今天是:2019-01-16 星期三

阿帕替尼联合替莫唑胺治疗成人初次复发的原发胶质母细胞瘤的多中心开放随机对照研究
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注册号:

Registration number:

ChiCTR1900020646 

最近更新日期:

Date of Last Refreshed on:

2019-01-11 

注册时间:

Date of Registration:

2019-01-11 

注册号状态:

预注册  

Registration Status:

Prospective registration  

注册题目:

阿帕替尼联合替莫唑胺治疗成人初次复发的原发胶质母细胞瘤的多中心开放随机对照研究 

Public title:

A multicenter open-label randomized controlled trial for apatinib combined with temozolomide in adult primary glioblastoma at first recurrence 

注册题目简写:

 

English Acronym:

 

研究课题的正式科学名称:

阿帕替尼联合替莫唑胺治疗成人初次复发的原发胶质母细胞瘤的多中心开放随机对照研究 

Scientific title:

A multicenter open-label randomized controlled trial for apatinib combined with temozolomide in adult primary glioblastoma at first recurrence 

研究课题代号(代码):

Study subject ID:

 

在二级注册机构或其它机构的注册号:

The registration number of the Partner Registry or other register:

 

申请注册联系人:

张俊平 

研究负责人:

张俊平 

Applicant:

Jun-ping Zhang 

Study leader:

Jun-ping Zhang 

申请注册联系人电话:

Applicant telephone:

+86 010 62856783 

研究负责人电话:

Study leader's telephone:

+86 010 62856783 

申请注册联系人传真 :

Applicant Fax:

 

研究负责人传真:

Study leader's fax:

 

申请注册联系人电子邮件:

Applicant E-mail:

doczhjp@hotmail.com 

研究负责人电子邮件:

Study leader's E-mail:

doczhjp@hotmail.com 

申请单位网址(自愿提供):

Applicant website(voluntary supply):

 

研究负责人网址(自愿提供):

Study leader's website(voluntary supply):

 

申请注册联系人通讯地址:

北京市海淀区香山一棵松50号 

研究负责人通讯地址:

北京市海淀区香山一棵松50号 

Applicant address:

50 Yi-Ke-Song Road, Haidian District, Beijing, China 

Study leader's address:

50 Yi-Ke-Song Road, Haidian District, Beijing, China 

申请注册联系人邮政编码:

Applicant postcode:

 

研究负责人邮政编码:

Study leader's postcode:

 

申请人所在单位:

首都医科大学三博脑科医院 

Applicant's institution:

Sanbo Brain Hospital, Capital Medical University 

是否获伦理委员会批准:

是 

Approved by ethic committee:

Yes 

伦理委员会批件文号:

Approved No. of ethic committee:

SBNK-2018-046-01 

伦理委员会批件附件:

Approved file of Ethical Committee:

批准本研究的伦理委员会名称:

首都医科大学三博脑科医院伦理委员会 

Name of the ethic committee:

Ethics Committee of Sanbo Brain Hospital, Capital Medical University 

伦理委员会批准日期:

Date of approved by ethic committee:

 

伦理委员会联系人:

李耕子 

Contact Name of the ethic committee:

Geng-zi Li 

伦理委员会联系地址:

北京市海淀区香山一棵松50号 

Contact Address of the ethic committee:

50 Yi-Ke-Song Road, Haidian District, Beijing, China 

伦理委员会联系人电话:

Contact phone of the ethic committee:

 

伦理委员会联系人邮箱:

Contact email of the ethic committee:

 

研究实施负责(组长)单位:

首都医科大学三博脑科医院 

Primary sponsor:

Sanbo Brain Hospital, Capital Medical University 

研究实施负责(组长)单位地址:

北京市海淀区香山一棵松50号 

Primary sponsor's address:

50 Yi-Ke-Song Road, Haidian District, Beijing, China 

试验主办单位(项目批准或申办者):

Secondary sponsor:

国家:

中国

省(直辖市):

北京

市(区县):

Country:

China

Province:

Beijing

City:

单位(医院):

首都医科大学三博脑科医院

具体地址:

北京市海淀区香山一棵松50号

Institution
hospital:

Sanbo Brain Hospital, Capital Medical University

Address:

50 Yi-Ke-Song Road, Haidian District, Beijing, China

经费或物资来源:

江苏恒瑞医药股份有限公司 

Source(s) of funding:

Jiangsu Hengrui Pharmaceutical Co., Ltd.  

