A Study of Avastin (Bevacizumab) and Irinotecan Versus Temozolomide Radiochemistry in Patients With Glioblastoma
2015年10月20日 更新者：Hoffmann-La Roche
This 2 arm study will compare the effect of Avastin + irinotecan versus temozolomide, in combination with conventional involved field radiotherapy, in patients with newly diagnosed glioblastoma and a non-methylated MGMT promoter.
Patients will be randomized 3:1 to receive Avastin 10mg/kg iv every 2 weeks + irinotecan 125mg/m2 iv every 2 weeks, or temozolomide 75mg/m2 po daily during radiotherapy followed by 6 cycles of temozolomide 150-200mg/m2 po daily on days 1-5 of each 4 week cycle.
The anticipated time on study treatment is until disease progression, and the target sample size is 100-500 individuals.
研究概览
研究类型
介入性
注册 (实际的)
182
阶段
- 阶段2
联系人和位置
本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。
学习地点
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Aachen、德国、52074
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Berlin、德国、13353
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Bochum、德国、44892
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Bonn、德国、53127
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Chemnitz、德国、09113
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Dresden、德国、01307
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Düsseldorf、德国、40225
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Erfurt、德国、99089
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Erlangen、德国、91054
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Frankfurt am Main、德国、60528
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Freiburg、德国、79106
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Göttingen、德国、37075
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Idar-Oberstein、德国、55743
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Kiel、德国、24105
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Köln、德国、50937
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Leipzig、德国、04103
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Mannheim、德国、68167
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Marburg、德国、35043
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Muenchen、德国、81377
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München、德国、81675
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Münster、德国、48149
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Regensburg、德国、93053
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Tübingen、德国、72076
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Ulm、德国、89081
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参与标准
研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
18年 至 70年 (成人、年长者)
接受健康志愿者
不
有资格学习的性别
全部
描述
Inclusion Criteria:
- adult patients, 18-70 years of age;
- glioblastoma, confirmed histologically;
- no previous chemotherapy or radiotherapy for glioblastoma;
- non-methylated MGMT promoter in the tumor.
Exclusion Criteria:
- prior systemic treatment for glioblastoma multiforme;
- prior treatment with Avastin;
- significant cardiovascular disease;
- other active malignant disease.
学习计划
本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：随机化
- 介入模型：并行分配
- 屏蔽：无（打开标签）
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
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实验性的：1个
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10mg/kg iv every 2 weeks
125mg/m2 iv every 2 weeks
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有源比较器：2个
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75mg/m2 po daily during radiotherapy, followed by 150-200mg/m2/day po on days 1-5 of each 6x4 week cycle of adjuvant therapy
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研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Percentage of Participants Achieving Progression-Free Survival (PFS) Without Disease Progression or Death at 6 Months
大体时间：6 months
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Progression-free survival was defined as the time from randomization to objective tumor progression or death from any cause, whichever came first.
Progression was defined as 25 percent (%) increase in size of enhancing tumor or any new tumor on gadolinium contrast agent magnetic resonance imaging (Gd-MRI) scans, or neurologically worse, and steroids stable or increased.
Percentage of participants achieving PFS without disease progression or death was reported.
|
6 months
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Progression-Free Survival (PFS)
大体时间：From baseline to the end of the study (up to 4.5 years)
|
Progression-free survival was defined as the time from randomization to objective tumor progression or death from any cause, whichever came first.
Progression was defined as 25% increase in size of enhancing tumor or any new tumor on Gd-MRI scans, or neurologically worse, and steroids stable or increased.
PFS was estimated using Kaplan-Meier method.
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From baseline to the end of the study (up to 4.5 years)
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Overall Survival (OS)
大体时间：From baseline until death (up to 4.5 years)
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Overall survival was defined as the time from randomization to death from any cause.
OS was estimated using Kaplan-Meier method.
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From baseline until death (up to 4.5 years)
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Percentage of Participants Who Discontinued
大体时间：From baseline until death (up to 4.5 years)
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Discontinuation was defined as the percentage of participants who permanently discontinued treatment in either treatment arm.
Percentage of participant with individual discontinuation reason are reported.
CNS: central nervous system; CTCAE: Common Terminology Criteria for Adverse Events .
Other reason refers to any other reason than the specified ones.
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From baseline until death (up to 4.5 years)
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Number of Participants With A Best Overall Response (BOR) of Complete Response (CR) and With A BOR of CR or Partial Response (PR)
大体时间：4 week after radiotherapy (RT) (up to Week 4), >4 Week after RT (up to Week 8) and Month 6
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BOR was defined as the best response observed for a participant during assessment.
Number of participants who had BOR as CR and number of participants who had BOR as CR or PR were reported.
Complete response was defined as disappearance of all enhancing tumor on consecutive Gd-MRI scans at least 1 month apart, off steroids, and neurologically stable or improved.
Partial response was defined as 50% reduction in size of enhancing tumor on consecutive Gd-MRI scans at least 1 month apart, steroids stable or reduced, and neurologically stable or improved.
