Efficacy Study of CYT997 in Combination With Carboplatin in Glioblastoma

This study has been terminated.
(Strategic)
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT00650949
First received: March 27, 2008
Last updated: April 25, 2013
Last verified: April 2013
  Purpose

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.


Condition Intervention Phase
Glioblastoma Multiforme
Drug: CYT997
Drug: Carboplatin
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase Ib/II Study of CYT997 in Combination With Carboplatin in Relapsed Glioblastoma Multiforme

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

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 ]

Enrollment: 20
Study Start Date: November 2009
Study Completion Date: June 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CYT997 Drug: 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.
Drug: Carboplatin
Intravenous infusion over 1 hour at area under the concentration-time curve (AUC)=5 on Day 1 of a 21-day cycle

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00650949

Locations
Australia, New South Wales
Royal North Shore Hospital
St-Leonards, New South Wales, Australia, 2065
Australia, Queensland
Gold Coast Hospital
Southport, Queensland, Australia, 4215
Australia, South Australia
Flinders Medical Centre
Bedford Park, South Australia, Australia, 5042
Australia, Victoria
Monash Medical Centre
Melbourne, Victoria, Australia, 3168
Sponsors and Collaborators
Gilead Sciences
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
  More Information

No publications provided

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT00650949     History of Changes
Other Study ID Numbers: CCL08001
Study First Received: March 27, 2008
Last Updated: April 25, 2013
Health Authority: United States: Food and Drug Administration
Australia: Department of Health and Ageing Therapeutic Goods Administration

Keywords provided by Gilead Sciences:
Glioblastoma multiforme
Glioma
Phase Ib/II
CYT997

Additional relevant MeSH terms:
Glioblastoma
Astrocytoma
Glioma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Carboplatin
Antineoplastic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014