- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00650949
Efficacy Study of CYT997 in Combination With Carboplatin in Glioblastoma
April 25, 2013 updated by: Gilead Sciences
A Phase Ib/II Study of CYT997 in Combination With Carboplatin in Relapsed Glioblastoma Multiforme
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.
Study Overview
Status
Terminated
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
20
Phase
- Phase 2
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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New South Wales
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St-Leonards, New South Wales, Australia, 2065
- Royal North Shore Hospital
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Queensland
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Southport, Queensland, Australia, 4215
- Gold Coast Hospital
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South Australia
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Bedford Park, South Australia, Australia, 5042
- Flinders Medical Centre
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Victoria
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Melbourne, Victoria, Australia, 3168
- Monash Medical Centre
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
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 Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: CYT997
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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
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
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
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Ongoing throughout therapy up until 30 days after last dose of CYT997
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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
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6 months after initiation of therapy
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Objective response rate (ORR)
Time Frame: Response is measured every second cycle of therapy
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Response is measured every second cycle of therapy
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Overall survival
Time Frame: Baseline to study completion
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Baseline to study completion
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Safety and tolerability
Time Frame: Measured continuously from study commencement through to 30 days after last dose of CYT997
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Measured continuously from study commencement through to 30 days after last dose of CYT997
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Effects on pharmacodynamic markers of vascular disruption and tumour apoptosis
Time Frame: Measured during first cycle of therapy
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Measured during first cycle of therapy
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Pharmacokinetic analysis of carboplatin and CYT997 in combination
Time Frame: Assessed during first cycle of therapy
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Assessed during first cycle of therapy
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Study Chair: Jason Lickliter, MD, Peninsula Health
- Principal Investigator: Helen Wheeler, MD, Royal North Shore Hospital
- Principal Investigator: Ganessan Kichenadasse, MD, Flinders Medical Centre
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
November 1, 2009
Primary Completion (Actual)
June 1, 2011
Study Completion (Actual)
June 1, 2011
Study Registration Dates
First Submitted
March 27, 2008
First Submitted That Met QC Criteria
March 31, 2008
First Posted (Estimate)
April 2, 2008
Study Record Updates
Last Update Posted (Estimate)
May 3, 2013
Last Update Submitted That Met QC Criteria
April 25, 2013
Last Verified
April 1, 2013
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- CCL08001
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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