研究疾病:

复发胶质母细胞瘤 

Target disease:

Recurrent glioblastoma 

研究疾病代码:

 

Target disease code:

 

研究类型:

干预性研究 

Study type:

Interventional study 

研究所处阶段:

上市后药物 

Study phase:

Post-market 

研究目的:

评价阿帕替尼联合替莫唑胺治疗成人初次复发的原发胶质母细胞瘤的有效性和安全性。 

Objectives of Study:

To evaluate the effect and safety of apatinib combined with temozolomide in adult primary glioblastoma at first recurrence. 

药物成份或治疗方案详述:

 

Description for medicine or protocol of treatment in detail:

 

研究设计:

随机平行对照试验 

Study design:

Randomized parallel controlled trial 

纳入标准:

1. 年龄18岁~70岁,男女不限。 2. 幕上占位,经活检或手术,初次术后病理诊断为胶质母细胞瘤。 3. 术后接受放疗,距离末次放疗时间间隔≥3个月。 4. 术后接受不超过1个化疗方案的化疗,且距离末次化疗时间间隔≥4周。 5. 经MRI证实肿瘤存在明确复发,增强灶直径≥1cm,≥2个层面(层间距5mm),或经过再次活检或手术,病理证实为复发。 6. 距离末次活检或手术时间间隔≥2周。 7. KPS评分≥60%。 8. 如果患者正在使用糖皮质激素治疗,在基线MRI之前至少5天内激素用量稳定或减少。 9. 预计生存期≥12周。 10. 主要脏器功能正常,无严重血液、心、肺、肝、肾功能异常和免疫缺陷疾病。实验室检查符合下列要求: (1)血常规检查, 需符合(14天内未输血): a. HGB≥110g/L; b. WBC≥3.0×109/L;NEUT≥1.5×109/L; c. PLT ≥75×109/L; (2)生化检查需符合以下标准: a. BIL≤1.5倍正常值上限(ULN); b. ALT和AST≤2.0×ULN; c. 血清Cr≤1.5×ULN或内生肌酐清除率≥50ml/min(Cockcroft-Gault公式); (3)便潜血(-); (4)尿常规正常,或尿蛋白<(++),或24小时尿蛋白量<1.0 g; (5)左室射血分数(LVEF)≥50%。 11. 凝血功能正常,无活动性出血和血栓形成疾病。 a. 国际标准化比值INR≤1.5×ULN; b. 部分凝血活酶时间APTT≤1.5×ULN; c. 凝血酶原时间PT≤1.5ULN。 12. 育龄妇女须在入组前7天内进行妊娠试验(血清或尿液)结果为阴性,且自愿在观察期间和末次给予甲磺酸阿帕替尼片后8周内采用适当的方法避孕;对于男性,应为手术绝育或同意在观察期间和末次给予甲磺酸阿帕替尼片后8周内采用适当方法避孕。 13. 提供末次活检或手术后肿瘤组织切片25-30张。 14. 患者自愿加入本研究,并且签署知情同意书(ICF)。 15. 预计依从性好者,能按方案要求随访疗效及不良反应。 

