ChiCTR1900026291 版本V1.0 版本创建时间2019/11/20 10:40:21 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：

ChiCTR1900026291 

最近更新日期：

Date of Last Refreshed on：

2019-09-29 14:21:48 

注册时间：

Date of Registration：

2019-09-29 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

盐酸安罗替尼联合SOX方案（替吉奥+奥沙利铂）治疗Ⅳ期胃癌单臂、单中心临床研究方案

Public title：

Anlotinib Combined with SOX Regimen (S1 [Tegafur, Gimeracil and Oteracil Porassium Capsules] + oxaliplatin) in Treating Stage IV Gastric Cancer: A Single-Armed and Single Center Clinical Trial

注册题目简写：

English Acronym：

研究课题的正式科学名称：

盐酸安罗替尼联合SOX方案（替吉奥+奥沙利铂）治疗Ⅳ期胃癌单臂、单中心临床研究方案

Scientific title：

Anlotinib Combined with SOX Regimen (S1 [Tegafur, Gimeracil and Oteracil Porassium Capsules] + oxaliplatin) in Treating Stage IV Gastric Cancer: A Single-Armed and Single Center Clinical Trial

研究课题代号(代码)：

Study subject ID：

 国家自然科学基金（81502401 和 31670828）

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：

王娟 

研究负责人：

季刚 

Applicant：

Juan Wang 

Study leader：

Gang Ji 

申请注册联系人电话：

Applicant telephone：

+86 29 84771533

研究负责人电话：

Study leader's telephone：

+86 29 84771525

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：

wangjuan861016@126.com

研究负责人电子邮件：

Study leader's E-mail：

jigangfmmu@163.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：

陕西省西安市新城区长乐西路127号

研究负责人通讯地址：

陕西省西安市新城区长乐西路127号

Applicant address：

127 West Changle Road, Xi'an, Shaanxi, China

Study leader's address：

127 West Changle Road, Xi'an, Shaanxi, China

申请注册联系人邮政编码：

Applicant postcode：

710032

研究负责人邮政编码：

Study leader's postcode：

710032

申请人所在单位：

第四军医大学附属西京医院

Applicant's institution：

Xijing Hospital, The Fourth Military Medical University

研究负责人所在单位：

第四军医大学附属西京医院

Affiliation of the Leader：

Xijing Hospital, The Fourth Military Medical University

是否获伦理委员会批准：

是/Yes

Approved by ethic committee：

Yes

伦理委员会批件文号：

Approved No. of ethic committee：

KY20192111-F-1

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：

第四军医大学第一附属医院（西京医院）伦理委员会

Name of the ethic committee：

Ethics Committee at the First Affliated Hospital (Xijing Hospital) of Fourth Military Medical University

伦理委员会批准日期：

Date of approved by ethic committee：

1990-01-01 00:00:00

伦理委员会联系人：

伍晓晓

Contact Name of the ethic committee：

Ethics Committee at the First Affliated Hospital (Xijing Hospital) of Fourth Military Medical University

伦理委员会联系地址：

陕西省西安市新城区长乐西路127号

Contact Address of the ethic committee：

127 West Changle Road, Xi'an, Shaanxi, 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：

第四军医大学附属西京医院

Primary sponsor：

Gang Ji

研究实施负责（组长）单位地址：

陕西省西安市新城区长乐西路127号

Primary sponsor's address：

127 West Changle Road, Xi'an, Shaanxi, 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)：

陕西省

市(区县)：

西安市

Country：

China

Province：

Shaanxi

City：

Xi'an

单位(医院)：

第四军医大学附属西京医院

具体地址：

陕西省西安市新城区长乐西路127号

Institution
hospital：

Xijing Hospital, The Fourth Military Medical University

Address：

127 West Changle Road, Xi'an, Shaanxi, China

经费或物资来源：

国家自然科学基金（81502401 和 31670828）

Source(s) of funding：

National Natural Science Foundation of China (81502401 and 31670828)

Target disease：

Gastric Cancer

Target disease code：

研究类型：

观察性研究

Study type：

Observational study

研究所处阶段：

 上市后药物 

Study phase：

4

研究设计：

单臂 

Study design：

Single arm 

研究目的：

评价盐酸安罗替尼联合SOX方案（替吉奥+奥沙利铂）用于Ⅳ期胃癌患者的有效性和安全性  

Objectives of Study：

To evaluate the safety and efficacy of anlotinib combined with the S-1 (tegafur, gimeracil, and oteracil potassium capsules) and oxaliplatin(SOX) regimen in patients with stage IV gastric cancer.

