Ketoconazole for Brain Cancer
Recruiting in Palo Alto (17 mi)
Overseen byAlireza Mansouri
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase < 1
Waitlist Available
Sponsor: Milton S. Hershey Medical Center
No Placebo Group
Trial Summary
What is the purpose of this trial?
This trial is testing posaconazole, a drug usually used for fungal infections, to see if it can help treat brain tumors by stopping the tumor cells from growing. The study focuses on patients with limited treatment options for their brain tumors.
Will I have to stop taking my current medications?
The trial requires that you stop taking certain medications that interact with ketoconazole, such as some antibiotics, anti-seizure drugs, and medications for erectile dysfunction or pulmonary hypertension. If you are on these medications, you may need to switch to alternatives or stop them before joining the trial.
How does the drug ketoconazole differ from other treatments for brain cancer?
Ketoconazole is unique because it is an antifungal drug that has shown potential in treating certain cancers by inhibiting cell growth, although it is not a standard treatment for brain cancer. It works by blocking the synthesis of ergosterol, a key component of fungal cell membranes, and has been used in other conditions like prostate and breast cancer.12345
Eligibility Criteria
Adults with high-grade gliomas needing surgery can join this trial if they're in good enough health, can swallow pills, and have a life expectancy over 12 weeks. They must agree to use birth control and be able to follow the study plan. People who've had bad reactions to similar drugs, are pregnant or breastfeeding, have certain illnesses like hepatitis or psychiatric conditions that could affect participation, or take specific medications that interact with ketoconazole cannot participate.Inclusion Criteria
I can take care of myself and am up and about more than half of my waking hours.
I am 18 years old or older.
You are expected to live for at least 12 more weeks.
See 8 more
Exclusion Criteria
You are allergic to ketoconazole or similar medications called azoles.
I have a history of hepatitis.
I cannot switch from metronidazole to another antibiotic 7 days before starting ketoconazole.
See 14 more
Treatment Details
Interventions
- Ketoconazole (Antifungal Agent)
Trial OverviewThe trial is testing whether ketoconazole, a drug normally used for fungal infections, can reach brain tumors in sufficient amounts to stop tumor growth. The goal is to see if it's effective against brain cancer cells and should be researched further as a treatment option.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: KetoconazoleExperimental Treatment1 Intervention
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.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Penn State Milton S Hershey Medical CenterHershey, PA
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Who Is Running the Clinical Trial?
Milton S. Hershey Medical CenterLead Sponsor
References
Cytotoxicity of ketoconazole in malignant cell lines. [2019]The cytotoxic effects of ketoconazole, an antifungal agent known to have some activity against human prostate cancer, adrenal cancer, and male metastatic breast cancer, were evaluated using colony-growth and clonogenic assays in eight malignant cell lines. The cytotoxicity of ketoconazole showed a dose- and time-dependent pattern, with the following concentrations inhibiting 90% of the growing colonies (IC90): MCF 7 (human breast cancer) 7.25 micrograms/ml, T 47 D (human breast cancer) 9.0 micrograms/ml, MiaPaCa (human pancreatic carcinoma) 10.0 micrograms/ml, COLO 357 (human pancreatic carcinoma), 9.5 micrograms/ml, HCT 8 (human colonic adenocarcinoma) 27.1 micrograms/ml, DU 145 (human prostatic cancer) 40.0 micrograms/ml, AR 42 J (rat pancreatic carcinoma) 9.0 micrograms/ml, and L1210 (murine leukemia) 8.6 micrograms/ml. Since a concentration of 10 micrograms/ml can be achieved in humans, the use of ketoconazole in human malignancies might be worthy of clinical evaluation.
Pharmacokinetics and dose proportionality of ketoconazole in normal volunteers. [2021]Ketoconazole is an orally effective, broad-spectrum, systemic antifungal agent. The pharmacokinetics and bioavailability of ketoconazole given as a 200-mg single dose in a tablet, suspension, or solution were studied in 24 fasting healthy males by using a crossover design. Levels of ketoconazole in plasma were determined for up to 48 h by a sensitive reverse-phase high-performance liquid chromatography method. The absorption of ketoconazole was rapid, with mean maximum concentrations of the drug in plasma of 4.2, 5.0, and 6.2 micrograms/ml attained at 1.7, 1.2, and 1.0 h, respectively, after administration of the tablet, suspension, and solution, respectively. The mean distribution and elimination half-life values were 1.5 to 1.7 and 7.5 to 7.9 h, respectively. The mean oral clearance of the solution dose was 209 (+/- 82.9 [standard deviation]) ml/min, and the mean apparent volume of distribution was 88.31 (+/- 68.72) liters. The relative bioavailabilities for the tablet and suspension were 81.2 (+/- 33.5) and 89.0 (+/- 23.1)%, respectively, of that of the solution. The data indicated the bioequivalence of the tablet to the suspension and of the suspension of the solution. Dose proportionality of ketoconazole was also studied in 12 volunteers after they received solution doses of 200, 400, and 800 mg. Linear correlations between the dose and the maximum concentration of the drug in plasma, the time to the maximum concentration, and the area under the concentration-time curve were observed. However, the increase in the area under the curve was more than proportional to the dose given. The levels in plasma seemed to decay at a lower rate after 400- and 800-mg doses. The mean oral clearance decreased from 244.9 to 123.6 and 80.0 ml/min, respectively, as the dose increased from 200 to 400 and 800 mg. The apparent dose-dependent kinetics may have been due to the presystemic elimination and capacity-limited hepatic metabolism which become saturated at higher doses.