Inclusion criteria

1. Age 18-70 years old, male or female; 2. Primary supratentorial glioblastoma was pathologically diagnosed after first biopsy or resection; 3. Radiotherapy after surgery was needed, and the time interval between the last radiotherapy and enrollment is no less than 3 months; 4. No more than 1 chemotherapy regimen was accepted, and the time interval from the last chemotherapy was no less than 4 weeks; 5. Recurrence was confirmed by MRI, the diameter of the enhanced lesion is greater than or equal to 1cm, greater than or equal to 2 layers (the interval between layers is 5mm), or confirmed pathologically after another biopsy or surgery; 6. The interval from the last biopsy or surgery should be no less than 2 weeks; 7. KPS score should be at least 60%; 8. If the patient is on glucocorticoid therapy, hormone dosage should be stable or decreased at least 5 days prior to baseline MRI; 9. Life expectancy is no less than 12 weeks; 10. The main organs function is normal, without serious blood, heart, lung, liver, kidney function abnormalities or immunodeficiency diseases.Laboratory inspection meets the following requirements: (1) blood routine examination should be in line with (no blood transfusion within 14 days): HGB 110 g/L or higher; the WBC acuity 3.0 x 10^9/L; NEUT acuity 1.5 x 10^9/L; PLT acuity 75 x 109 / L; (2) biochemical examination should meet the following standards: A. BIL is less than or equal to 1.5 times upper limit of normal value (ULN); B. ALT and AST are less than or equal to 2.0 times ULN; C. Serum Cr less than or equal to 1.5 x ULN or endogenous creatinine clearance rate greater than or equal to 50ml/min (Cockcroft-Gault formula); (3) fecal occult blood (-); (4) normal urine routine, or urine protein <(++), or 24 hours of urine protein < 1.0g; (5) LVEF should be greater than 50%; 11. Normal coagulation function, no active bleeding and thrombosis: (1) The international standardized ratio INR is less than or equal to 1.5 x ULN; (2) APTT is less than or equal to 1.5 x ULN; (3) PT is less than or equal to 1.5uln; 12. Women of child-bearing age shall undergo a pregnancy test (serum or urine) with negative results within 7 days prior to enrollment and shall voluntarily use appropriate contraceptive methods during the observation period and within 8 weeks after the last administration of apatinib mesylate tablets; For men, surgical sterilization or consent to appropriate contraceptive methods should be given during the observation period and within 8 weeks of the last administration of apatinib mesylate tablets; 13. Provide 25-30 slides of tumor tissue of the last biopsy or surgery; 14. Patients volunteered to participate in the study and signed an informed consent form (ICF); 15. Good compliance is expected, and efficacy and adverse reactions can be followed up as required by the program.^ 

排除标准:

1. 既往应用抗肿瘤血管生成药物者; 2. 已知的对甲磺酸阿帕替尼任何成分过敏者; 3. 正在使用诱导肝药酶的抗癫痫药,除非已经更换为非肝药酶的抗癫痫药距离入组时至少2周; 4. 伴有其它恶性肿瘤者,除非已经无进展生存5年并且研究者认为复发风险低或原位癌患者; 5. 患有高血压病,经降压药物治疗无法降至正常范围者(收缩压≤140 mmHg / 舒张压≤ 90 mmHg); 6. 患有≥2级的冠心病、心律失常(包括QTc间期延长男性>450 ms,女性>470 ms)及心功能不全者; 7. 尿常规提示尿蛋白≥(++),或24小时尿蛋白量≥1.0g; 8. 凝血功能异常(INR>1.5或凝血酶原时间(PT)>ULN+4秒或APTT >1.5×ULN),具有出血倾向或正在接受溶栓或抗凝治疗; 9. 具有影响口服药物吸收的多种因素,如恶心呕吐、慢性腹泻和肠梗阻等; 10.入组前3个月内出现过显著临床意义的出血症状或具有明确的出血倾向,如消化道出血、出血性胃溃疡、胃肠穿孔、基线期大便潜血++及以上,瘤内或颅内出血,或患有脉管炎等; 11.入组前12个月内发生的动/静脉血栓事件,如脑血管意外(包括暂时性缺血性发作、脑出血、脑梗塞)、深静脉血栓及肺栓塞等; 12. 怀孕或哺乳期妇女;有生育能力的患者不愿或无法采取有效的避孕措施者; 13. 研究者认为不适合纳入的其他情况。 

Exclusion criteria:

1. Previous treatment with anti-angiogenic drugs; 2. Persons who are known to be allergic to apatinib mesylate in any composition; 3. Receiving enzyme-inducing antiepileptic drugs (EIAEDs), unless the drugs have been replaced with non-EIAEDs for at least 2 weeks away from enrollment; 4. Patients with other malignant tumors, unless they have lived without progression for 5 years and the researchers believe that the risk of recurrence is low or the tumor is carcinoma in situ; 5. Patients with hypertension who cannot be reduced to normal by antihypertensive drug therapy (systolic blood pressure < 140 mmHg/diastolic blood pressure < 90 mmHg); 6. Coronary heart disease, arrhythmia (including prolonged QTc interval > 450ms in men, > 470ms in women) and cardiac insufficiency with grade 2 or higher; 7. Urine routine indicated that urine protein was greater than or equal to (++), or urine protein was greater than or equal to 1.0g within 24 hours; 8. Abnormal coagulation function (INR >1.5 or prothrombin time (PT) > ULN+4 seconds or APTT >1.5 × ULN), with bleeding tendency or receiving thrombolytic or anticoagulant treatment; 9. Has a variety of factors affecting oral drug absorption, such as nausea and vomiting, chronic diarrhea and intestinal obstruction; 10. There were clinically significant bleeding symptoms or clear bleeding tendency within 3 months before enrollment, such as gastrointestinal bleeding, hemorrhagic gastric ulcer, gastrointestinal perforation, baseline fecal occult blood ++ or above, intracranial or intracranial hemorrhage, or vasculitis; 11. Arteriovenous thrombosis events occurred within 12 months before enrollment, such as cerebrovascular accidents (including temporary ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism, etc.; 12. Women who are pregnant or breast-feeding;Patients with fertility are unwilling or unable to take effective contraceptive measures; 13. Other conditions considered by the researchers to be inappropriate for inclusion. 

研究实施时间:

Study execute time:

From2019-02-01To 2022-01-31 

干预措施:

Interventions:

组别:

治疗组

样本量:

98

Group:

Group 1

Sample size:

干预措施:

阿帕替尼联合替莫唑胺治疗

干预措施代码:

Intervention:

Apatinib combined with temozolamide for treatment

Intervention code:

组别:

对照组

样本量:

49

Group:

Group 2

Sample size:

干预措施:

给予替莫唑胺治疗

干预措施代码:

Intervention:

The patients were treated with temozolomide

Intervention code:

研究实施地点:

Countries of recruitment and research settings:

国家:

中国 

省(直辖市):

北京 

市(区县):

 

Country:

China 

Province:

Beijing 

City:

 

单位(医院):

首都医科大学三博脑科医院 

单位级别:

三级甲等 

Institution
hospital:

Sanbo Brain Hospital, Capital Medical University  

Level of the institution:

Tertiary A Hospital 

测量指标:

Outcomes:

指标中文名:

6个月肿瘤无进展生存率

指标类型:

主要指标 

Outcome:

PFS-6%

Type:

Primary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

采集人体标本:

Collecting sample(s)
from participants:

标本中文名:

血液

组织:

Sample Name:

blood

Tissue:

人体标本去向

使用后销毁 

说明

Fate of sample:

Destruction after use 

Note:

征募研究对象情况:

Recruiting status:

尚未开始

Not yet recruiting

年龄范围:

Participant age:

最小 Min age 18 years
最大 Max age 70 years

性别:

男女均可

Gender:

Both

随机方法(请说明由何人用什么方法产生随机序列):

随机数字表

Randomization Procedure (please state who generates the random number sequence and by what method):

Random number table

盲法:

未说明

Blinding:

Not stated

原始数据公开时间:

The time of sharing IPD:

试验完成后6个月内公开/Within six months after the trial complete

共享原始数据的方式(说明:请填入公开原始数据日期和方式,如采用网络平台,需填该网络平台名称和网址):

暂无

The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url):

not yet

数据采集和管理(说明:数据采集和管理由两部分组成,一为病例记录表(Case Record Form, CRF),二为电子采集和管理系统(Electronic Data Capture, EDC),如ResMan即为一种基于互联网的EDC:

数据采集

Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture:

Case Record Form, CRF

数据管理委员会:

Data Managemen Committee:

有/Yes

注册人:

Name of Registration:

 2019-01-11
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