药物成份或治疗方案详述：

盐酸安罗替尼胶囊口服（早餐前）每日1次，每次12mg，连续用药2周停1周，替吉奥40mg早60mg晚，连续用药2周停1周，奥沙利铂130mg/m 2 ivdrip d1。每3周为一周期。 疾病控制（CR+ PR+SD）且不良反应可以耐受的患者，持续用药1年。未出现疾病进展（PD）前，不能进行其它抗肿瘤治疗。每6周（2个周期）评估一次疗效。研究者认为患者不适合继续用药或疗效评价为PD时用药结束。 

Description for medicine or protocol of treatment in detail：

Anlotinib hydrochloride capsules were taken orally (before breakfast) once a day, 12mg each time, 2 weeks on and 1 week off; S1 40mg in the morning and 60mg at night, 2 weeks on and 1 week off; oxaliplatin 130 mg/m 2 IV drip d1, 3 weeks a cycle. Patients with disease control (complete response [CR] + partial response [PR] + stable disease [SD]) who could tolerate adverse reactions continued to take medication for 1 year, and did not take any other type of anti-tumor therapy until disease progression had occurred. Patients were evaluated every 6 weeks (2 cycles). Treatment were stopped when the investigators concluded that the patients were no longer good candidates to continue the presenting regimen or when the efficacy evaluation deemed disease to be progressing. 

纳入标准：

1）患者提供书面知情同意书参与研究。
2）患者通过活检/病理诊断为IV期胃腺癌（任何T，N，M1，胃外可测量的病变[RECIST 1.1标准]，包括无法切除的局部晚期肿瘤，R1或R2切除的晚期肿瘤，以及复发或R0切除术后的转移状态；
3）患者年龄在18岁以上，东部肿瘤协作组的表现状态评分为0~2分。
4）主要脏器功能在治疗前7天内符合以下标准：常规检查标准（14天内未输血）：血红蛋白≥90g/ L，绝对中性粒细胞计数≥1.5×109 / L，血小板（PLT）≥ 80×109 / L;化学小组测试符合以下标准：总胆红素（TBIL）≤正常上限（ULN）的1.5倍，丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）≤2.5xULN或如果并发肝转移则ALT和AST≤5xULN，血清肌酐≤1.5xULN或肌酐清除率≥60mL/ min。
5）育龄妇女同意在研究期间和研究后的前6个月内使用避孕药具（例如宫内避孕器具，避孕药具或避孕套）;在研究登记前7天进行了血清或尿液妊娠试验阴性，并且是非哺乳期患者。男性候选人同意在研究期间和研究后的前6个月内使用避孕措施。

Inclusion criteria

1. The patients provided written informed consent form to participate in the study;
2. Patients were diagnosed with stage IV gastric adenocarcinoma by biopsy/pathology (any T, N, M1, with extra-gastric measurable lesions [RECIST 1.1 criteria] including unresectable locally advanced tumors, advanced tumors by R1 or R2 resection, and recurrence or metastasis status post R0 resection;
3. Patients aged 18 years or older with an Eastern Cooperative Oncology Group performance status score of 0 to 2 points;
4. Functions of the major organs met the following criteria within 7 days before treatment: routine examination standard (without blood transfusion within 14 days): hemoglobin >=90g/L, absolute neutrophil count >=1.5x10^9/L, platelet (PLT) >=80x10^9/L; and chemistry panel test met the following criteria: total bilirubin (TBIL) <=1.5 ULN, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <=2.5 ULN or if complicated with liver metastasis then ALT and AST <=5 ULN, serum creatinine <=1.5 ULN or creatinine clearance >=60mL/min;
5. Women of childbearing age agreed to use contraceptives (e.g., intrauterine devices, contraceptives, or condoms) during the study period and within the first 6 months after the study; had a negative serum or urine pregnancy test 7 days prior to study enrollment, and were non-lactating patients. Male candidates agreed to use contraception during the study period and within the first 6 months after the study.

