Health TrialsbyHealthPanel

Azoles Targeting Recurrent High Grade Gliomas

ConditionsBrain Tumor, RecurrentCancer, AdvancedGlioma of Brain
Trial statusNot yet recruiting
Trial phaseEarly Phase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorUniversity Health Network, Toronto

About 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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Age ≥18 years

Evidence of recurrent HGG that in the opinion of the treating team does not represent pseudoprogression and would require surgical resection

Karnofsky Performance Score (KPS) ≥ 60%

ECOG ≤ 2

Disqualifiers

1. Patients may not be receiving any other investigational agents while on study

Patients who have known allergy to KCZ, PCZ, 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

Trial design

Design model

Parallel

Treatments tested in this trial

  • Ketoconazole (KCZ)

    Drug

    Oral Tablet

  • Posaconazole (PCZ)

    Drug

    Delayed Release Oral Tablet

Treatment groups

30 Participants
are divided into 4 treatment groups
Group A: Ketoconazole (KCZ) Single Dose GroupExperimental treatment 1 intervention
Group B: Ketoconazole (KCZ) Repeated Dose GroupExperimental treatment 1 intervention
Group C: Posaconazole (PCZ) Single Dose groupExperimental treatment 1 intervention
Group D: Posaconazole (PCZ) Repeated Dose groupExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

1

Intratumoral concentrations of KCZ or PCZ

Time frame
Following either single dose regimen(4-24hours prior to surgery) or repeated dose regimen of KCZ( for 2-5 days) or PCZ( for 7-10 days)
2

Plasma concentrations of KCZ or PCZ

Time frame
Following either single dose regimen(4-24hours prior to surgery) or repeated dose regimen of KCZ(for 2-5 days) or PCZ(for 7-10 days)

Secondary outcomes

1

Assess Hexokinase 2 activity

enzyme activity measured using optical absorbance with a spectrophotometer

Time frame
Following either single dose regimen(4-24hours prior to surgery) or repeated dose regimen of KCZ(for 2-5 days) or PCZ(for 7-10 days) compared to archive tumor tissue from baseline
2

Assess the biological effects of KCZ or PCZ on metabolites within the glycolytic pathway

quantify presence/absence of metabolites using mass spectrometry

Time frame
Following either single dose regimen(4-24hours prior to surgery) or repeated dose regimen of KCZ(for 2-5 days) or PCZ(for 7-10 days) compared to archive tumor tissue from baseline
3

assess the biological effects of KCZ or PCZ on tumor proliferation

measured using ki-67 proliferation index

Time frame
Following either single dose regimen(4-24hours prior to surgery) or repeated dose regimen of KCZ(for 2-5 days) or PCZ(for 7-10 days) compared to archive tumor tissue from baseline
4

assess biological effects of KCZ or PCZ on tumor cell death

measured using TUNEL staining

Time frame
Following either single dose regimen(4-24hours prior to surgery) or repeated dose regimen of KCZ(for 2-5 days) or PCZ(for 7-10 days) compared to archive tumor tissue from baseline

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

University Health Network, Toronto

Lead sponsor

Source ClinicalTrials.gov

This trial is not recruiting at the moment. You can still explore other options: