今天是:2019-07-21 星期日

新辅助同步放化疗联合甲磺酸阿帕替尼治疗局部进展期HER2阴性Siewert Ⅱ型、Ⅲ型 食管胃结合部腺癌的前瞻性、随机、对照、 多中心III期临床研究
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注册号:

Registration number:

ChiCTR1900024092 

最近更新日期:

Date of Last Refreshed on:

2019-07-01 

注册时间:

Date of Registration:

2019-06-25 

注册号状态:

预注册  

Registration Status:

Prospective registration  

注册题目:

新辅助同步放化疗联合甲磺酸阿帕替尼治疗局部进展期HER2阴性Siewert Ⅱ型、Ⅲ型 食管胃结合部腺癌的前瞻性、随机、对照、 多中心III期临床研究 

Public title:

A prospective, randomized, controlled, multicenter, phase III study of apatinib plus concurrent neoadjuvant chemoradiotherapy for Siewert II ,III of locally advanced HER-2 negative adenocarcinoma at gastroesophageal junction 

注册题目简写:

 

English Acronym:

 

研究课题的正式科学名称:

新辅助同步放化疗联合甲磺酸阿帕替尼治疗局部进展期HER2阴性Siewert Ⅱ型、Ⅲ型 食管胃结合部腺癌的前瞻性、随机、对照、 多中心III期临床研究 

Scientific title:

A prospective, randomized, controlled, multicenter, phase III study of apatinib plus concurrent neoadjuvant chemoradiotherapy for Siewert II ,III of locally advanced HER-2 negative adenocarcinoma at gastroesophageal junction 

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:

赵群 

研究负责人:

赵群 

Applicant:

Qun Zhao 

Study leader:

Qun Zhao 

申请注册联系人电话:

Applicant telephone:

+86 13930162111 

研究负责人电话:

Study leader's telephone:

+86 13930162111 

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:

Zhaoqun516@126.com 

研究负责人电子邮件:

Study leader's E-mail:

Zhaoqun516@126.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:

河北省石家庄市健康路12号 

研究负责人通讯地址:

河北省石家庄市健康路12号医大四院外三科  

Applicant address:

12 Jiankang Road, Shijiazhuang, Hebei, China  

Study leader's address:

12 Jiankang Road, Shijiazhuang, Hebei, 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:

河北医科大学第四医院 

Applicant's institution:

Fourth Hospital of Hebei 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:

2019048 

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:

河北医科大学第四医院药物临床试验伦理委员会 

Name of the ethic committee:

The Ethics Commitee for Drug Clinical Trial, the Fourth Hospital of Hebei Medical University 

伦理委员会批准日期:

Date of approved by ethic committee:

2019-05-27 

伦理委员会联系人:

张俊敏 

Contact Name of the ethic committee:

Junmin Zhang 

伦理委员会联系地址:

河北省石家庄市健康路12号 

Contact Address of the ethic committee:

12 Jiankang Road, Shijiazhuang, Hebei, 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:

河北医科大学第四医院 

Primary sponsor:

Fourth Hospital of Hebei Medical University 

研究实施负责(组长)单位地址:

河北省石家庄市健康路12号 

Primary sponsor's address:

12 Jiankang Road, Shijiazhuang, Hebei, 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):

河北

市(区县):

石家庄

Country:

China

Province:

Hebei

City:

Shijiazhuang

单位(医院):

河北医科大学第四医院

具体地址:

健康路12号

Institution
hospital:

the Fourth Hospital of Hebei Medical University

Address:

12 Jiankang Road

经费或物资来源:

自费 

Source(s) of funding:

self-pay 

研究疾病:

食管胃结合部腺癌 

Target disease:

gastroesophageal junction adenocarcinoma 

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:

研究目的:

评价新辅助同步放化疗联合甲磺酸阿帕替尼治疗SiewertⅡ型、Ⅲ型局部进展期HER2阴性食管胃结合部腺癌的安全性和有效性。 

Objectives of Study:

The purpose of this study is to assess the efficacy and safety of patients who receive concurrent neoadjuvant chemoradiotherapy for Siewert II, III of locally advanced HER-2 negative adenocarcinoma at gastroesophageal junction. 

