Inclusion Criteria:

• Patients must have histologically-confirmed glioblastoma multiforme that has progressed after initial surgery, radiation therapy and temozolomide chemotherapy.
• Measurable tumour must be present on gadolinium-enhanced MRI
• At least 3 months must have elapsed from completing radiation to minimize the possibility of pseudo-progression.
• At least 4 weeks since prior chemotherapy (6 weeks if the last regimen included BCNU or CCNU).
• Age => 18 years.
• If patients are taking steroids, the dose must be stable for = 7 days.
• ECOG performance status = 2.
• Life expectancy of greater than 2 months.

• Patients must have adequate organ and marrow function as defined below:

  • Absolute neutrophil count = 1.5 × 109/L
  • Platelet count = 100 × 109/L
  • Total bilirubin within normal limits
  • AST or ALT < 5 × upper limit of normal (ULN)
  • Creatinine within normal limits OR creatinine clearance = 60 mL/min/1.73 m2 for patients with creatinine levels above normal
  • Normal left ventricular ejection fraction on a gated blood pool scan or echocardiogram
• Must agree to use adequate contraceptive measures if indicated
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Patients who have received any other investigational agent in the preceding four weeks prior to commencing therapy in this study.
• Patients who have been previously treated with carboplatin or etoposide.
• Patients who are receiving phenytoin or carbamazepine.
• Patients with a history of allergic reactions attributed to compounds of similar chemical composition to CYT997 or other agents used in the study.
• Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, cardiac arrhythmia or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant or lactating women.
• Patients with immune deficiency, including HIV-positive patients.
• Patients with uncontrolled diarrhoea despite optimal medication and those with any history of acute gastrointestinal bleeding.
• Patients who are unable or unwilling to undergo MRI scanning
• Patients with the following conditions/treatments will be excluded: o Myocardial infarction or stroke within 6 months o Unstable angina pectoris or acute ischemic changes on ECG o History of diabetic retinopathy o Symptomatic peripheral arterial disease o Major surgery in the last 4 weeks o Evidence of intra-tumoural haemorrhage on imaging, except for stable grade-1 post-operative haemorrhage. o Current therapeutic anti-coagulation with warfarin or a heparin (excludes lowdose prophylactic heparin). o Uncontrolled hypertension o The need for any anti-arrhythmic drugs
• Patients with a baseline prolongation of the QTc interval of CTC grade 1 (QTc > 0.45- 0.47 sec) or greater.
• Patients with impaired cardiac function or clinically significant cardiac diseases, including any one of the following: • LVEF < 45% as determined by MUGA scan or echocardiogram; o complete left bundle branch block; o obligate use of a cardiac pacemaker; o congenital long QT syndrome; o history or presence of ventricular tachyarrhythmia; o presence of unstable atrial fibrillation (ventricular response > 100 bpm). Patients with stable atrial fibrillation are eligible, provided they do not meet any of the other cardiac exclusion criteria; o clinically significant resting bradycardia (< 50 bpm); o right bundle branch block + left anterior hemiblock (bifasicular block); o angina pectoris = 3 months prior to starting study drug; o acute MI = 3 months prior to starting study drug; or o other clinically significant heart disease (e.g., CHF, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen).
• Patients currently receiving treatment with medications known to prolong the QTc interval and/or to induce Torsades de Pointes arrhythmia.