Phase III Trial Exploring the Combination of Bevacizumab and Lomustine in Patients With First Recurrence of a Glioblastoma
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 592
- 试验地点
- 2
- 主要终点
- Overall Survival
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
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.
干预措施: bevacizumab (Biological)
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.
干预措施: lomustine (Drug)
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.
干预措施: DNA methylation analysis (Genetic)
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.
干预措施: laboratory biomarker analysis (Other)
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.
干预措施: cognitive assessment (Procedure)
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.
干预措施: quality-of-life assessment (Procedure)
Arm 2
Lomustine single agent 110 mg/m² every 6 weeks (cap. 200 mg) (at further progression treatment will be according to investigators discretion).
干预措施: lomustine (Drug)
Arm 2
Lomustine single agent 110 mg/m² every 6 weeks (cap. 200 mg) (at further progression treatment will be according to investigators discretion).
干预措施: DNA methylation analysis (Genetic)
Arm 2
Lomustine single agent 110 mg/m² every 6 weeks (cap. 200 mg) (at further progression treatment will be according to investigators discretion).
干预措施: laboratory biomarker analysis (Other)
Arm 2
Lomustine single agent 110 mg/m² every 6 weeks (cap. 200 mg) (at further progression treatment will be according to investigators discretion).
干预措施: cognitive assessment (Procedure)
Arm 2
Lomustine single agent 110 mg/m² every 6 weeks (cap. 200 mg) (at further progression treatment will be according to investigators discretion).
干预措施: quality-of-life assessment (Procedure)
结局指标
主要结局
Overall Survival
时间窗: Time to event
次要结局
- 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)
- CTCAE version 4.0. NYHA criteria will be used for assessing heart failure(Worst grade)
- 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)