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 

Study design:

Parallel 

纳入标准:

1. 受试者签署知情同意书时年龄为18-70岁,男女不限;。 2. 经组织学或细胞学确诊为腺癌,经IHC或FISH检测HER-2为阴性; 3. 胃镜确诊为SiewertⅡ型或者Ⅲ型的食管胃结合部腺癌,肿瘤长径≤8cm; 4. 根据CT/MRI检查确诊分期为Ⅲ期的患者(依据第八版AJCC分期); 5. 具有可测量病灶(螺旋CT扫描≥10mm,满足RECIST 1.1标准); 6. ECOG PS:0-1分; 7. 预期的生存期≥6个月。 8. 按照方案要求进行所有的筛选期实验室检查,而且需要在首次用药前的14天内进行。筛查所做的实验室检查的值必须符合下列标准: 1)血常规检查:(前14天内未输血、未使用G-CSF、未使用药物纠正) a) 血红蛋白(HB)≥90 g/L; b) 中性粒细胞计数绝对值(ANC)≥1.5×10^9/L; c) 血小板计数(PLT)≥100×10^9/L; d) 白细胞计数(WBC)≥4.0×10^9/L并且≤15×10^9/L; 2)生化检查:(前14天内未输血或白蛋白) e) AST和ALT≤1.5?ULN(如存在肿瘤肝转移,≤5xULN); f) ALP≤2.5xULN; g) TBiL≤1.5xULN; h) Cr≤1.5xULN,同时肌酐清除率(CrCL)≥60 mL/min(Cockcroft-Gault公式); i) APTT≤1.5xULN,同时INR或PT≤1.5xULN(未接受抗凝治疗)。 9. 育龄妇女必须在入组前7天内进行妊娠试验(血清或尿液),且结果为阴性,并且愿意在试验期间和末次给予试验药物后8周采用适当的方法避孕。对于男性,应为手术绝育,或同意在试验期间和末次给予试验药物后8周采用适当的方法避孕; 10. 受试者自愿加入本研究,签署知情同意书,依从性好,配合随访。 

Inclusion criteria

1. Adult patients (18 to 70 years old) at the time of voluntarily signing informed consent; 2. Histologically or cytologically confirmed adenocarcinoma. The her-2 negative was detected by immunohistochemistry or fluorescence in situ hybridization; 3. Confirmed to Siewert II, III of locally advanced adenocarcinoma at gastroesophageal junction and tumor long diameter <= 8 cm by gastroscopy; 4. Patients with Stage for III by CT/MRI (According to the eighth edition of AJCC); 5. Patients with measurable lesions(measuring>=10mm on spiral CT scan, satisfying the criteria in RECIST1.1); 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1; 7. Life expectancy greater than or equal to 6 months; 8. Subject must meet all of the following criteria based on the laboratory tests within 14 days prior to the first dose of study treatment. (1) Baseline blood indicators meet the following criteria: HB>=80g/L; ANC>=1.5x10^9/L; PLT>=90x10^9/L; WBC>=4.0x10^9/L and <=15x10^9/L (2) Baseline biochemical indicators meet the following criteria: ALT and AST<=2.5xULN, but<=5xULN, if the transferanse elevation is due to liver metastases; ALP<=2.5xULN; TBiL<=1.5xULN; Cr<=1.5xULNEndogenous creatinine clearance rate >= 60 ml/min (Cockcroft-Gault formula); APTT<=1.5xULNand INR or PT<=1.5xULN; 9. Women of childbearing age must have contraceptive measures or have test pregnancy (serum or urine) enroll the study before 7 days, and the results must be negative, and take the methods of contraception during the test and the last to have drugs after 8 weeks. Men must be contraception or has sterilization surgery during the test and the last to have drugs after 8 weeks; 10. Participants were willing to join in this study, and written informed consent, good adherence, cooperate with the follow-up. 

排除标准:

1. 已证实对阿帕替尼、卡培他滨及奥沙利铂过敏者; 2. 腹腔冲洗液细胞学检查表明肿瘤脱落细胞为阳性者; 3. 患有高血压且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),无法控制的冠心病及心律失常,III-IV级心功能不全者; 4. 具有影响口服药物的多种因素(比如无法吞咽、恶心、呕吐、慢性腹泻和肠梗阻等); 5. 具有明确的胃肠道出血倾向的患者,包括下列情况:有局部活动性溃疡病灶,且大便潜血阳性不可入组;2个月内有黑便、呕血病史者; 6. 凝血功能异常(INR>1.5、APTT>1.5 ULN),具有出血倾向者; 7. 怀孕或哺乳期妇女; 8. 5年内患有其他恶性肿瘤的患者(除外可治愈的皮肤基底细胞癌和宫颈原位癌); 9. 具有精神类药物滥用史且无法戒除者或有精神障碍的患者; 10. 4周内参加过临床试验者; 11. 研究者认为不适合纳入者。 

Exclusion criteria:

