Status:
NOT_YET_RECRUITING
Azoles Targeting Recurrent High Grade Gliomas
Lead Sponsor:
University Health Network, Toronto
Conditions:
Brain Tumor, Recurrent
Cancer, Advanced
Eligibility:
All Genders
18+ years
Phase:
EARLY_PHASE1
Brief Summary
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, i...
Detailed Description
High grade gliomas (WHO grade III and IV)(HGG) are the most common malignant, and aggressive brain tumour in humans. Current understanding of the mechanisms contributing to their growth and progressio...
Eligibility Criteria
Inclusion
- 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
- Life expectancy greater than 12 weeks
- Adequate liver function defined as ALT, AST, ALP, GGT, bilirubin within 1.5x institutional upper limit of normal
- Potassium, calcium, and magnesium within normal limits (PCZ cohort)
- Adequate renal function defined as eGFR levels within 1.5x the institutional upper limit of normal (only for KCZ cohort)
- Ability to swallow medication
- Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) for the duration of study participation.
- Ability to understand and willingness to sign a written informed consent document
- Be able to comply with treatment plan, study procedures and follow-up examinations
Exclusion
- 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
- Patients with liver enzymes (ALT, AST, ALP, GGT, Bilirubin) \>1.5x above normal range for the laboratory performing the test
- ECG with QT \> 450 msec (PCZ cohort)
- Patients taking drugs known to prolong the QT interval (PCZ cohort)
- Patients who are taking metronidazole and cannot be safely moved to a different antibiotic greater than 7 days prior to starting KCZ therapy
- Patients who have taken any azoles within the last 3 months
- Patients who are taking any anti-convulsant medication that interferes with the cytochrome P450 pathway (e.g. phenytoin, phenobarbital, carbamazepine, etc.) and who cannot be switched to alternative medications such as keppra (levetiracetam)
- Uncontrolled intercurrent illness such as chronic hepatitis, acute hepatitis, or psychiatric illness/social situation that would limit compliance with study requirements
- Patients with a history of Addison's disease or other forms of adrenal insufficiency
- Patient with little or no stomach acid production (achlorhydria) are excluded from the KCZ cohort
- Pregnant and breast feeding women
- Patients with a history of any medical or psychiatric condition or laboratory abnormality that in the opinion of the investigator may increase the risks associated with the study participation or investigational product administration or may interfere with the interpretation of the results.
- Patients who are not available for follow-up assessments or unable to comply with study requirements.
- Patients who are currently taking medications that induce the metabolism of KCZ or PCZ, such as isoniazid, nevirapine, rifamycins (such as rifabutin, rifampin), St. John's wort, among others (see section 5.3 for full details).
- Patients who are currently taking medications for which the metabolism may be affected by KCZ or PCZ, which include but are not limited to: benzodiazepines (such as alprazolam, midazolam, triazolam), domperidone, eletriptan, eplerenone, ergot drugs (such as ergotamine), nisoldipine, drugs used to treat erectile dysfunction-ED or pulmonary hypertension (such as sildenafil, tadalafil), some drugs used to treat seizures (such as carbamazepine, phenytoin), some statin drugs (such as atorvastatin, lovastatin, simvastatin)
Key Trial Info
Start Date :
June 1 2024
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
June 1 2027
Estimated Enrollment :
30 Patients enrolled
Trial Details
Trial ID
NCT03763396
Start Date
June 1 2024
End Date
June 1 2027
Last Update
March 8 2024
Active Locations (1)
Enter a location and click search to find clinical trials sorted by distance.
1
Toronto Western Hospital
Toronto, Ontario, Canada, M5T 2S8