Evaluation of ketoconazole. [2013]The pharmacology, microbiology, pharmacokinetics, clinical use, adverse effects, dosage and administration, and drug interactions of ketoconazole are reviewed. Ketoconazole, a new orally active antifungal agent, is an imidazole derivative structurally related to miconazole and clotrimazole. It impairs the synthesis of ergosterol (the main sterol in fungal cell membranes) in susceptible organisms, including yeast (Candida and Cryptococcus spp.), fungi, and dermatophytes. Ketoconazole is absorbed from the gastrointestinal tract; it is better absorbed from acidic aqueous solutions, so drugs that alter the pH of the stomach affect ketoconazole absorption. Therapeutic plasma concentrations are maintained for several hours following ketoconazole administration. Ketoconazole distributes readily into blood, urine, saliva, joint fluid, sebum, and cerumen; recent data indicate it may penetrate into cerebrospinal fluid as well. Elimination is biphasic, with a half-life of two hours during the first 10 hours following a dose, and a half-life of eight hours thereafter. Ketoconazole is metabolized by the hepatic microsomal oxidation system; metabolites are excreted renally. Ketoconazole is effective in treatment of several local and systemic fungal infections. It is approved by FDA for treating candidiasis, chronic mucocutaneous candidiasis, oral thrush, candiduria, coccidioidomycosis, histoplasmosis, chromomycosis, and paracoccidioidomycosis. Ketoconazole has also shown promise in other conditions not yet approved by FDA, including dermatophytosis, pityriasis versicolor, and vaginal candidosis. Controlled, comparative, double-blind trials of ketoconazole versus older agents are generally unavailable. Nausea and vomiting are the most common adverse effects encountered with ketoconazole. Transient elevations in serum liver enzymes have been noted occasionally. Initial daily ketoconazole dosage is 200 mg taken with a meal; 400 mg daily has been used for some conditions. Ketoconazole is a promising new drug, especially when one considers other available antifungal agents. However, large-scale comparative studies are not yet available; a more definitive evaluation of efficacy and safety, especially when the drug is used for long periods of time, must await more widespread use of ketoconazole.
Ketoconazole therapy of murine cryptococcal meningitis. [2013]Currently, even optimal therapy of cryptococcal meningitis is associated with appreciable mortality, drug toxicity, and prolonged hospitalization. Ketoconazole, a new oral imidazole, has therefore been evaluated in a murine model of cryptococcosis. Cryptococcal meningitis was induced in BALB/c mice by intracranial injection of Cryptococcus neoformans. The mice developed infection characterized by diffuse meningitis and extracerebral dissemination. Oral ketoconazole therapy prolonged survival of infected mice, but most mice ultimately succumbed to infection. Ketoconazole dramatically reduced the cryptococcal counts in the liver, but had minimal effect on counts in the brain. Paralleling these results were high concentrations of ketoconazole found in lung, spleen, and heart muscle and lower concentrations (2 to 5 micrograms/ml) found in the brain. The detection of biologically active drug in the brain, and the prolongation of survival afforded by ketoconazole, suggest a potential role for this agent in the theory of cryptococcal meningitis.
Ketoconazole in the treatment of cryptococcosis of the central nervous system. [2019]Two patients with cryptococcosis of the CNS were treated with ketoconazole (KTZ), an imidazole derivative with fungistatic properties: they had either failed standard therapy (Amphotericin-B + 5-Fluorocytosine) or suffered intolerable side-effects to it. Both patients were administered KTZ 800 mg/day as monotherapy for six months without interruption and both responded. One month after KTZ therapy was withdrawn, however, a relapse of the infection was seen in one case. Side-effects were minimal during the trial of treatment. KTZ could be a useful drug in some cases of neurocryptococcosis.