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Trial Details
indicate updates made to monitored data item(s) since trial registration. These data item(s) are monitored to ensure they comply with the WHO / journal editors standards.
 
Request Number: 082702
ACTR Number: ACTRN12608000158369
Trial Status: Registered
Date Submitted: 27/03/2008
Date Registered: 2/04/2008

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Public title: A Phase Ib/II Study of CYT997 in Combination with Carboplatin in Relapsed Glioblastoma Multiforme
ANZCTR registration title: A Phase Ib/II Study of CYT997 in Combination with Carboplatin in Relapsed Glioblastoma Multiforme: Assessing Safety and Tolerability.
Secondary ID:CCL08001 
UTN:
Trial acronym:

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Health condition(s) or problem(s) studied:
Glioblastoma multiforme 
Condition category: Condition code:
Cancer Brain 

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Description of intervention(s) / exposure: 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
Intervention code:Treatment: drugs 
Comparator / control treatment: Historical control information from patients with relapsed glioblastoma multiforme
Control group: Historical

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Primary outcome 1:To assess the safety and tolerability of escalating doses of CYT997 when given in combination with standard carboplatin therapy (Phase Ib component). Dose escalation will cease once the Maximum Tolerated Dose has been identified and 6 patients have been treated at the Recommended Dose for Phase II. Safety and tolerability outcomes will be measured using the NCI CTCAE (v3) grading of adverse events. 
Timepoint:Ongoing throughout therapy up until 30 days after last dose of CYT997 
Primary outcome 2:To estimate the progression-free survival at 6 months (PFS-6) utilising the dose of CYT997 identified in the Phase Ib component of this study (Phase II component 
Timepoint:6 months after initiation of therapy 
Secondary outcome 1:Objective response rate (ORR) 
Timepoint:Response is measured every second cycle of therapy 
Secondary outcome 2:Overall survival 
Timepoint:Continuous. No finite follow-up period. 
Secondary outcome 3:Safety and tolerability 
Timepoint:Measured continuously from study commencement through to 30 days after last dose of CYT997 
Secondary outcome 4:Effects on pharmacodynamic markers of vascular disruption and tumour apoptosis 
Timepoint:Measured during first cycle of therapy 
Secondary outcome 5:Pharmacokinetic analysis of carboplatin and CYT997 in combination will be determined from blood samples taken at specified timepoints in cycles 1 and 2. Plasma samples will be analysed to establish blood concentrations of CYT997 and Carboplatin. 
Timepoint:Assessed during first cycle of therapy 

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Key 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
Minimum Age: 18 Years
Maximum Age: Not stated
Gender: Both males and females
Healthy volunteers? No
Key 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

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Study type: Interventional
Purpose of the study: Treatment
Allocation to intervention: Nonrandomised trial
Describe the procedure for enrolling a subject and allocating the treatment (allocation concealment procedures):
Describe the methods used to generate the sequence in which subjects will be randomised (sequence generation):
Masking / blinding: Open (masking not used)
Assignment: Single group
Other design features (specify):
Type of endpoint(s): Safety/efficacy

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Phase Phase 1 / Phase 2
Anticipated or actual date of first participant enrolement: 22/09/2008
Target sample size: 35
Recruitment status: Open to recruitment

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Funding source:Commercial sector/Industry 
Name:Cytopia Research Pty Ltd 
Address:Level 2, 499 St Kilda Road, Melbourne, VIC 3004 
Country:Australia 
Primary sponsor: Commercial sector/Industry
Name: Cytopia Research Pty Ltd
Address: Level 2, 499 St Kilda Road, Melbourne, VIC 3004
Country: Australia
Secondary sponsor:None 
Name: 
Address: 
Country: 
Other collaborator: 

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Has the study received approval from at least one ethics committee? Yes
Ethics Committee name 1:Southern Health Human Research Ethics Committee 
Address:Research Support Unit Level 4 Main Block Monash Medical Centre 246 Clayton Rd Clayton Victoria 3168 
Country:Australia 
Date of approval:3/09/2008 
HREC Number:08045A 
Ethics Committee name 2:Northern Sydney and Central Coast Health Services Human Research Ethics Committee 
Address:Research Office, Level 4 Vindin House Royal North Shore Hospital Pacific Highway St Leonards NSW 2065 
Country:Australia 
Date of approval:18/12/2008 
HREC Number:0810-219M(CTN) 
Ethics Committee name 3:Flinders Clinical Recearch Ethics Committee 
Address:Room 2A 221, Flinders Medical Centre Flinders Drive Bedford Park South Australia 5042 
Country:Australia 
Date of approval:30/03/2009 
HREC Number:13/09 
Ethics Committee name 4:Gold Coast Health Services District Ethics Committee 
Address:Gold Coast Hospital, 108 Nerang Street, Southport, Queensland 4215 
Country:Australia 
Date of approval: 
HREC Number:HREC/09/QGC/54 
Countries of recruitment:Australia 
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.
Trial website:
Presentations / publication list:

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Contact person for public queries
Name: Ms Juliana Tasevska
Address: Level 2, 499 St Kilda Road, Melbourne, VIC 3004
Country: Australia
Tel: +61 3 9926 0404
Fax:
Email: jtasevska@ymbiosciences.com.au

Contact person for scientific queries
Name: Dr Gregg Smith
Address: Level 2, 499 St Kilda Road, Melbourne, VIC 3004
Country: Australia
Tel: +61 3 9926 0406
Fax: +61 3 9926 0499
Email: gsmith@ymbiosciences.com.au

Contact person responsible for updating information
Name: Ms Juliana Tasevska
Address: Level 2, 499 St Kilda Road, Melbourne, VIC 3004
Country: Australia
Tel: +61 3 9926 0404
Fax: +61 3 9926 0499
Email: jtasevska@ymbiosciences.com.au
   
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