Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/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
N/A
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
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
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
This study seeks to (i) determine the safe dose of CYT997 when given in combination with
carboplatin in patients with relapsed glioblastoma multiforme (glioma) and (ii) to determine
whether the combination of CYT997 with carboplatin is a useful treatment for glioma.
Trial website
https://clinicaltrials.gov/ct2/show/NCT00650949
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



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT00650949