Phase III Randomized Double-blind Placebo-controlled Trial of Metformin for Cognitive Recovery and White Matter Growth in Paediatric Patients With a Brain Tumour
The efficacy of treatment with metformin for promoting cognitive recovery and brain growth in children/adolescents treated for a brain tumour will be investigated in a multi-site Phase III randomized double-blind placebo-controlled parallel arm superiority trial. Specifically, in children/adolescents aged 7 years to 21 years and 11 months who have completed treatment for a brain tumour, is oral administration of metformin for 16 weeks associated with greater improvement of cognitive function and brain growth compared to placebo administered for 16 weeks?
‣ In order to be eligible to participate in this study, an individual must meet all of the following criteria:
• No less than 3 weeks after completion of:
‣ Primary therapy for:
⁃ medulloblastoma
⁃ OR
• ependymoma
⁃ OR
• craniopharyngioma
⁃ OR
• germ cell tumours
⁃ OR
⁃ Primary therapy for any other brain tumour treated with cranial radiation - at the discretion of the Study PI
• OR
⁃ Cranial radiation for relapsed ependymoma
• Age 7 years to 21 years and 11 months at the time of enrollment
• Either declare English (or French in accepting sites) as their native language or have had at least two years of schooling in English (or French in accepting sites) at the time of consent
• Able to swallow tablets either whole, crushed or via a feeding tube and be willing to adhere to the study intervention regimen
• Meet criteria for normal organ function requirements as described below:
∙ Normal renal function defined as: Estimated glomerular filtration rate (eGFR) \> 75ml/min/1.73m²
⁃ eGFR is calculated using the Schwartz formula: eGFR (mL/min/1.73m²) = (0.41 × height in cm) / creatinine in mg/dL
‣ Normal liver function defined as:
⁃ Serum glutamic-oxaloacetic transaminase (SGOT) (AST) ≤2.5 x institutional upper limit of normal (ULN) for age and gender
• Serum glutamic pyruvic transaminase (SGPT) (ALT) ≤2.5 x institutional ULN for age and gender
• Total bilirubin \<1.5x institutional ULN for age and gender (patients with documented Gilbert's Disease may be enrolled with Sponsor approval and total bilirubin ≤2.0 x institutional ULN)
• Informed consent (and assent, where applicable) will be obtained from the participants and/or their legal guardian(s) by study team members delegated to consent for this study