Glioblastoma Clinical Trial
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.
Status | Recruiting |
Enrollment | 5 |
Est. completion date | January 2025 |
Est. primary completion date | December 2024 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: - 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 Exclusion Criteria: - 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). - Patients who are non-English speakers - Patients who are not capable of understanding the consent form and would need a legally authorized representative. |
Country | Name | City | State |
---|---|---|---|
United States | Penn State Milton S Hershey Medical Center | Hershey | Pennsylvania |
Lead Sponsor | Collaborator |
---|---|
Milton S. Hershey Medical Center |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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) | |
Primary | 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 | 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 | from Baseline to Visit 7 (14 days +/- 7 days post-op) | |
Secondary | Hexokinase activity assay- measured as a proportion of hexokinase enzyme activity in relation to positive control | Measured using a hexokinase assay on tumor tissue | Within 24 hours after tumor resection | |
Secondary | Concentration of lactate measured using mass spectrometry in resected tumor tissue | Measured using mass spectrometry | Immediately after biopsy or resection of tissue | |
Secondary | Concentration of pyruvate, measured using mass spectrometry in resected tumor tissue | Measured using mass spectrometry | Immediately after biopsy or resection of tissue | |
Secondary | Evaluate ketoconazole's effect on tumor proliferation in tumor tissue | Measured using Ki-67 proliferation index | Within 24 hours after biopsy or tumor resection | |
Secondary | Evaluate ketoconazole's effect on cell death in tumor tissue | Measured using TUNEL staining | Within 24 hours after biopsy or tumor resection | |
Secondary | Evaluate ketoconazole's effect on angiogenesis in tumor tissue | Based on expression of vascular endothelial growth factor (VEGF) | Within 24 hours after biopsy or tumor resection | |
Secondary | 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 | Over the same 24-hour period used to measure the concentration of drug | |
Secondary | 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 | Over the same 24-hour period used to measure the concentration of drug |
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