Trial Review

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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00650949




Registration number
NCT00650949
Ethics application status
Date submitted
27/03/2008
Date registered
2/04/2008
Date last updated
3/05/2013

Titles & IDs
Public title
Efficacy Study of CYT997 in Combination With Carboplatin in Glioblastoma
Scientific title
A Phase Ib/II Study of CYT997 in Combination With Carboplatin in Relapsed Glioblastoma Multiforme
Secondary ID [1] 0 0
CCL08001
Universal Trial Number (UTN)
Trial acronym
Linked study record

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

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - CYT997
Treatment: Drugs - Carboplatin

Experimental: CYT997 -


Treatment: Drugs: CYT997
Escalating doses (100mg/m\^2 to 150mg/m\^2), 24-hour intravenous infusion on Day 2 of a 21-day cycle (Phase Ib component). Dose selected in Phase Ib component to be used for Phase II component.

Treatment: Drugs: Carboplatin
Intravenous infusion over 1 hour at area under the concentration-time curve (AUC)=5 on Day 1 of a 21-day cycle
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Safety and tolerability of escalating doses of CYT997 when given in combination with standard carboplatin therapy (Phase Ib component)
Timepoint [1] 0 0
Ongoing throughout therapy up until 30 days after last dose of CYT997
Primary outcome [2] 0 0
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] 0 0
6 months after initiation of therapy
Secondary outcome [1] 0 0
Objective response rate (ORR)
Timepoint [1] 0 0
Response is measured every second cycle of therapy
Secondary outcome [2] 0 0
Overall survival
Timepoint [2] 0 0
Baseline to study completion
Secondary outcome [3] 0 0
Safety and tolerability
Timepoint [3] 0 0
Measured continuously from study commencement through to 30 days after last dose of CYT997
Secondary outcome [4] 0 0
Effects on pharmacodynamic markers of vascular disruption and tumour apoptosis
Timepoint [4] 0 0
Measured during first cycle of therapy
Secondary outcome [5] 0 0
Pharmacokinetic analysis of carboplatin and CYT997 in combination
Timepoint [5] 0 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 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
Minimum age
18 Years
Maximum age
No limit
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 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
NA
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
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/11/2009
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/06/2011
Sample size
Target
Accrual to date
Final
20
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
Royal North Shore Hospital - St-Leonards
Recruitment hospital [2] 0 0
Gold Coast Hospital - Southport
Recruitment hospital [3] 0 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [4] 0 0
Monash Medical Centre - Melbourne
Recruitment postcode(s) [1] 0 0
2065 - St-Leonards
Recruitment postcode(s) [2] 0 0
4215 - Southport
Recruitment postcode(s) [3] 0 0
5042 - Bedford Park
Recruitment postcode(s) [4] 0 0
3168 - Melbourne

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Gilead Sciences
Address
Country

Ethics approval
Ethics application status

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

Contacts
Principal investigator
Name 0 0
Jason Lickliter, MD
Address 0 0
Peninsula Health
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

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

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT00650949