Posaconazole for Glioblastoma

Overseen By Micaiah D Grien, BS

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Milton S. Hershey Medical Center

Must not be taking: Anticonvulsants, Metronidazole, Rifamycins, others

Disqualifiers: Hepatitis, Addison's disease, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 8

Duration: 12 days

6 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

You may need to stop taking certain medications if they interfere with the study drug, posaconazole. Specifically, if you are taking medications like metronidazole, certain anti-convulsants, or drugs that affect posaconazole's metabolism, you might need to switch to alternatives or stop them. It's best to discuss your current medications with the study team to see if any changes are needed.

How does the drug Posaconazole differ from other treatments for glioblastoma?

Posaconazole is unique because it is primarily an antifungal drug with a broad spectrum of activity, and it is being explored for glioblastoma, a type of brain cancer, which is not its usual use. Its novel application in glioblastoma may involve its ability to penetrate tissues effectively, but this is different from standard cancer treatments that typically target cancer cells directly. ^{1 2 3 4 5}

What is the purpose of this trial?

This research is being done to find out if the study drug (posaconazole) can enter brain tumors at a high enough amount to stop the tumor cells from dividing. Posaconazole 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.

Research Team

Alireza Mansouri, MD

Principal Investigator

Milton S. Hershey Medical Center

Eligibility Criteria

Adults over 18 with glioblastoma, a type of brain tumor, who are expected to live more than 12 weeks and need surgery. They must be able to swallow pills, have good liver function, use birth control if needed, understand the study consent form, and follow the treatment plan. People can't join if they're on certain drugs that affect posaconazole or have specific health issues like severe allergies to azoles.

Inclusion Criteria

My liver tests are within the normal range required by the study.

I can swallow pills.

My doctor recommends surgery for my brain tumor.

Exclusion Criteria

Pregnant and breast feeding women

Patients who are non-English speakers

I cannot switch from metronidazole to another antibiotic more than 7 days before starting posaconazole.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 300 mg of posaconazole twice on the first day, then 300 mg once daily until the day after biopsy or surgery

12 days

Daily medication administration

Surgery/Biopsy

Participants undergo biopsy or tumor resection, with microdialysis catheters placed for pharmacokinetic assessment

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including pharmacokinetic and pharmacodynamic assessments

14 days

Up to 7 visits (in-person)

Treatment Details

Interventions

• Posaconazole

Trial Overview The trial is testing whether Posaconazole, a drug normally used for fungal infections, can reach high enough levels in brain tumors to stop cancer cells from growing. It's being considered as a new treatment option for glioblastoma because current treatments are limited.

Participant Groups

Group I: Posaconazole Experimental Treatment 1 Intervention

Participants will be taking 300 mg of the study drug (three 100 mg tablets) by mouth twice a day the first day and then 300 mg once 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). 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.

Group II: Control Active Control 1 Intervention

Participants will not undergo any intervention.

Posaconazole is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Noxafil for:

• Invasive Aspergillus infections
• Candidemia
• Oropharyngeal Candidiasis

Approved in United States as Noxafil for:

• Invasive Aspergillus infections
• Candidemia
• Oropharyngeal Candidiasis

Approved in Canada as Noxafil for:

• Invasive Aspergillus infections
• Candidemia
• Oropharyngeal Candidiasis

Who Is Running the Clinical Trial?

Milton S. Hershey Medical Center

Lead Sponsor

Trials

515

Recruited

2,873,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

Posaconazole is an effective antifungal agent approved for preventing and treating invasive fungal infections, particularly in patients with weakened immune systems, such as those undergoing stem cell transplants.

The new gastro-resistant tablet formulation of posaconazole offers significant pharmacokinetic advantages over the oral suspension, including improved absorption, less variability between patients, and the convenience of once-daily dosing, making it the preferred choice for optimizing treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Posaconazole: a review of the gastro-resistant tablet and intravenous solution in invasive fungal infections. McKeage, K.[2018]

A study using MRI on adult and juvenile Beagle dogs showed that the intravenous administration of posaconazole (Noxafil) did not affect brain ventricle volume over three months, indicating its safety regarding brain development in older dogs.

The research highlighted significant natural variability in brain ventricle sizes among dogs, which is important for accurately interpreting the effects of treatments like posaconazole and supports its potential use in children over two years of age.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnetic resonance imaging assessment of the ventricular system in the brains of adult and juvenile beagle dogs treated with posaconazole IV Solution. Hines, CD., Song, X., Kuruvilla, S., et al.[2015]

Posaconazole, currently in phase III clinical trials, demonstrates broad-spectrum antifungal activity against various fungi, including Candida, Aspergillus, and zygomycetes, making it a promising option for treating invasive fungal infections.

The drug is well tolerated with mild side effects, such as headaches and gastrointestinal issues, and has shown clinical efficacy in treating severe fungal infections that are resistant to existing therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Posaconazole: a broad-spectrum triazole antifungal. Torres, HA., Hachem, RY., Chemaly, RF., et al.[2014]

Posaconazole is a potent antifungal agent effective against a wide range of fungi, including Candida spp. and Aspergillus spp., and is particularly beneficial for immunocompromised patients, such as those undergoing chemotherapy or organ transplants.

Its absorption is significantly enhanced when taken with food, and it has a long half-life of 15-35 hours, making it important to administer it properly to ensure optimal therapeutic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic/pharmacodynamic profile of posaconazole. Li, Y., Theuretzbacher, U., Clancy, CJ., et al.[2021]

Posaconazole is an orally active triazole antifungal that is currently undergoing phase III clinical trials for treating serious opportunistic fungal infections, such as aspergillosis and candidiasis.

In addition to its primary indications, preclinical studies suggest that posaconazole may also be effective against Cryptococcus neoformans, which causes cryptococcosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Posaconazole: SCH 56592. [2019]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Posaconazole: a review of the gastro-resistant tablet and intravenous solution in invasive fungal infections. [2018]

2. United States pubmed.ncbi.nlm.nih.gov

Magnetic resonance imaging assessment of the ventricular system in the brains of adult and juvenile beagle dogs treated with posaconazole IV Solution. [2015]

3. United States pubmed.ncbi.nlm.nih.gov

Posaconazole: a broad-spectrum triazole antifungal. [2014]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Pharmacokinetic/pharmacodynamic profile of posaconazole. [2021]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Posaconazole: SCH 56592. [2019]