Bevacizumab in Recurrent Grade II and III Glioma
- Conditions
- Central Nervous System Tumors
- Interventions
- Drug: TemozolomideBiological: Bevacizumab
- Registration Number
- NCT01164189
- Lead Sponsor
- European Organisation for Research and Treatment of Cancer - EORTC
- Brief Summary
RATIONALE: Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether temozolomide is more effective when given with or without bevacizumab in treating patients with recurrent glioma.
PURPOSE: This randomized clinical trial is studying how well temozolomide works with or without bevacizumab in treating patients with recurrent glioma.
- Detailed Description
OBJECTIVES:
Primary
* To document the activity of both combination temozolomide plus bevacizumab and temozolomide alone in patients with recurrent grade II or grade III glioma without 1p/19q co-deletion.
Secondary
* To characterize the safety of treatment in these patients.
* To document the quality of life and cognitive functioning, as a measure of clinical benefit, of these patients.
* To explore qualification or occurrence of prognostic and/or predictive biomarkers of activity or efficacy in these patients. (exploratory)
* To document the discordances between RANO and Macdonald's criteria for the evaluation of response and progression. (exploratory)
OUTLINE: This is a multicenter study. Patients are stratified according to institution, initial histology (grade II vs grade III), WHO performance status (0-1 vs 2), and prior treatment (radiotherapy \[RT\] alone, temozolomide \[TMZ\] or procarbazine, lomustine and vincristine \[PCV\] alone vs TMZ/RT). Patients are randomized to 1 of 2 treatment arms.
* Arm I: Patients receive oral temozolomide once daily on days 1-5. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.
* Arm II: Patients receive oral temozolomide as in arm I and bevacizumab IV over 90 minutes on days 1 and 15. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.
Patients complete neurocognitive questionnaires (i.e., the Hopkins Verbal Learning test, the Controlled Oral Word Association test, and the Trail Making tests A and B). Quality-of-life assessment questionnaires, including EORTC QLQ-C30 and EORTC-BN20, are completed by both patients and caregivers/relatives at baseline and then periodically.
Frozen tumor biopsies or paraffin blocks and blood specimens are collected for bio-banking and translational research.
After completion of study therapy, patients are followed up every 3 months.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 155
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Temozolomide Temozolomide Administered orally on day 1-5, 150-200 mg/m(2), repeated every 4 weeks, up to 12 cycles Temozolomide + Bevacizumab Bevacizumab TMZ: Administered orally on day 1-5, 150-200 mg/m(2), repeated every 4 weeks, up to 12 cycles Beva: 10 mg/kg bw IV in 90 minutes on day 1 and 14, 4 week cycles. Temozolomide + Bevacizumab Temozolomide TMZ: Administered orally on day 1-5, 150-200 mg/m(2), repeated every 4 weeks, up to 12 cycles Beva: 10 mg/kg bw IV in 90 minutes on day 1 and 14, 4 week cycles.
- Primary Outcome Measures
Name Time Method Probability of survival at 1 year From the date of randomization up to the date of death, assessed up to 12 months Patients alive at 12 months
- Secondary Outcome Measures
Name Time Method Steroid use At baseline and every 3 months untill lost to follow-up Objective response rate and duration of response From the date of randomization until disease progression Objective response includes best overall responses complete response and partial response
Progression-free survival From the date of randomization until the date of objective progression or the date of patient's death whichever occurs first Overall survival and survival at 24 months From the date of randomization up to the date of death Safety After the first ten patients in each arm have completed the first two cycles or have stopped treatment, an interim safety review of those patients will be conducted. Clinical/neurological deterioration-free survival From the date of randomization until the date of neurological deterioration Quality of life of patients and caregivers/relatives At baseline and every 3 months untill lost to follow-up Cognitive deterioration At baseline and every 3 months untill lost to follow-up
Trial Locations
- Locations (39)
U.Z. Leuven - Campus Gasthuisberg
🇧🇪Leuven, Belgium
Medical University Vienna - General Hospital AKH
🇦🇹Vienna, Austria
CHU Pitie-Salpetriere
🇫🇷Paris, France
Universitair Ziekenhuis Brussel
🇧🇪Brussel, Belgium
Landesnervenklinik Wagner Jauregg
🇦🇹Linz, Austria
CHRU de Lille
🇫🇷Lille, France
Assistance Publique - Hôpitaux de Marseille - Hôpital de La Timone
🇫🇷Marseille, France
CHU de Nice - Hopital Pasteur
🇫🇷Nice, France
Centre Hospitalier Universitaire Vaudois
🇨🇭Lausanne, Switzerland
Academisch Ziekenhuis Maastricht
🇳🇱Maastricht, Netherlands
Universitair Medisch Centrum - Academisch Ziekenhuis
🇳🇱Utrecht, Netherlands
Centre Eugene Marquis
🇫🇷Rennes, France
Ospedale Bellaria
🇮🇹Bologna, Italy
Universitaetsklinikum Bonn
🇩🇪Bonn, Germany
NHS Greater Glasgow and Clyde - Beatson West of Scotland Cancer Centre - Gartnavel General Hospital
🇬🇧Glasgow, United Kingdom
Institut Gustave Roussy
🇫🇷Paris, France
Institut de Cancerologie de l'Ouest (ICO) - Centre Rene Gauducheau
🇫🇷Saint - Herblain, France
Universitaetsklinikum - Essen
🇩🇪Essen, Germany
Klinikum Der J.W. Goethe Universitaet
🇩🇪Frankfurt am Main, Germany
Centre Paul Strauss
🇫🇷Strasbourg, France
UniversitaetsSpital Zurich - Division of Oncology
🇨🇭Zurich, Switzerland
Radboud University Nijmegen Medical Centre
🇳🇱Nijmegen, Netherlands
Daniel Den Hoed Cancer Center at Erasmus Medical Center
🇳🇱Rotterdam, Netherlands
Leeds Teaching Hospitals NHS Trust - St. James's University Hospital
🇬🇧Leeds, United Kingdom
Royal Marsden Hospital - Sutton, Surrey
🇬🇧Sutton, United Kingdom
University Hospitals Bristol NHS Foundation Trust - Bristol Haematology And Oncology Centre
🇬🇧Bristol, United Kingdom
University Of Dundee - Ninewells Hospital
🇬🇧Dundee, United Kingdom
Nottingham University Hospitals NHS Trust - City Hospital
🇬🇧Nottingham, United Kingdom
CHU de Lyon - CHU Lyon - Hopital neurologique Pierre Wertheimer
🇫🇷Lyon, France
University Medical Center Groningen
🇳🇱Groningen, Netherlands
Universitaetskliniken Regensburg
🇩🇪Regensburg, Germany
Medisch Centrum Haaglanden - Westeinde
🇳🇱Den Haag, Netherlands
Imperial College Healthcare NHS Trust - Charing Cross Hospital
🇬🇧London, United Kingdom
The Christie NHS Foundation Trust
🇬🇧Manchester, United Kingdom
University College Hospital
🇬🇧London, United Kingdom
Sheffield Teaching Hospitals NHS Foundation Trust - Weston Park Hospital
🇬🇧Sheffield, United Kingdom
NHS Lothian - Western General Hospital
🇬🇧Edinburgh, United Kingdom
Freeman Hospital, Northern Centre For Cancer Care
🇬🇧Newcastle upon Tyne, United Kingdom
Universitaetsklinikum Heidelberg - UniversitaetsKlinikum Heidelberg - Head Hospital
🇩🇪Heidelberg, Germany