1. Allergic to apatinib, capecitabine and oxaliplatin; 2. The cytological examination of the abdominal cavity washing fluid showed that the tumor shedding cells were positive; 3. Have high blood pressure and antihypertensive drug treatment can not control (systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg), Uncontrolled coronary heart disease and arrhythmia ,class III-IV cardiac insufficiency; 4. A variety of factors influencing oral drugs (such as unable to swallow, nausea, vomiting, chronic diarrhea and intestinal obstruction, etc); 5. Patients with tendency of gastrointestinal bleeding, including the following: a local active ulcerative lesions, and defecate occult blood; Has melena and hematemesis in two months; 6. Coagulant function abnormality (INR > 1.5 ULN, APTT > 1.5 ULN), with bleeding tendency; 7. Pregnant or lactating women; 8. Patients with other malignant tumors within 5 years (except for curable skin basal cell carcinoma and cervical carcinoma in situ); 9. History of psychiatric drugs abuse and can't quit or patients with mental disorders; 10. Less than 4 weeks from the last clinical trial; 11. The researchers think inappropriate. 

研究实施时间:

Study execute time:

From2019-06-25To 2024-04-30 

干预措施:

Interventions:

组别:

试验组

样本量:

90

Group:

experimental group

Sample size:

干预措施:

术前:甲磺酸阿帕替尼:剂量为250 mg/日,餐后服用,每日一次(每日尽量同一时间服用),28天一周期,2周期 XELOX:卡培他滨1000mg/m2 bid d1-14,奥沙利铂130 mg/m2 Ivgtt d1,q3w,2周期 放疗:共45Gy/25f (1.8Gy/f/d,5次/周) 术后:卡培他滨1000mg/m2 bid d1-14,6周期

干预措施代码:

Intervention:

Preoperative: Apatinib 250mg q.d. p.o. q4w; XELOX: Capecitabine 1000mg/m2 b.i.d. d1-14, Oxaliplatin 130 mg/m2 i.v.gtt. d1 q3w; Radiotherapy 45Gy/25f (1.8Gy/f/d, 5 f/w) Postoperative: Capecitabine 1000mg/m2 b.i.d. d1-14 q3w 2 cycles.

Intervention code:

组别:

对照组

样本量:

90

Group:

Active Comparator

Sample size:

干预措施:

术前:XELOX:卡培他滨1000mg/m2 bid d1-14,奥沙利铂130 mg/m2 Ivgtt d1,q3w,2周期 放疗:共45Gy/25f (1.8Gy/f/d,5次/周) 术后:卡培他滨1000mg/m2 bid d1-14,6周期

干预措施代码:

Intervention:

Preoperative: XELOX: Capecitabine 1000mg/m2 b.i.d. d1-14, Oxaliplatin 130 mg/m2 i.v.gtt. d1 q3w, Radiotherapy: 45Gy/25f (1.8Gy/f/d,5 f/w) ; Postoperative: Capecitabine 1000mg/m2 b.i.d. d1-14 q3w 6 cycles.

Intervention code:

研究实施地点:

Countries of recruitment and research settings:

国家:

中国 

省(直辖市):

河北省 

市(区县):

石家庄 

Country:

China 

Province:

Hebei 

City:

Shijiazhuang 

单位(医院):

河北医科大学第四医院 

单位级别:

三级 

Institution
hospital:

Fourth Hospital of Hebei Medical University  

Level of the institution:

Tertiary A 

测量指标:

Outcomes:

指标中文名:

病理缓解率

指标类型:

主要指标 

Outcome:

The pathological complete response rate (pCR)

Type:

Primary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

无进展生存期

指标类型:

主要指标 

Outcome:

Disease-free survival (DFS)

Type:

Primary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

客观缓解率

指标类型:

次要指标 

Outcome:

Objective response rate (ORR)

Type:

Secondary 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:

次要指标 

Outcome:

Disease Control Rate (DCR)

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

R0切除率

指标类型:

次要指标 

Outcome:

R0-resection rate

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

总生存期

指标类型:

次要指标 

Outcome:

Overall survival (OS)

Type:

Secondary 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

指标类型:

次要指标 

Outcome:

Safety

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:

正在进行

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):

随机数字表由统计单位的专业人员提供。

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

The table of random digit will be offered by the professional staff in statistical unit.

盲法:

open

Blinding:

open

试验完成后的统计结果(上传文件):

Calculated Results after
the Study Completed(upload file):

原始数据公开时间:

The time of sharing IPD:

即时公开/Real time access

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):

发表文章

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

publish articles

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:

病例报告表

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

CRF

数据管理委员会:

Data Managemen Committee:

有/Yes

注册人:

Name of Registration:

 2019-06-25
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