - measured using mass spectrometry over 24 hours
Time frame: Over the same 24-hour period used to measure the concentration of drug
Results and safety
The study was stopped early (reason given: Enrollment was stopped due to direction from the scientific review committee of the Penn State Cancer Institute. The instruction came due to slow accrual.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jan 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.
Alireza Mansouri principal investigator
Milton S. Hershey Medical Center
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 Glioblastoma and Glioblastoma Multiforme, run by Milton S. Hershey Medical Center at 1 site in United States.
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 11 inclusion and 17 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: stopped early, as of the sponsor's last update on 7 Jan 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 United States. 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?
The study was stopped early (reason given: Enrollment was stopped due to direction from the scientific review committee of the Penn State Cancer Institute. The instruction came due to slow accrual.). Results are not available in the source record.
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?
Establish drug concentration versus time profile yielding maximum plasma concentration (Cmax) (time frame: Collected over a 24-hour period after surgery (biopsy or resection)). The study lists 2 primary outcomes in all. 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 7 Jan 2026.