排除标准：

1）先前用安非他替治疗的患者。
2）之前接受过VEGFR-酪氨酸激酶抑制剂治疗的患者，如舒尼替尼，索拉非尼，法尼替尼，阿帕替尼和瑞格非尼。
3）目前患有或之前患有其他恶性肿瘤的患者，除原位宫颈癌，非黑色素瘤皮肤癌和浅表性膀胱肿瘤（Ta [非侵袭性肿瘤]，Tis [原位癌]和T1） （肿瘤浸润性基底膜））
4）患者在入组前4周或研究期间接受全身抗肿瘤治疗，包括细胞毒性治疗，信号转导抑制剂和免疫治疗，或者在研究前6周接受丝裂霉素C治疗。患者在入组前4周接受延长放疗，或在入组前2周接受野外放射治疗。
5）由于先前治疗而导致的不良反应1级常用术语标准（CTCAE）（4.0）尚未解决的毒性作用，但不包括低于2级的脱发和奥沙利铂诱导的神经毒性。
6）有任何出血迹象或病史的患者，无论严重程度如何，出血或出血事件≥注册前4周内CTCAE 3级;或未愈合的伤口，溃疡或骨折。有明显胃肠道出血可能性的患者，包括以下情况：局部活动性溃疡病变，以及大便隐血2+;有近2个月有黑色素瘤，呕血，粪便隐血1+病史的患者，以及未经手术切除的胃肿瘤原发病灶患者，主要研究人员认为有胃肠道出血的高风险。
7）影响口服药物服用能力的医疗条件（例如，无法吞咽，慢性腹泻）。
8）胸腔积液或腹水引起呼吸道症状的患者（≥CTCAE2级呼吸困难（2级呼吸困难是指低强度体力活动时呼吸短促，影响日常生活的器械活动）.
9）患有以下任何一种情况的患者严重和/或不受控制的疾病：服用一种抗高血压药物但血压仍不令人满意（收缩压≥150mmHg，舒张压≥100mmHg）;根据纽约心脏协会分类，患有1级或以上的心肌缺血或心肌梗塞，恶性心律失常（包括QTC≥480ms）和≥2级充血性心力衰竭;有效或无法控制的严重感染（≥CTCAE2级感染）;肝硬化，失代偿性肝病或活动性肝炎;需要血液透析或腹膜透析的肾功能衰竭;免疫缺陷病史，包括HIV阳性或其他获得性先天性免疫缺陷病，或器官移植史;糖尿病控制不佳（空腹血糖[FBG]> 10mmol / L）;尿液分析表明尿蛋白≥++并确认> 1.0 g 24 h尿蛋白;癫痫发作需要治疗;精神病药物滥用史无法戒烟;精神障碍;脑转移伴神经症状或症状控制不到2个月。
10）在入组前28天内接受过大手术治疗，开放活检或显着创伤的患者。
11）动脉/静脉血栓形成引起6个月内发生的事件，如脑血管意外（包括短暂性脑缺血发作），深静脉血栓形成和肺栓塞。
12）参与其他抗肿瘤药物临床试验或在4周内接受其他临床试验的患者。