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4 week after radiotherapy (RT) (up to Week 4), >4 Week after RT (up to Week 8) and Month 6
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Percentage of Participants With Response on FLAIR Imaging
大体时间：At screening, Baseline, Month 6 and Therapy Discontinuation (Up to 4.5 years)
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FLAIR lesions were determined as "stable", "progressive" or "decreased". FLAIR lesions was determined as "progressive" only if they were not be attributed to causes apart from tumor infiltration (sequelae of radiation therapy, demyelination, ischemia, infection, seizures, or other treatment effects). Percentage of participants are based on ITT population. Dis.=Discontinuation. |
At screening, Baseline, Month 6 and Therapy Discontinuation (Up to 4.5 years)
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Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ - C30) at Baseline, Post-Baseline (up to Month 30)
大体时间：Baseline, Post-Baseline (up to Month 30)
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The EORTC QLQ-C30 incorporates: 5 functional scales (physical, role, cognitive, emotional, and social); 9 symptom scales (fatigue, pain, nausea and vomiting, dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties); and a global health and quality-of-life scale.
Most questions used 4 point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale (1 'very poor' to 7 'Excellent').
Scores were averaged and transformed to 0-100 scale; higher score for Global Qol/functional scales=better level of functioning or a higher score for symptom scale=greater degree of symptoms.
The change in global health status was determined to be the difference in values at baseline and each specific visit.
The term ''baseline'' refers to the time of randomization to the maintenance phase.
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Baseline, Post-Baseline (up to Month 30)
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Change From Baseline for EORTC QLQ Brain Neoplasm 20 (BN20) at Baseline, Post-Baseline (up to Month 30)
大体时间：Baseline, Post-Baseline (up to Month 30)
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EORTC QLQ-BN20 consisted of 20 items assessing visual disorders, motor dysfunction, communication deficit, various disease symptoms (e.g.
headaches and seizures), treatment toxicities (e.g.
hair loss) and future uncertainty.
All of the 20 items are rated on a 4 point Likert scale from 1=not at all, 2=a little, 3=quite a bit and 4=very much, and were linearly transformed to a 0-100 scale, with higher scores indicating more severe symptoms.
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Baseline, Post-Baseline (up to Month 30)
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Change From Baseline for Mini-Mental Status Examination (MMSE) at Baseline, Post-Baseline (up to Month 30)
大体时间：Baseline, Post-Baseline (up to Month 30)
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The MMSE briefly measures orientation to time and place, immediate recall, short-term verbal memory, calculation, language and construct ability.
Each area tested had a designated point value, the total score can range from 0 to 30, with a higher score indicating better function.
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Baseline, Post-Baseline (up to Month 30)
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Change From Baseline for Karnofsky Performance Status (KPS) Score at Baseline, Post-Baseline (up to Month 30)
大体时间：Baseline, Post-Baseline (up to Month 30)
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KPS is an 11-level score (0, 10, 20, 30, 40, 50, 60, 70, 80, 90, and 100) which ranges between 0 (death) to 100 (complete healthy status); a higher score represents a higher ability to perform daily tasks.
Deterioration in KPS was defined as decrease of 20 or more points in KPS score.
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Baseline, Post-Baseline (up to Month 30)
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Percentage of Participants Who Received Corticosteroid for Glioblastoma
大体时间：From baseline to Month 6
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Participants used corticosteroids for the glioblastoma condition.
Corticosteroids included dexamethasone, methylprednisone, fortecortin, hydrocortisone, urbason, and prednisolone.
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From baseline to Month 6
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Time to Treatment Failure
大体时间：From baseline until end of study (up to 4.5 years)
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From baseline until end of study (up to 4.5 years)
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合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
出版物和有用的链接
负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。
一般刊物
- Schafer N, Proescholdt M, Steinbach JP, Weyerbrock A, Hau P, Grauer O, Goldbrunner R, Friedrich F, Rohde V, Ringel F, Schlegel U, Sabel M, Ronellenfitsch MW, Uhl M, Grau S, Hanel M, Schnell O, Krex D, Vajkoczy P, Tabatabai G, Mack F, Schaub C, Tzaridis T, Niessen M, Kebir S, Leutgeb B, Urbach H, Belka C, Stummer W, Glas M, Herrlinger U. Quality of life in the GLARIUS trial randomizing bevacizumab/irinotecan versus temozolomide in newly diagnosed, MGMT-nonmethylated glioblastoma. Neuro Oncol. 2018 Jun 18;20(7):975-985. doi: 10.1093/neuonc/nox204.
- Herrlinger U, Schafer N, Steinbach JP, Weyerbrock A, Hau P, Goldbrunner R, Friedrich F, Rohde V, Ringel F, Schlegel U, Sabel M, Ronellenfitsch MW, Uhl M, Maciaczyk J, Grau S, Schnell O, Hanel M, Krex D, Vajkoczy P, Gerlach R, Kortmann RD, Mehdorn M, Tuttenberg J, Mayer-Steinacker R, Fietkau R, Brehmer S, Mack F, Stuplich M, Kebir S, Kohnen R, Dunkl E, Leutgeb B, Proescholdt M, Pietsch T, Urbach H, Belka C, Stummer W, Glas M. Bevacizumab Plus Irinotecan Versus Temozolomide in Newly Diagnosed O6-Methylguanine-DNA Methyltransferase Nonmethylated Glioblastoma: The Randomized GLARIUS Trial. J Clin Oncol. 2016 May 10;34(14):1611-9. doi: 10.1200/JCO.2015.63.4691. Epub 2016 Mar 14.
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始
2010年6月1日
初级完成 (实际的)
2014年9月1日
研究完成 (实际的)
2014年9月1日
研究注册日期
首次提交
2009年6月16日
首先提交符合 QC 标准的
2009年8月26日
首次发布 (估计)
2009年8月27日
研究记录更新
最后更新发布 (估计)
2015年11月20日
上次提交的符合 QC 标准的更新
2015年10月20日
最后验证
2015年10月1日
更多信息
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.