中国临床试验注册中心 - 世界卫生组织国际临床试验注册平台一级注册机构

注册号： Registration number：	ChiCTR2200060726
最近更新日期： Date of Last Refreshed on：	2023-03-23 11:00:04
注册时间： Date of Registration：	2022-06-09 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	该研究未获得伦理委员会批准，请于批准后开始征募参试者，并与我们联系上传伦理批件。马来酸吡咯替尼片用于曲妥珠单抗标准辅助治疗后的HER2阳性早期或局部晚期乳腺癌的探索性、开放性、单臂临床研究
Public title：	An exploratory, open, single arm clinical study of pyrotinib maleate tablets in early HER2 positive or locally advanced breast cancer after standard adjuvant therapy with trastuzumab
注册题目简写：
English Acronym：
研究课题的正式科学名称：	马来酸吡咯替尼片用于曲妥珠单抗标准辅助治疗后的HER2阳性早期或局部晚期乳腺癌的探索性、开放性、单臂临床研究
Scientific title：	An exploratory, open, single arm clinical study of pyrotinib maleate tablets in early HER2 positive or locally advanced breast cancer after standard adjuvant therapy with trastuzumab
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：	刘洪斌	研究负责人：	袁晓荣
Applicant：	Hongbin Liu	Study leader：	Xiaorong Yuan
申请注册联系人电话： Applicant telephone：	+86 18648253549	研究负责人电话： Study leader's telephone：	+86 18647207790
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：	hongbinaabb@126.com	研究负责人电子邮件： Study leader's E-mail：	hongbinaabb@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：	内蒙古自治区包头市青山区团结大街18号	研究负责人通讯地址：	内蒙古自治区包头市青山区团结大街18号
Applicant address：	18 Tuanjie Street, Qingshan District, Baotou, Inner Mongolia Autonomous Region	Study leader's address：	18 Tuanjie Street, Qingshan District, Baotou, Inner Mongolia Autonomous Region
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：	包头市肿瘤医院
Applicant's institution：	Baotou Tumor Hospital
研究负责人所在单位：	包头市肿瘤医院
Affiliation of the Leader：	Baotou Tumor Hospital

是否获伦理委员会批准：	否
Approved by ethic committee：	No
伦理委员会批件文号： Approved No. of ethic committee：		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：
Name of the ethic committee：
伦理委员会批准日期： Date of approved by ethic committee：	2013-08-26 00:00:00
伦理委员会联系人：
Contact Name of the ethic committee：
伦理委员会联系地址：
Contact Address of the ethic committee：
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：

包头市肿瘤医院

Primary sponsor：

Baotou Tumor Hospital

研究实施负责（组长）单位地址：

内蒙古自治区包头市青山区团结大街18号

Primary sponsor's address：

18 Tuanjie Street, Qingshan District, Baotou, Inner Mongolia Autonomous Region

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：	中国	省(直辖市)：	江苏省	市(区县)：
Country：	China	Province：	Jiangsu	City：
单位(医院)：	江苏恒瑞医院股份有限公司	具体地址：	连云港经济技术开发区黄河路38号
Institution hospital：	Jiangsu Hengrui Hospital Co., Ltd	Address：	38 Huanghe Road, Lianyungang Economic and Technological Development Zone

经费或物资来源：

自筹

Source(s) of funding：

Self-funded

研究疾病：

乳腺癌

Target disease：

Breast cancer

研究疾病代码：

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：

主要研究目的：评价吡咯替尼治疗曲妥珠单抗辅助治疗后的HER2阳性乳腺癌患者的有效性次要研究目的：评价吡咯替尼治疗曲妥珠单抗辅助治疗后的HER2阳性乳腺癌患者的安全性

Objectives of Study：

Main objective: To evaluate the efficacy of Pyrotinib Maleate Tablets in the treatment of HER2 positive breast cancer patients after trastuzumab adjuvant therapy. Secondary objective: To evaluate the safety of Pyrotinib Maleate Tablets in patients with HER2 positive breast cancer after trastuzumab 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：

