None listed
Conditions
Brief summary
This is a study of an experimental anti-cancer drug called CYT997, which targets the blood supply of the tumour. In this study, CYT997 is given as a 24 hour intravenous (IV) infusion on day 2 of a 21 day treatment cycle over 3 cycles. In this study, CYT997 is given in combination with another commonly used standard chemotherapy drug called Carboplatin. You may be eligible to join this study if you have Relapsed Glioblastoma Multiforme and a life expectancy of more than two months. Most advanced cancers will eventually stop responding to cancer treatments. In this situation, for people who may be eligible for this drug trial, there may not be any alternative standard treatments. Participants will receive supportive care and symptomatic treatments during the trial, in addition to receiving CYT997 and Carboplatin. The major focus of this trial is to test the safety, tolerability and effectiveness of CYT997 when given in combination with Carboplatin in patients with Relapsed Glioblastoma Multiforme. This involves finding out the highest dose of CYT997 that can be given without causing severe side effects. The trial also aims to assess the effects (good and bad) that CYT997 may have on you and your cancer.
Interventions
Carboplatin (Area under curve (AUC) =5 intravenous administration) on day 1; and CYT997 (intravenous administration at dose selected during Phase Ib component) on day 2 of a 21 day cycle
Sponsors
YM BioSciences Australia Pty Ltd
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
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 magnetic resonance imaging (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 carmustine (BCNU) or lomustine (CCNU)). • Age = 18 years. • If patients are taking steroids, the dose must be stable for = 7 days. • Eastern Co-operative Oncology Group (ECOG) performance status = 2. • Life expectancy of greater than 2 months. • Patients must have adequate organ and marrow function as defined below: o Absolute neutrophil count = 1.5 × 109/L o Platelet count = 100 × 109/L o Total bilirubin within normal limits o Liver enzymes (Aspartate aminotransferase (AST) or alanine aminotransferase (ALT)) < 5 × upper limit of normal (ULN) o Creatinine within normal limits OR creatinine clearance = 60 mL/min/1.73 m2 for patients with creatinine levels above normal o 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 Human Immunodeficiency Virus (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 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; 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 low-dose 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 Toxicity 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 (bifasicular 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, 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
Outcome results
None listed