Clinical Trial Finder

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 bischloroethylnitrosourea (BCNU) or Chloroethyl-Cyclohexyl-NitrosoUrea (CCNU)).

• - Age ≥ 18 years.

• - If patients are taking steroids, the dose must be stable for = 7 days.

• - Eastern Cooperative Oncology Group (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.

• - Aspartate aminotransferase (AST) or alanine aminotransferase (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.

• - Patients who have been previously treated with bevacizumab or other anti-angiogenesis or vascular-disrupting agents.

• - Patients who are receiving enzyme-inducing anticonvulsant drugs (EIACD) such as 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: - Myocardial infarction (MI) or stroke within 6 months.

• - History of stroke or transient ischemic attacks (TIAs) - Unstable angina pectoris or acute ischemic changes on ECG.

• - History of diabetic retinopathy.

• - Symptomatic peripheral arterial disease o Major surgery in the last 4 weeks.

• - Evidence of intra-tumoural haemorrhage on imaging, except for stable grade-1 post-operative haemorrhage.

• - Current therapeutic anti-coagulation with warfarin or a heparin (excludes lowdose prophylactic heparin).

• - Uncontrolled hypertension.

• - The need for any anti-arrhythmic drugs.

• - Presence of luminal stenosis of 50% or more in any of the extracranial or intracranial arteries supplying the brain, as measured by magnetic resonance angiography (MRA) at baseline.

• - Patients with a baseline prolongation of the QTc interval of Common Terminology Criteria (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: - Left ventricular ejection fraction (LVEF) < 45% as determined by multigated acquisition (MUGA) scan or echocardiogram; - complete left bundle branch block; - obligate use of a cardiac pacemaker; - congenital long QT syndrome; - history or presence of ventricular tachyarrhythmia; - 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; - clinically significant resting bradycardia (< 50 bpm); - right bundle branch block + left anterior hemiblock (bifascicular block); - angina pectoris = 3 months prior to starting study drug; - acute MI = 3 months prior to starting study drug; or.

• - other clinically significant heart disease (e.g., congestive heart failure (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.

Arms

Interventions