Inclusion criteria

1. Female patients aged 18-75 years;
2. ECOG score: 0-1;
3. The primary invasive lesions and lymph nodes of the breast must meet the following conditions at the same time:
(1) Histologically confirmed invasive breast cancer;
(2) Has received radical resection or breast conserving surgery for breast cancer: Patients who have received breast conserving surgery must be confirmed by pathological examination that there is no residual invasive cancer and ductal carcinoma in situ at the cutting edge; The incisional margin allows lobular carcinoma in situ to remain;
(3) For patients who did not receive neoadjuvant therapy, postoperative pathological examination showed lymph node metastasis (including lymph node micrometastasis); In patients receiving neoadjuvant therapy, postoperative pathology showed that there were invasive cancer residues in breast or axillary lymph nodes;
(4) The result of HER2 pathological test is positive, which is defined as the result of immunohistochemistry (IHC) is 3+ or the result of in situ hybridization (ISH) is HER2 gene amplification (HER2 / CEP17 >= 2.0 or average HER2 copy number / cell >= 6);
(5) There were no recurrent and metastatic diseases after operation;
4. If receiving neoadjuvant therapy in the past, at least 4 cycles of treatment must be completed, and the medication scheme must include chemotherapy and anti-HER2 treatment;
5. Trastuzumab or trastuzumab + patuzumab treatment for >= 24 weeks (8 dosing cycles) has been completed in the neoadjuvant and / or adjuvant treatment stage, and the time interval from the end of the last trastuzumab treatment course to entering this study must be <= 1 year;
6. Known hormone receptor status (ER and PGR);
7. The functional level of main organs must meet the following requirements (no blood transfusion, no use of leukocyte raising and platelet raising drugs within 2 weeks before screening):
(1) Blood routine
1) neutrophil (ANC) >= 1.5 x 10^9/L
2) platelet count (PLT) >= 90 x 10^9/L
3) hemoglobin (Hb) >= 90 g/L;
(2) Blood biochemistry
1) total bilirubin (TBIL) <= 1.5 x Upper limit of normal value (ULN);
2) alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <= 1.5 x ULN
3) alkaline phosphatase <= 2.5 x ULN
4) urea or urea nitrogen (BUN) and creatinine (CR) <= 1.5 x ULN
(3) Left ventricular ejection fraction (LVEF) >= 55%;
(4) 12 lead ECG: fridericia corrected QT interval (QTCF) < 470 msec.
8. Female patients without menopause or surgical sterilization: agree to abstinence or use effective non hormonal contraceptive methods during the study treatment and within 8 weeks after the last administration in the study treatment;
9. Voluntarily join this study, sign informed consent, have good compliance and are willing to cooperate with follow-up.

排除标准：

1.既往已发生乳腺局部或区域的复发性疾病；
2.肿瘤临床分期为IV期（转移性）乳腺癌；
3.双侧乳腺癌；
4.既往5年内除乳腺癌外的任何恶性肿瘤史，不包括已治愈的宫颈原位癌、皮肤基底细胞癌或鳞癌；
5.既往接受过包括吡咯替尼、拉帕替尼、奈拉替尼或其他酪氨酸激酶抑制剂，Ado-Trastuzumab Emtansine（T-DM1）的治疗，以及其它抗肿瘤生物治疗或肿瘤免疫疗法；
6.同时在其他临床试验中接受抗肿瘤疗法，包括内分泌疗法、双膦酸盐类疗法或免疫疗法；
7.在随机化前4周内接受过重大与乳腺癌无关的手术操作，或患者尚未从此类手术操作中完全恢复；
8.既往曾接受蒽环类药物者在新辅助/辅助治疗阶段的累计使用超过以下规定：阿霉素（Doxorubincin）累计用量超过400 mg/m2；表阿霉素（Epirubicin）累计用量超过800 mg/m2（如采用其他蒽环类药物，则以此量折算）；
9.严重心脏疾病或不适，包括但不限于下列疾病：
（1）心力衰竭或收缩功能障碍（LVEF < 50%）确诊史；
（2）高风险未控制的心律失常，如房性心动过速，静息心率 > 100 bpm，显著室性心律失常（如室性心动过速）或较高级别的房室传导阻滞（即 Mobitz Ⅱ二度房室传导阻滞或三度房室传导阻滞）；
（3）需要抗心绞痛药物治疗的心绞痛；
（4）具有临床意义的心脏瓣膜病；
（5）ECG显示有透壁性心肌梗塞；
（6）高血压患者的血压经药物控制不佳（收缩压 > 180 mmHg和/或舒张压 > 100 mmHg）；
10.无法吞咽、肠梗阻或存在影响药物服用和吸收的其他因素；
11.既往有确诊的神经或精神障碍病史，包括无自主行为能力或患有精神疾病的患者；
12.既往存在以腹泻为主要症状的胃肠疾病史；
13.已知对本方案药物组分有过敏史者；有免疫缺陷病史，包括HIV检测阳性，或患有其他获得性、先天性免疫缺陷疾病，或有器官移植史；
14.妊娠期、哺乳期女性患者，有生育能力且基线妊娠试验检测阳性的女性患者；
15.患有严重的伴随疾病或其他会干扰计划治疗的合并疾病，包括存在活动性感染的传染病，或研究者认为患者不适合参加本研究的其他任何情况。

