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Trial registered on ANZCTR


Registration number
ACTRN12608000158369
Ethics application status
Approved
Date submitted
27/03/2008
Date registered
2/04/2008
Date last updated
22/03/2011
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase Ib/II Study of CYT997 in Combination with Carboplatin in Relapsed Glioblastoma Multiforme
Scientific title
A Phase Ib/II Study of CYT997 in Combination with Carboplatin in Relapsed Glioblastoma Multiforme: Assessing Safety and Tolerability.
Secondary ID [1] 252203 0
CCL08001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Glioblastoma multiforme 2969 0
Condition category
Condition code
Cancer 3110 3110 0 0
Brain

Intervention/exposure
Study type
Interventional
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 [1] 2704 0
Treatment: Drugs
Comparator / control treatment
Historical control information from patients with relapsed glioblastoma multiforme
Control group
Historical

Outcomes
Primary outcome [1] 3999 0
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 [1] 3999 0
Ongoing throughout therapy up until 30 days after last dose of CYT997
Primary outcome [2] 4000 0
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 [2] 4000 0
6 months after initiation of therapy
Secondary outcome [1] 6734 0
Objective response rate (ORR)
Timepoint [1] 6734 0
Response is measured every second cycle of therapy
Secondary outcome [2] 6735 0
Overall survival
Timepoint [2] 6735 0
Continuous. No finite follow-up period.
Secondary outcome [3] 6736 0
Safety and tolerability
Timepoint [3] 6736 0
Measured continuously from study commencement through to 30 days after last dose of CYT997
Secondary outcome [4] 6737 0
Effects on pharmacodynamic markers of vascular disruption and tumour apoptosis
Timepoint [4] 6737 0
Measured during first cycle of therapy
Secondary outcome [5] 6738 0
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 [5] 6738 0
Assessed during first cycle of therapy

Eligibility
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
Sex
Both males and females
Can healthy volunteers participate?
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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1 / Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
22/09/2008
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
35
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 3229 0
Commercial sector/Industry
Name [1] 3229 0
YM BioSciences Australia Pty Ltd
Country [1] 3229 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
YM BioSciences Australia Pty Ltd
Address
Level 2, 499 St Kilda Road, Melbourne, VIC 3004
Country
Australia
Secondary sponsor category [1] 2891 0
None
Name [1] 2891 0
Address [1] 2891 0
Country [1] 2891 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 5214 0
Southern Health Human Research Ethics Committee
Ethics committee address [1] 5214 0
Ethics committee country [1] 5214 0
Australia
Date submitted for ethics approval [1] 5214 0
17/03/2008
Approval date [1] 5214 0
03/09/2008
Ethics approval number [1] 5214 0
08045A
Ethics committee name [2] 6824 0
Northern Sydney and Central Coast Health Services Human Research Ethics Committee
Ethics committee address [2] 6824 0
Ethics committee country [2] 6824 0
Australia
Date submitted for ethics approval [2] 6824 0
Approval date [2] 6824 0
18/12/2008
Ethics approval number [2] 6824 0
0810-219M(CTN)
Ethics committee name [3] 6825 0
Flinders Clinical Recearch Ethics Committee
Ethics committee address [3] 6825 0
Ethics committee country [3] 6825 0
Australia
Date submitted for ethics approval [3] 6825 0
Approval date [3] 6825 0
30/03/2009
Ethics approval number [3] 6825 0
13/09
Ethics committee name [4] 259304 0
Gold Coast Health Services District Ethics Committee
Ethics committee address [4] 259304 0
Ethics committee country [4] 259304 0
Australia
Date submitted for ethics approval [4] 259304 0
Approval date [4] 259304 0
Ethics approval number [4] 259304 0
HREC/09/QGC/54

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 28471 0
Address 28471 0
Country 28471 0
Phone 28471 0
Fax 28471 0
Email 28471 0
Contact person for public queries
Name 11628 0
Ms Juliana Tasevska
Address 11628 0
Level 2, 499 St Kilda Road, Melbourne, VIC 3004
Country 11628 0
Australia
Phone 11628 0
+61 3 9926 0404
Fax 11628 0
Email 11628 0
[email protected]
Contact person for scientific queries
Name 2556 0
Dr Gregg Smith
Address 2556 0
Level 2, 499 St Kilda Road, Melbourne, VIC 3004
Country 2556 0
Australia
Phone 2556 0
+61 3 9926 0406
Fax 2556 0
+61 3 9926 0499
Email 2556 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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