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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if the drug posaconazole can reach and affect brain tumors known as glioblastomas. Although typically used for fungal infections, researchers believe posaconazole might also inhibit the growth of brain tumor cells. Participants will take posaconazole before surgery to assess its effectiveness against these challenging tumors. Individuals with glioblastoma who plan to undergo surgery may qualify for this trial. As an Early Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants an opportunity to contribute to groundbreaking medical knowledge.

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.

Is there any evidence suggesting that posaconazole is likely to be safe for humans?

Research shows that posaconazole is generally well-tolerated for treating fungal infections. As an approved medication, its safety is well-understood. In studies, patients have not reported any major effects on the brain, even when administered through an IV. This suggests that posaconazole might be safe for treating brain-related conditions.

Although this trial is in its early stages, the FDA approval of posaconazole for other uses provides some reassurance about its safety. However, since this is an early-phase study, complete safety information for its use in treating brain tumors is not yet available. Researchers will closely monitor participants to quickly address any side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about posaconazole for glioblastoma because it offers a novel approach to treating this aggressive brain cancer. Unlike standard treatments such as surgery, radiation, and chemotherapy, posaconazole is an antifungal medication that targets cancer cells through a different mechanism. Its potential to disrupt cell growth pathways unique to glioblastoma could lead to more effective management of the disease. Additionally, posaconazole is taken orally, which may provide a more convenient treatment option compared to traditional intravenous therapies.

What evidence suggests that posaconazole might be an effective treatment for glioblastoma?

Research has shown that posaconazole, a drug originally used to treat fungal infections, may help fight glioblastoma, a type of brain tumor. In lab studies, posaconazole slowed tumor growth and killed cancer cells by stopping them from dividing and growing. This trial will include some participants receiving posaconazole to further investigate its potential as a treatment for glioblastoma. Although these findings are early, they suggest posaconazole could be a useful treatment for glioblastoma if further studies confirm its effectiveness. ^{1 3 4 6 7}

Who Is on the Research Team?

Alireza Mansouri, MD

Principal Investigator

Milton S. Hershey Medical Center

Are You a Good Fit for This Trial?

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.

Life expectancy greater than 12 weeks

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10553142/

A Phase 0 Clinical Trial Protocol - PMC These results will demonstrate the role of PCZ in altering tumor metabolism and can support the need for future trials to explore its efficacy ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04825275

Study Details | NCT04825275 | Neuro-pharmacological ... Ketoconazole and posaconazole have shown efficacy in reducing tumor cell proliferation in in-vitro studies.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9403519/

Posaconazole inhibits the stemness of cancer ... In this study, we found that POS has potent cytotoxicity and inhibits cell viability and proliferation in GBM.

4. trials.braintumor.org trials.braintumor.org/trials/NCT04825275

a Phase 0 Clinical Trial - National Brain Tumor Society Ketoconazole and posaconazole have shown efficacy in reducing tumor cell proliferation in in-vitro studies. Furthermore, both have also shown efficacy, mediated ...

5. withpower.com withpower.com/trial/posaconazole-for-glioblastoma-6bcfa

Posaconazole for Glioblastoma · Info for Participants 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 ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/12848593/

Posaconazole: SCH 56592 Posaconazole [SCH 56592, SPRIAFIL, Noxafil] is an orally active triazole derivative that is in phase III trials with the Schering-Plough Research Institute ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2006/022003s000_noxafil_medr.pdf

22-003 - accessdata.fda.gov Posaconazole was studied in patients E 13 years. PROPRIETARY Name: Noxafil. NONPROPRIETARY Name: Posaconazole, SCH 56592. CHEMICAL Name: 2,5 ...