Exclusion criteria：

1. Patients who were previously treated with anlotinib;
2. Patients who were previously treated with VEGFR-tyrosine kinase inhibitors such as sunitinib, sorafenib, famitinib, apatinib, and regorafenib;
3. Patients currently suffering from or who previously had other malignant tumors within 5 years, except cervical cancer in situ, non-melanoma skin cancer, and superficial bladder tumors (Ta [non-invasive tumor], Tis [in situ carcinoma] and T1 (tumor-infiltrating basement membrane]);
4. Patients received systemic anti-tumor therapy including cytotoxic therapy, signal transduction inhibitors, and immunotherapy 4 weeks prior to enrollment or during the study or who were treated with mitomycin C in the 6 weeks before study. Patients received extended-filed radiation therapy in the 4 weeks before enrollment or involved field radiation therapy in the 2 weeks prior to enrollment;
5. Patients with unresolved toxic effects above Grade 1 Common Terminology Criteria for Adverse Events(CTCAE) (4.0) due to prior treatment, but not including alopecia and oxaliplatin-induced neurotoxicity that was lower than Grade two;
6. Patients with any sign or history of hemorrhage, regardless of severity, with any bleeding or bleeding episodes >= CTCAE Grade 3 within 4 weeks prior to enrollment; or with unhealed wounds, ulcers, or fractures. Patients with a clear possibility of gastrointestinal bleeding, including the following conditions: local active ulcer lesions, and fecal occult blood 2+; patients with a history of melanoma, hematemesis, fecal occult blood 1+ in the past 2 months, and patients with gastric tumor primary lesions without surgically resection, and considered to be at high risk of having gastrointestinal bleeding by main research staff;
7. Medical conditions that affected ability to take oral medication (e.g., inability to swallow, chronic diarrhea);
8. Patients with pleural effusion or ascites, causing respiratory symptoms (>=CTCAE Grade 2 dyspnea (level 2 dyspnea refers to shortness of breath during low-intensity physical activity, affecting instrumental activities of daily living);
9. Patients with any of the following severe and/or uncontrolled diseases: taking one antihypertensive medication but still having unsatisfactory blood pressure (systolic blood pressure >=150 mmHg, diastolic blood pressure >=100 mmHg); suffering from Grade 1 or above myocardial ischemia or myocardial infarction, malignant arrhythmia (including QTC >= 480ms) and >=Grade 2 congestive heart failure according to New York Heart Association classification; active or uncontrolled severe infection (>=CTCAE Grade 2 infection); cirrhosis, decompensated liver disease, or active hepatitis; renal failure requiring hemodialysis or peritoneal dialysis; history of immunodeficiency including HIV-positive or other acquired, congenital immunodeficiency diseases, or a history of organ transplantation; poorly controlled diabetes (fasting blood glucose [FBG] >10mmol/L); urinalysis indicating urine protein >=++ and confirmed >1.0 gof 24-h urine protein; seizures that require treatment; history of psychotic medication abuse and are unable to quit; mental disorder; brain metastases with neurological symptoms or symptoms controlled for less than 2 months;
10. Patients who had major surgical treatment, open biopsy, or significant traumatic injury within 28 days before enrollment;
11. Arterial/venous thrombosis caused events that occurred within 6 months such as cerebrovascular accidents (including transient ischemic attacks), deep vein thrombosis, and pulmonary embolism;
12. Patients who participated in other clinical trials of anti-tumor medications or are undergoing other clinical trials within 4 weeks.

研究实施时间：

Study execute time：

从 From 2019-10-01 00:00:00至 To 2024-09-30 00:00:00  

征募观察对象时间：

Recruiting time：

从From 2019-10-01 00:00:00 至 To 2024-09-30 00:00:00  

干预措施：

Interventions：

组别：

Case series

样本量：

150

Group：

Case series

Sample size：

干预措施：

安罗替尼联合化疗

干预措施代码：

Intervention：

Anlotinib Combined with SOX Regimen

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 陕西省 

市(区县)：

 西安市 

Country：

China 

Province：

Shaanxi 

City：

Xi'an 

单位(医院)：

西京医院 

单位级别：

三级甲等教学医院 

Institution
hospital：

Xi Jing Hospital

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

客观缓解率

指标类型：

主要指标

Outcome：

objective response rate

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

疾病无进展生存期

指标类型：

主要指标

Outcome：

progression-free survival

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

疾病控制率

指标类型：

主要指标

Outcome：

disease control rate

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

总体生存

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：

指标中文名：

安全性指标

指标类型：

次要指标

Outcome：

safety indicator

Type：

Secondary 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 岁 years
最大 Max age 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）：

单臂研究，无随机方法

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

N/A

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：

N/A

Blinding：

N/A

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

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）：

我们将在发布论文时公开发布原始数据，并为原始数据构建共享路径。

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

We will publish the original data publicly when publishing the paper and build a sharing path for the original data.

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：

数据管理： 研究者对每位患者在试验中的相关资料均应及时、真实地记录在研究病历中；研究者或其授权人员将相关资料填写在病例报告表中。保证录入的内容与研究病历一致。为保证患者的隐私权，患者姓名使用代码。完成研究后病例报告表由申办单位和研究单位保存。 数据锁定： 数据审核无误，由主要研究者、数据管理员、统计人员和监查员对数据进行锁定。锁定后的数据文件原则上不再做改动。任何数据改变都需要得到主要研究者、统计学家和数据管理员共同签署同意书后方可进行。

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

Investigators recorded the relevant data of each patient in the research medical record in a timely and true manner. The researcher or his authorized personnel filled in the relevant information in the case report form, and ensured that the content entered was consistent with the research medical record. To ensure patient privacy, codes were used instead of the patient’s name. After completion of the study, the case report form was kept by the sponsor and the research facility and it was ensured that data were correctly entered. Key investigators, data administrators, statisticians, and auditors determined the dataset for analysis. Under most circumstances, the determined data file were no longer changed.

数据与安全监察委员会：

Data and Safety Monitoring Committee：

暂未确定/Not yet

注册人：

Name of Registration：

  2019-09-29 14:21:48