30 Participants Needed

Ketoconazole + Posaconazole for Recurrent Brain Cancer

Age: 18+
Sex: Any
Trial Phase: Phase < 1
Sponsor: University Health Network, Toronto
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

High-grade gliomas are the most common and aggressive type of brain cancer. Scientists don't fully understand how they grow and spread, and treatments haven't improved much in recent years. However, it's been discovered that these cancers rely heavily on using glucose to maintain their cancerous traits. In lab tests, drugs from the azole class, which target a key step in glucose metabolism, have shown promise in reducing tumor growth in these cancers. Researchers now want to test two of these drugs, ketoconazole and posaconazole, in patients with recurring high-grade gliomas. A small group of these patients will receive either one or several doses of these drugs before undergoing surgery. During the surgery, doctors will measure how much of the drug is present in the brain. They will also study how the drug affects the tumor, particularly its ability to process glucose. This research aims to provide initial insights into how these drugs work in patients with this type of brain cancer, which could guide future research and treatment strategies.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications that interact with the study drugs, such as some anti-seizure medications, certain antibiotics, and drugs that affect heart rhythm. If you're on any of these, you may need to switch to alternatives before joining the trial.

How is the drug combination of Ketoconazole and Posaconazole unique for treating recurrent brain cancer?

The combination of Ketoconazole and Posaconazole is unique for treating recurrent brain cancer because it involves two antifungal drugs that may have a novel mechanism of action against cancer cells, unlike traditional chemotherapy or radiation treatments. This approach is different from standard treatments, which often do not include antifungal agents.12345

What data supports the effectiveness of the drug combination Ketoconazole and Posaconazole for recurrent brain cancer?

The CUSP9 protocol, which includes Ketoconazole, has been proposed to improve outcomes in recurrent glioblastoma by using a combination of drugs that are well-tolerated and interfere with glioblastoma growth mechanisms. This suggests that Ketoconazole may have potential benefits in treating recurrent brain cancer when used as part of a multi-drug regimen.15678

Who Is on the Research Team?

GZ

Gelareh Zadeh, MD, PhD

Principal Investigator

University Health Network/Toronto Western Hospital

Are You a Good Fit for This Trial?

Adults over 18 with recurrent high-grade gliomas (a type of aggressive brain cancer) who need surgery can join. They should be relatively stable (KPS ≥ 60%, ECOG ≤ 2), expected to live more than 12 weeks, and have good liver and kidney function. Women and men must use birth control during the study.

Inclusion Criteria

Life expectancy greater than 12 weeks
Potassium, calcium, and magnesium within normal limits (PCZ cohort)
I can care for myself but may need occasional help.
See 8 more

Exclusion Criteria

I have not taken azole medications in the last 3 months.
Patients may not be receiving any other investigational agents while on study
Patients who have known allergy to KCZ, PCZ, or other azoles
See 15 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either a single dose or repeated doses of ketoconazole or posaconazole before surgery

1-10 days
1 visit (in-person) for surgery

Surgery

Surgery is performed to measure drug concentration in the brain and assess biological effects on the tumor

1 day
1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

  • Ketoconazole
  • Posaconazole
Trial Overview The trial is testing Ketoconazole (KCZ) and Posaconazole (PCZ), two drugs that may interfere with the tumor's glucose use, potentially slowing its growth. Participants will receive doses before their scheduled surgeries where drug levels in the brain and effects on the tumor will be assessed.
How Is the Trial Designed?
4Treatment groups
Experimental Treatment
Group I: Posaconazole (PCZ) Single Dose groupExperimental Treatment1 Intervention
Single dose 300 mg delayed release oral tablets 4-24 hours prior to surgery
Group II: Posaconazole (PCZ) Repeated Dose groupExperimental Treatment1 Intervention
300 mg delayed release oral tablets twice a day (BID) for day 1; every day thereafter is a single dose of 300 mg delayed release oral tablets. Total treatment time is 7-10 days prior to surgery.
Group III: Ketoconazole (KCZ) Single Dose GroupExperimental Treatment1 Intervention
Single dose 400mg oral tablets 4-24 hours prior to surgery
Group IV: Ketoconazole (KCZ) Repeated Dose GroupExperimental Treatment1 Intervention
400mg oral tablets twice a day (BID) for 2-5 days prior to surgery

Find a Clinic Near You

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials
1,555
Recruited
526,000+

Published Research Related to This Trial

Oral targeted agents, including BRAF inhibitors and various receptor inhibitors, show potential in treating brain metastases, but there is a lack of comprehensive data on their effectiveness in this specific area.
Many patients with brain metastases are excluded from clinical trials, leading to a significant gap in research and documentation of the intracranial activity of these therapies, highlighting the need for more focused investigations.
Oral Targeted Therapies and Central Nervous System (CNS) Metastases.Gabay, MP., Wirth, SM., Stachnik, JM., et al.[2022]
Patupilone, a chemotherapy drug, showed a progression-free survival rate of 36% in patients with non-small cell lung cancer (NSCLC) and brain metastases, indicating its potential efficacy in this challenging population.
The treatment was associated with significant adverse events, including diarrhea (24%) and pulmonary embolisms (8%), leading to all patients discontinuing the drug, highlighting the need for careful monitoring of side effects.
Multicenter phase 2 study of patupilone for recurrent or progressive brain metastases from non-small cell lung cancer.Nayak, L., DeAngelis, LM., Robins, HI., et al.[2018]

Citations

Oral Targeted Therapies and Central Nervous System (CNS) Metastases. [2022]
Dimeric small molecule agonists of EphA2 receptor inhibit glioblastoma cell growth. [2021]
A conceptually new treatment approach for relapsed glioblastoma: coordinated undermining of survival paths with nine repurposed drugs (CUSP9) by the International Initiative for Accelerated Improvement of Glioblastoma Care. [2023]
Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines on the Role of Emerging and Investigational Therapties for the Treatment of Adults With Metastatic Brain Tumors. [2019]
Standards of care for treatment of recurrent glioblastoma--are we there yet? [2022]
Salvage chemotherapy with paclitaxel for recurrent primary brain tumors. [2017]
Multicenter phase 2 study of patupilone for recurrent or progressive brain metastases from non-small cell lung cancer. [2018]
Vorinostat as a radiosensitizer for brain metastasis: a phase I clinical trial. [2021]
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