QOLP-23. PHASE II RANDOMISED PLACEBO-CONTROLLED DOUBLE-BLIND STUDY OF ACETAZOLAMIDE VERSUS PLACEBO FOR CEREBRAL OEDEMA IN RECURRENT AND/OR PROGRESSIVE HIGH-GRADE GLIOMA REQUIRING TREATMENT WITH DEXAMETHASONE

Abstract

INTERVENTION: Eligible participants will be randomised to the study in 1:1 ratio to either study treatment or control. The study treatment group will receive 1 tablet of 250 mg acetazolamide twice per day for 8 weeks. The placebo group will receive 1 tablet of placebo twice per day for 8 weeks. Drug accountability will be checked at each visit with bottle counts. CONDITION: Cerebral Oedema in recurrent and/or progressive High Grade Glioma PRIMARY OUTCOME: Composite endpoint of dexamethasone dose reduction and stability of neurological function, determined by: ; ; 1) At least 50% corticosteroid dose reduction from baseline (baseline dosage is considered the stable dose for at least 3 days prior to randomisation), achieved within 28 days from randomisation and maintained it for > 7 days ; ; AND ; ; 2) Without deterioration in neurological function (deterioration is defined as a decrease in Karnofsky Performance Status of 20 points or more) SECONDARY OUTCOME: Assess feasibility of study methodology and measures by assessing the accrual rate and the compliance to the treatment regimen. Patients will complete a daily dexamethasone dose diary. Composite outcome to describe the adverse effects attributable to dexamethasone as reported by clinicians (CTCAE v 4.03) and patient/caregiver self‐report (DSQ‐Chronic questionnaire) Composite outcome to describe toxicities attributable to acetazolamide (Worst toxicity as per CTCAE v 4.03) and patient and caregiver rated acetazolamide toxicity as reported by a purpose designed questionnaire) Evaluate symptoms of raised intracranial pressure over the study period. ; Symptoms of raised intracranial pressure including nausea, vomiting and headache will be coded and severity rated according to CTCAE v4.03 by the treating specialist during study visits. To document neurological function over the study period ; A structured fortnightly neurological examination will assess level of consciousness, mental status, vision, speech, cranial nerve abnormalities, motor and sensory loss in limbs, and gait or limb ataxia. The clinician will rate each variable from normal to severely abnormal according to specific criteria utilized in other studies INCLUSION CRITERIA: 1) Adults aged >or = 18 years; 2) Pathological diagnosis of HGG NOTE: HGG includes glioblastoma multiforme, anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic ependymoma, anaplastic oligoastrocytoma; 3) Clinically or radiologically diagnosed progressive and/or recurrent disease Recommencement of dexamethasone or dose increase indicated due to progressive raised ICP regardless of aetiology, minimum dose 4mg per day; 4) Stable dexamethasone dose (after dose increase or recommencement) for at least 72 hours before randomisation; 5) Baseline Karnofsky Performance Status of >or = 40 at baseline; 6) Ability to swallow oral medication; 7) Adequate liver function (Bilirubin < or = 2.5 times upper limit of normal; Alkaline phosphatase, aspartate transaminase and alanine transaminase 50 ml/min measured using Cockroft‐Gault; 9) Adequate haemat