Bevacizumab and Lomustine for Recurrent GBM
- Conditions
- Glioblastoma MultiformeCognition DisordersDisability Evaluation
- Interventions
- Biological: bevacizumabGenetic: DNA methylation analysisOther: laboratory biomarker analysisProcedure: cognitive assessmentProcedure: quality-of-life assessment
- Registration Number
- NCT01290939
- Brief Summary
RATIONALE: 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. Drugs used in chemotherapy, such as lomustine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known which regimen of bevacizumab given together with lomustine is most effective in treating patients with glioblastoma multiforme in first recurrence.
PURPOSE: The primary objective of this study is to investigate whether the addition of bevacizumab to lomustine improves overall survival (OS) in patients with recurrent glioblastoma compared to treatment with lomustine alone.
- Detailed Description
OBJECTIVES:
* To determine the therapeutic role of bevacizumab as well as the most favorable approach to treatment optimization for sequencing the combination of bevacizumab and lomustine in patients with glioblastoma multiforme in first recurrence.
OUTLINE: This is a multicenter study. Patients are stratified according to institution, WHO performance status (0 vs \> 0), steroid administration (yes vs no), and largest diameter of tumor (≤ 40 mm vs \> 40 mm). Patients are randomized at 2:1 ratio to 1 of 2 treatment arms.
* Arm 1: Lomustine 90 mg/m² every 6 weeks (cap. 160 mg) + bevacizumab 10 mg/kg every 2 weeks (at further progression treatment will be according to investigators discretion). In the absence of hematological toxicity \> grade 1 during the first cycle the dose of lomustine can be escalated to 110 mg/m² (cap 200 mg) in their second cycle.
* Arm 2 (control arm): Lomustine single agent 110 mg/m² every 6 weeks (cap. 200 mg) (at further progression treatment will be according to investigators discretion).
One cycle will be defined arbitrarily (due to the lomustine sequencing) as 6 weeks for all arms. Day 1 of a cycle will be the first day when medication is taken.
Previously collected blood and tumor tissue samples are analyzed for MGMT methylation status, isocitrate dehydrogenase 1, and biomarkers of the VEGF pathway.
Patients and their caregivers/relatives complete quality-of-life questionnaires (EORTC QLQ-C30 and EORTC-BN20) at baseline, at 12 weeks, and then every 12 weeks after completion of study therapy. Patients also undergo neurocognitive assessment at baseline, at 12 weeks, and then every 12 weeks after completion of study therapy.
After completion of study treatment, patients are followed every 12 weeks.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 592
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 1 bevacizumab Lomustine 90 mg/m² every 6 weeks (cap. 160 mg) + bevacizumab 10 mg/kg every 2 weeks (at further progression treatment will be according to investigators discretion). In the absence of hematological toxicity \> grade 1 during the first cycle the dose of lomustine can be escalated to 110 mg/m² (cap 200 mg) in their second cycle. Arm 1 laboratory biomarker analysis Lomustine 90 mg/m² every 6 weeks (cap. 160 mg) + bevacizumab 10 mg/kg every 2 weeks (at further progression treatment will be according to investigators discretion). In the absence of hematological toxicity \> grade 1 during the first cycle the dose of lomustine can be escalated to 110 mg/m² (cap 200 mg) in their second cycle. Arm 1 cognitive assessment Lomustine 90 mg/m² every 6 weeks (cap. 160 mg) + bevacizumab 10 mg/kg every 2 weeks (at further progression treatment will be according to investigators discretion). In the absence of hematological toxicity \> grade 1 during the first cycle the dose of lomustine can be escalated to 110 mg/m² (cap 200 mg) in their second cycle. Arm 2 DNA methylation analysis Lomustine single agent 110 mg/m² every 6 weeks (cap. 200 mg) (at further progression treatment will be according to investigators discretion). Arm 2 laboratory biomarker analysis Lomustine single agent 110 mg/m² every 6 weeks (cap. 200 mg) (at further progression treatment will be according to investigators discretion). Arm 2 cognitive assessment Lomustine single agent 110 mg/m² every 6 weeks (cap. 200 mg) (at further progression treatment will be according to investigators discretion). Arm 2 quality-of-life assessment Lomustine single agent 110 mg/m² every 6 weeks (cap. 200 mg) (at further progression treatment will be according to investigators discretion). Arm 1 DNA methylation analysis Lomustine 90 mg/m² every 6 weeks (cap. 160 mg) + bevacizumab 10 mg/kg every 2 weeks (at further progression treatment will be according to investigators discretion). In the absence of hematological toxicity \> grade 1 during the first cycle the dose of lomustine can be escalated to 110 mg/m² (cap 200 mg) in their second cycle. Arm 1 quality-of-life assessment Lomustine 90 mg/m² every 6 weeks (cap. 160 mg) + bevacizumab 10 mg/kg every 2 weeks (at further progression treatment will be according to investigators discretion). In the absence of hematological toxicity \> grade 1 during the first cycle the dose of lomustine can be escalated to 110 mg/m² (cap 200 mg) in their second cycle. Arm 1 lomustine Lomustine 90 mg/m² every 6 weeks (cap. 160 mg) + bevacizumab 10 mg/kg every 2 weeks (at further progression treatment will be according to investigators discretion). In the absence of hematological toxicity \> grade 1 during the first cycle the dose of lomustine can be escalated to 110 mg/m² (cap 200 mg) in their second cycle. Arm 2 lomustine Lomustine single agent 110 mg/m² every 6 weeks (cap. 200 mg) (at further progression treatment will be according to investigators discretion).
- Primary Outcome Measures
Name Time Method Overall Survival Time to event
- Secondary Outcome Measures
Name Time Method CTCAE version 4.0. NYHA criteria will be used for assessing heart failure Worst grade PFS (RANO criteria), median , PFS 6 mo and PFS 12 mo, Overall survival: OS 9,12,24 mo time to event or fixed time points Response rate, duration of response and progression pattern time to event and fixed time points Patient-oriented criteria: clinical/neurological deterioration free survival, steroid use, quality of life (reported by patients and caregivers/relatives) and development of cognitive deterioration. 9,12,24 mo Molecular basis of gliomas and the identification of biomarkers to translate into advances in screening, diagnosis, treatment, and monitoring with improved clinical outcomes 9,12,24mo
Trial Locations
- Locations (2)
Erasmus MC - Daniel den Hoed Cancer Center
🇳🇱Rotterdam, Netherlands
Medisch Centrum Haaglanden - Westeinde
🇳🇱Den Haag, Netherlands