Exclusion criteria：

1. Local or regional recurrent breast diseases have occurred in the past;
2. The clinical stage of the tumor is stage IV (metastatic) breast cancer;
3. Bilateral breast cancer;
4. History of any malignant tumor other than breast cancer in the past 5 years, excluding cured cervical carcinoma in situ, skin basal cell carcinoma or squamous cell carcinoma;
5. Previous treatment including pyrrolotinib, lapatinib, naratinib or other tyrosine kinase inhibitors, ADO trastuzumab emtansine (T-DM1), as well as other antitumor biotherapy or tumor immunotherapy;
6. Receive anti-tumor therapy in other clinical trials, including endocrine therapy, bisphosphonate therapy or immunotherapy;
7. The patient has received major surgery unrelated to breast cancer within 4 weeks before randomization, or the patient has not fully recovered from such surgery;
8. The cumulative use of anthracycline drugs in neoadjuvant / adjuvant treatment exceeds the following provisions: the cumulative dosage of doxorubicin exceeds 400 mg/m2; The cumulative dosage of epirubicin exceeds 800 mg/m2 (if other anthracyclines are used, this amount shall be converted);
9. Serious heart disease or discomfort, including but not limited to the following diseases:
(1) Confirmed history of heart failure or systolic dysfunction (LVEF < 50%);
(2) High risk uncontrolled arrhythmias, such as atrial tachycardia, resting heart rate > 100 bpm, significant ventricular arrhythmias (such as ventricular tachycardia) or higher-grade atrioventricular block (i.e. Mobitz II second degree atrioventricular block or third degree atrioventricular block);
(3) Angina pectoris requiring anti angina drugs;
(4) Heart valve disease with clinical significance;
(5) ECG showed transmural myocardial infarction;
(6) The blood pressure of patients with hypertension is poorly controlled by drugs (systolic blood pressure > 180 mmHg and / or diastolic blood pressure > 100 mmHg);
10. Inability to swallow, intestinal obstruction or other factors affecting drug administration and absorption;
11. Previous history of confirmed neurological or mental disorders, including patients without autonomous behavior ability or suffering from mental illness;
12. Previous history of gastrointestinal diseases with diarrhea as the main symptom;
13. Those who are known to have a history of allergy to the drug components of this scheme; Have a history of immune deficiency, including HIV test positive, or suffer from other acquired and congenital immune deficiency diseases, or have a history of organ transplantation;
14. Female patients during pregnancy and lactation, female patients with fertility and positive baseline pregnancy test;
15. Suffering from serious concomitant diseases or other combined diseases that will interfere with the planned treatment, including infectious diseases with active infection, or any other circumstances that the investigator believes the patient is not suitable for the study.

研究实施时间：

Study execute time：

从 From 2022-05-31 00:00:00至 To 2023-05-31 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2022-05-31 00:00:00 至 To 2023-04-30 00:00:00

干预措施：

Interventions：

组别：	试验组	样本量：	40
Group：	Test group	Sample size：	40
干预措施：	马来酸吡咯替尼片	干预措施代码：
Intervention：	Pyrotinib Maleate Tablets	Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：	中国	省(直辖市)：	内蒙古自治区	市(区县)：
Country：	China	Province：	Inner Mongolia Autonomous Region	City：
单位(医院)：	包头市肿瘤医院	单位级别：	三级甲等
Institution hospital：	Baotou Tumor Hospital	Level of the institution：	Tertiary A

测量指标：

Outcomes：

指标中文名：	无浸润性肿瘤复发生存率	指标类型：	主要指标
Outcome：	invasive disease-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：	无病生存期	指标类型：	次要指标
Outcome：	disease-free survival	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	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：	Security	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：

标本中文名：	尿液	组织：
Sample Name：	urine	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	75	岁 years

性别：

女性

Gender：

Female

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)：

None

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）：	点击下载
Calculated Results after the Study Completed(upload file)：	download

是否共享原始数据： IPD sharing	否No
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）：	论文发表
The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：	Paper publication
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：	病例记录表
Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：	CRF
数据与安全监察委员会： Data and Safety Monitoring Committee：	有/Yes
注册人： Name of Registration：	2022-06-09 12:46:17