Efficacy Study of CYT997 in Combination With Carboplatin in Glioblastoma
This study has been terminated.
Information provided by (Responsible Party):
First received: March 27, 2008
Last updated: April 25, 2013
Last verified: April 2013
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.
||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
||A Phase Ib/II Study of CYT997 in Combination With Carboplatin in Relapsed Glioblastoma Multiforme
Primary Outcome Measures:
- Safety and tolerability of escalating doses of CYT997 when given in combination with standard carboplatin therapy (Phase Ib component) [ Time Frame: Ongoing throughout therapy up until 30 days after last dose of CYT997 ] [ Designated as safety issue: Yes ]
- 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) [ Time Frame: 6 months after initiation of therapy ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- Objective response rate (ORR) [ Time Frame: Response is measured every second cycle of therapy ] [ Designated as safety issue: No ]
- Overall survival [ Time Frame: Baseline to study completion ] [ Designated as safety issue: No ]
- Safety and tolerability [ Time Frame: Measured continuously from study commencement through to 30 days after last dose of CYT997 ] [ Designated as safety issue: Yes ]
- Effects on pharmacodynamic markers of vascular disruption and tumour apoptosis [ Time Frame: Measured during first cycle of therapy ] [ Designated as safety issue: No ]
- Pharmacokinetic analysis of carboplatin and CYT997 in combination [ Time Frame: Assessed during first cycle of therapy ] [ Designated as safety issue: No ]
| Study Start Date:
| Study Completion Date:
| Primary Completion Date:
||June 2011 (Final data collection date for primary outcome measure)
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.
Intravenous infusion over 1 hour at area under the concentration-time curve (AUC)=5 on Day 1 of a 21-day cycle
|Ages Eligible for Study:
||18 Years and older
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00650949
|Royal North Shore Hospital
|St-Leonards, New South Wales, Australia, 2065 |
|Gold Coast Hospital
|Southport, Queensland, Australia, 4215 |
|Flinders Medical Centre
|Bedford Park, South Australia, Australia, 5042 |
|Monash Medical Centre
|Melbourne, Victoria, Australia, 3168 |
||Jason Lickliter, MD
||Helen Wheeler, MD
||Royal North Shore Hospital
||Ganessan Kichenadasse, MD
||Flinders Medical Centre
No publications provided
History of Changes
|Other Study ID Numbers:
|Study First Received:
||March 27, 2008
||April 25, 2013
||United States: Food and Drug Administration
Australia: Department of Health and Ageing Therapeutic Goods Administration
Keywords provided by Gilead Sciences:
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on December 04, 2013
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue