ChiCTR2000040116 版本V1.2 版本创建时间2020/11/21 05:00:56 中国临床试验注册中心

审核状态：

Project audit state：

通过审核

Successful

注册号：

Registration number：

 ChiCTR2000040116 

最近更新日期：

Date of Last Refreshed on：

 2020-11-21 04:57:30 

注册时间：

Date of Registration：

 2020-11-21 00:00:00 

注册号状态：

补注册

Registration Status：

Retrospective registration

注册题目：

安罗替尼联合放疗治疗MGMT阴性新诊断胶质母细胞瘤的前瞻性、单臂II期临床研究

Public title：

Prospective, single arm phase II clinical study of amlotinib combined with radiotherapy in the treatment of newly diagnosed MGMT negative glioblastoma

注册题目简写：

English Acronym：

研究课题的正式科学名称：

安罗替尼联合放疗治疗MGMT阴性新诊断胶质母细胞瘤的前瞻性、单臂II期临床研究

Scientific title：

Prospective, single arm phase II clinical study of amlotinib combined with radiotherapy in the treatment of newly diagnosed MGMT negative glioblastoma

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：

洪晓华 

研究负责人：

杨坤禹 

Applicant：

Hong Xiaohua 

Study leader：

Yang Kunyu 

申请注册联系人电话：

Applicant telephone：

 +86 13886130223

研究负责人电话：

Study leader's
telephone：

+86 13995595360

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：

 hongxiaohua008@163.com

研究负责人电子邮件：

Study leader's E-mail：

 Yangky71@aliyun.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：

湖北省武汉市解放大道1277号

研究负责人通讯地址：

湖北省武汉市解放大道1277号

Applicant address：

1277 Jiefang Avenue, Wuhan, Hubei, China

Study leader's address：

1277 Jiefang Avenue, Wuhan, Hubei, 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：

华中科技大学同济医学院附属协和医院

Applicant's institution：

Union Medical College Affiliated Hospital of Tongji Medical College, Huazhong University of science and technology

研究负责人所在单位：

华中科技大学同济医学院附属协和医院

Affiliation of the Leader：

Union Medical College Affiliated Hospital of Tongji Medical College, Huazhong University of science and technology

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：

 2020伦理字0390号

伦理委员会批件附件：

Approved file of Ethical Committee：

 查看附件View

批准本研究的伦理委员会名称：

华中科技大学同济医学院附属协和医院医学伦理委员会

Name of the ethic committee：

Medical ethics committee of Union Medical College Affiliated to Tongji Medical College of Huazhong University of science and technology

伦理委员会批准日期：

Date of approved by ethic committee：

 2020-08-06 00:00:00

伦理委员会联系人：

褚圆圆

Contact Name of the ethic committee：

Chu Yuanyuan

伦理委员会联系地址：

湖北省武汉市解放大道1277号

Contact Address of the ethic committee：

1277 Jiefang Avenue, Wuhan, Hubei, China

伦理委员会联系人电话：

Contact phone of the ethic committee：

 +86 15623939685

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：

华中科技大学同济医学院附属协和医院肿瘤中心

Primary sponsor：

Cancer center of Union Medical College Affiliated to Huazhong University of science and technology

研究实施负责（组长）单位地址：

湖北省武汉市解放大道1277号

Primary sponsor's address：

1277 Jiefang Avenue, Wuhan, Hubei, 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)：

湖北省

市(区县)：

Country：

China

Province：

Hubei

City：

单位(医院)：

华中科技大学同济医学院附属协和医院

具体地址：

湖北省武汉市解放大道1277号

Institution
hospital：

Union Medical College Affiliated Hospital of Tongji Medical College, Huazhong University of science and technology

Address：

1277 Jiefang Avenue, Wuhan

经费或物资来源：

无

Source(s) of funding：

no

研究疾病：

脑胶质瘤  

Target disease：

Brain stromal tumor

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：

 探索性研究/预试验 

Study phase：

0

研究设计：

单臂 

Study design：

Single arm 

研究目的：

评价安罗替尼同步放疗，随后6个周期安罗替尼辅助治疗治疗新诊断MGMT启动子甲基化阴性的GBM患者的总生存时间（OS）；评价安罗替尼同步放疗，随后6个周期安罗替尼辅助治疗治疗新诊断MGMT启动子甲基化阴性的GBM患者的无疾病生存时间（DFS）；  

Objectives of Study：

Objective to evaluate the overall survival time (OS) and disease-free survival (DFS) of patients with newly diagnosed MGMT promoter methylation negative GBM treated with amlotinib concurrent radiotherapy followed by 6 cycles of amlotinib adjuvant therapy;

药物成份或治疗方案详述：

 

Description for medicine or protocol of treatment in detail：

 

纳入标准：

1、年龄18-70岁，性别不限；
2、组织学诊断为脑胶质母细胞瘤，WHO分级为 IV级；
3、脑胶质母细胞瘤手术治疗后；
4、PCR法或NGS判定MGMT启动子甲基化阴性；
5、既往没有接受针对脑胶质母细胞瘤的除手术外的其他肿瘤专科治疗；
6、ECOG体能状态为0－2分；
7、主要器官功能正常，即符合下列标准：
（1）血常规检查标准需符合：（14天内未输血）
a. Hb≥90g/L:
b.ANC≥1.5x109/L;
c.PLT≥80x109／L；
（2）生化检查需符合以下标准
a．BIL＜1.25倍正常值上限（ULN）；
b．ALT和AST＜2.5xULN；如有肝转移，则ALT和AST<5XULN:
c．血清Cr≤ULN，内生肌酐清除率＞50ml／min（ Cockcroft-Gaut公式）；
8、在进行任何试验相关活动之前签署书面知情同意书；
9、研究者判断能够遵守研究方案；
10、 筛选时妊娠试验（针对具有生育能力的女性患者）阴性；
11、有生育能力的男性患者以及有生育能力和妊娠风险的女性患者必须同意在整个研究期间使用 2 种避孕方法（至少其中一种被视为高效的避孕方法）。
不具备生育能力的女性患者（即满足至少以下标准之一）：
—接受过子宫切除和/或双侧卵巢切除术，且有档案记录；
—已得到医学确认的卵巢功能衰退；
—处于绝经后状态，其定义为：在无其他病理学或生理学原因的前提下至少连续停经 12 个月，并且血清促卵泡激素（FSH）水平证实的状态与绝经后状态一致。
有签名并注明日期的知情同意书，表明患者（或合法代表，如果当地指南/实践规范允许）已被告知该研究的所有相关方面的信息。
12. 愿意并且能够遵从访视安排、治疗计划、实验室检验和其他研究程序的患者。

Inclusion criteria

1. aged 18 to 70 years old;
2. The histologic diagnosis of glioblastoma was grade IV by who;
3. After surgical treatment of glioblastoma;
4. MGMT promoter methylation was negative by PCR or NGS;
5. In the past, they did not receive any tumor specific treatment other than surgery for glioblastoma;
6. ECoG physical status was 0-2 points;
7. The function of the main organs is normal, that is to say, it meets the following standards:
(1) Blood routine examination standard should meet: (no blood transfusion within 14 days)
Hb>=90g/L; ANC.=1.5x10^9/L; PLT>=80x10^9/L;
(2) Biochemical examination should meet the following standardsL
Bil < 1.25 ULN;
ALT and AST < 2.5 ULN; if there is liver metastasis, ALT and AST < 5 ULN;
c. Serum Cr ≤ ULN, endogenous creatinine clearance rate > 50ml / min (Cockcroft gaut formula);

8. Sign written informed consent prior to any trial related activities;

9. The researcher judged that the protocol could be followed;

10. The pregnancy test (for women with fertility) was negative at the time of screening;

11. Fertile male patients, as well as women with fertility and pregnancy risk, must agree to use two contraceptive methods (at least one of which is considered to be highly effective) throughout the study period.

Female patients without fertility (i.e. meeting at least one of the following criteria)

- have undergone hysterectomy and / or bilateral oophorectomy and are documented;

- medically confirmed ovarian decline;

- postmenopausal status, defined as menopause for at least 12 months without other pathological or physiological reasons, and the status confirmed by serum follicle stimulating hormone (FSH) level is consistent with postmenopausal status.

A signed and dated informed consent form indicating that the patient (or legal representative, if permitted by local guidelines / practices) has been informed of all relevant aspects of the study.

12. Patients are willing to follow the treatment schedule and other treatment plans.

排除标准：

1. 既往接受过抗VEGF等靶点的抗血管生成药物治疗。
2. 5年内出现过或当前同时患有其它恶性肿瘤，治愈的子宫颈原位癌、非黑色素瘤的皮肤癌和表浅的膀胱肿瘤除外 [Ta（非浸润性肿瘤），Tis（原位癌）和T1（肿瘤浸润基膜）]；
3.随机分组前28天内存在明确的出血倾向或具有显著临床意义的出血症状，包括但不限于消化道出血、鼻腔出血（不包括鼻衄出血及回缩性涕血），以及持续的出血性疾病或凝血功能障碍性疾病；
4.随机分组前28天内出现过咳血或咯血者（定义为咳出或咯出≥1茶匙鲜血或小血块或只咳血无痰液），但不排除痰中带血者；
5.随机分组前28天内影像学显示肿瘤包绕重要血管，且研究者判定进入研究会引起出血风险；
6.已知对盐酸安罗替尼胶囊或本试验涉及的化疗药物过敏的受试者；
7.随机分组前28天内接受过全身免疫调节剂治疗（包括但不限于干扰素，白介素-2）；
8.受试者随机分组前出现以下任意一条严重的急性合并症：
①12个月内存在需住院治疗的不稳定性心绞痛和/或充血性心力衰竭或血管疾病（如，需手术修复的主动脉瘤或外周静脉血栓），或经研究者判断可能影响研究药物安全性评价的其他心脏损害（如，控制不良的心律失常,心肌梗塞或缺血）；
②6个月内存在食管胃底静脉曲张, 溃疡未愈，伤口未愈或骨折；
③6个月内存在腹瘘，胃肠穿孔，腹腔内脓肿或急性胃肠道出血病史；
④6个月内存在动脉血栓栓塞事件，NCI CTCAE 3级以上的静脉血栓栓塞，短暂性脑缺血发作（transient ischemic attack，TIA）， 脑血管意外（cerebral vascular accident，CVA），高血压危象或高血压脑病；
⑤28天内存在加重的慢性阻塞性肺病（Chronic Obstructive Pulmonary Disease ，COPD）或其他需要住院治疗的呼吸系统疾病；
⑥28天内具有需要静脉注射抗生素治疗的处于活动期的肺部感染和/或急性细菌或真菌感染；
⑦7天内存在肝功能异常引起的显性黄疸；
⑧2天内接受过较小的手术操作（包括置管，不包括经外周静脉穿刺中心静脉置管术）；
⑨目前患有高血压且经单一降压药物治疗无法获得良好控制（收缩压≥160 mmHg，舒张压≥100 mmHg）；或正在使用两种或以上降压药联合治疗；
9.筛选期的病毒学检测显示满足以下任何一项时：
①HBsAg阳性且外周血乙肝病毒脱氧核糖核酸(HBV DNA)滴度检测≥ 1 × 103 copies/L；
②Anti-HCV阳性；
③HIV阳性；
10.随机分组前28天内参加过其他抗肿瘤药物临床试验。

Exclusion criteria：

1. He has received anti angiogenic drugs with anti VEGF targets in the past.

2. Other malignancies have occurred or are currently suffering from other malignancies within 5 years, except for the cured cervical carcinoma in situ, non melanoma skin cancer and superficial bladder tumor [ta (non invasive tumor), tis (carcinoma in situ) and T1 (tumor infiltrating basement membrane)];

3. Within 28 days before randomization, there were definite bleeding tendency or bleeding symptoms with significant clinical significance, including but not limited to gastrointestinal bleeding, nasal bleeding (excluding epistaxis and retractive epistaxis), and persistent hemorrhagic diseases or coagulation disorders;

4. Patients who had hemoptysis or hemoptysis within 28 days before randomization (defined as coughing or coughing up more than 1 teaspoon of blood or small blood clot or only hemoptysis without sputum) within 28 days before randomization;

5. Within 28 days before randomization, the imaging showed that the tumor surrounded the important vessels, and the researchers determined that the risk of bleeding would be caused by entering the study;

6. Subjects known to be allergic to amlotinib hydrochloride capsules or chemotherapy drugs involved in this study;

7. Received systemic immunomodulators (including but not limited to interferon and interleukin-2) within 28 days before randomization;

8. Any one of the following severe acute complications occurred before randomization:

① Unstable angina pectoris and / or congestive heart failure or vascular disease (e.g., aortic aneurysm or peripheral venous thrombosis requiring surgical repair) requiring hospitalization within 12 months, or other cardiac damage (such as poorly controlled arrhythmias, myocardial infarction or ischemia) that may affect the safety evaluation of the study drug as judged by the investigator;

② There were esophageal and gastric varices, ulcer, wound or fracture within 6 months;

③ There was a history of abdominal fistula, gastrointestinal perforation, abdominal abscess or acute gastrointestinal hemorrhage within 6 months;

④ Within 6 months, there were arterial thromboembolism events, venous thromboembolism above NCI CTCAE grade 3, transient ischemic attack (TIA), cerebrovascular accident (CVA), hypertensive crisis or hypertensive encephalopathy;

⑤ Severe chronic obstructive pulmonary disease (COPD) or other respiratory diseases requiring hospitalization within 28 days;

⑥ Active pulmonary infection and / or acute bacterial or fungal infection requiring intravenous antibiotic treatment within 28 days;

⑦ There was dominant jaundice caused by abnormal liver function within 7 days;

⑧ Minor surgical procedures (including catheterization, excluding peripherally inserted central venous catheterization) were performed within 2 days;

⑨ At present, they are suffering from hypertension and can not be well controlled by single antihypertensive drugs (systolic blood pressure ≥ 160 mmHg, diastolic blood pressure ≥ 100 mmHg); or they are using two or more antihypertensive drugs in combination;

9. Virological tests during the screening period show that any of the following conditions are met:

① HBsAg positive and HBV DNA titer ≥ 1 × 103 copies / L in peripheral blood;

② Anti HCV was positive;

③ HIV positive;

10. Participated in clinical trials of other antitumor drugs within 28 days before randomization.

报错 笔记

研究实施时间：

Study execute time：

从 From 2020-08-01 00:00:00至 To 2024-07-01 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2020-07-01 00:00:00 至 To 2022-07-01 00:00:00

干预措施：

Interventions：

组别：

给药组

样本量：

 30

Group：

Case series

Sample size：

干预措施：

安罗替尼同步放疗：受试者入组后予以放射治疗，同步给予安罗替尼12mg进行口服，每天1次，1次12mg，口服2周休息1周，持续至放疗结束为止

干预措施代码：

Intervention：

Concurrent radiotherapy with arotinib: the subjects were treated with radiotherapy, and they were treated with oral administration of 12 mg of arotinib once a day, once a day for 2 weeks and rest for 1 week until the end of radiotherapy

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 湖北省 

市(区县)：

  

Country：

China

Province：

Hubei

City：

单位(医院)：

 华中科技大学同济医学院附属协和医院 

单位级别：

 三甲医院 

Institution
hospital：

Union Medical College Affiliated Hospital of Tongji Medical College, Huazhong University of science and technology

Level of the institution：

Tertiary A Hospital

测量指标：

Outcomes：

指标中文名：

总生存期

指标类型：

主要指标

Outcome：

Overall survival

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：

无

组织：

Sample Name：

No

Tissue：

人体标本去向

 其它  

说明

Fate of sample：

0thers  

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 岁 years
最大 Max age 70 岁 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）：

无

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

not yet

是否公开试验完成后的统计结果:

Calculated Results after the Study Completed public access:

公开/Public

盲法：

Blinding：

试验完成后的统计结果（上传文件）：

Calculated Results after
the Study Completed(upload file)：

是否共享原始数据：

IPD sharing

是Yes

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）：

暂时未定

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

Not yet decided

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：

CRF表格

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

CRF form

数据与安全监察委员会：

Data and Safety Monitoring Committee：

无/No

注册人：

Name of Registration：

  2020-11-21 04:48:06