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：	ChiCTR2500108436
最近更新日期： Date of Last Refreshed on：	2025-08-29 17:16:36
注册时间： Date of Registration：	2025-08-29 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	SHR-A1811单药或联合帕妥珠单抗治疗吡咯替尼经治进展的HER2阳性晚期乳腺癌脑转移患者的前瞻性临床研究
Public title：	A prospective clinical study of SHR-A1811 monotherapy or combined with pertuzumab in the treatment of HER2-positive advanced breast cancer with brain metastases after progression with pyrotinib
注册题目简写：
English Acronym：
研究课题的正式科学名称：	SHR-A1811单药或联合帕妥珠单抗治疗吡咯替尼经治进展的HER2阳性晚期乳腺癌脑转移患者的前瞻性临床研究
Scientific title：	A prospective clinical study of SHR-A1811 monotherapy or combined with pertuzumab in the treatment of HER2-positive advanced breast cancer with brain metastases after progression with pyrotinib
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：	吴涛	研究负责人：	吴涛
Applicant：	Wutao	Study leader：	Wutao
申请注册联系人电话： Applicant telephone：	+86 158 7364 4000	研究负责人电话： Study leader's telephone：	+86 158 7364 4000
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：	20689452@qq.com	研究负责人电子邮件： Study leader's E-mail：	20689452@qq.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：	湖南省常德市武陵区人民路818路 415000	研究负责人通讯地址：	湖南省常德市武陵区人民路818路 415000
Applicant address：	818 Renmin Road, Wuling District, Changde City, Hunan Province	Study leader's address：	818 Renmin Road, Wuling District, Changde City, Hunan Province
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：	常德市第一人民医院
Applicant's institution：	Changde First People's Hospital
研究负责人所在单位：	常德市第一人民医院
Affiliation of the Leader：	Changde First People's 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：
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：

常德市第一人民医院

Primary sponsor：

Changde First People's Hospital

研究实施负责（组长）单位地址：

湖南省常德市武陵区人民路818路

Primary sponsor's address：

818 Renmin Road, Wuling District, Changde City, Hunan Province

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：	中国	省(直辖市)：	湖南	市(区县)：
Country：	China	Province：	Hunan	City：
单位(医院)：	常德市第一人民医院	具体地址：	湖南省常德市武陵区人民路818路
Institution hospital：	Changde First People's Hospital	Address：	818 Renmin Road, Wuling District, Changde City, Hunan Province

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 co.Ltd

研究疾病：

乳腺癌脑转移

Target disease：

Breast cancer, Brain metastases

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：

4

研究设计：

随机平行对照

Study design：

Parallel

研究目的：

探索SHR-A1811单药或联合帕妥珠单抗治疗吡咯替尼经治进展的HER2阳性晚期乳腺癌脑转移患者疗效和安全性

Objectives of Study：

To explore the efficacy and safety of SHR-A1811 or in combination with pertuzumab in the treatment of patients with HER2-positive advanced breast cancer with brain metastases after progression with pyrotinib

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 years;
2.Advanced breast cancer patients with positive HER-2 expression confirmed by pathology;  Note: HER2 positivity refers to the presence of at least 3+ immunohistochemical staining or FISH positivity in the pathological examination/review of primary or metastatic lesions performed by the Department of Pathology of the participating hospitals.
3.MRI was used to diagnose the reported brain metastases
4.In the advanced stage, brain metastasis occurred during the treatment with pyrotinib-containing regimen or progressed after the treatment with pyrotinib-containing regimen
5.In the advanced stage, the number of treatment lines was ≤2
6.The interval from previous therapy was more than 2 weeks, and acute toxicity from previous therapy had to resolve to grade 1 or less.
7.Previous radiation therapy for brain metastases was allowed
8.The use of mannitol, bevacizumab, or hormone therapy was allowed before enrollment, provided that the dose was stable for at least a week without the need for an increment.
9.The predicted survival time was ≥3 months.
10.Vital organ function was defined as: absolute neutrophil count (ANC) ≥1.5×109/L Platelet count ≥100×109/L (100,000/mm3) Hemoglobin (Hgb) ≥90g/L (9.0 g/dL) Albumin level, ≥3.0 g/dL Total bilirubin ≤1.5×ULN Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN (≤5×ULN in patients with liver metastases) Serum creatinine ≤1.5×ULN or creatinine clearance ≥60 mL/ minute (calculated according to the Cockcroft-Gault formula, Annex 4) Prothrombin time (PT) and activated partial thromboplastin time (APTT) ≤1.5×ULN QTcF≤470 msec Echocardiography (ECHO) or cardiac radionuclide scan (MUGA) shows left ventricular ejection fraction (LVEF) ≥50%.
11.Patients or their legal representatives provided consent and signed informed consent and were willing and able to comply with the scheduled visits, study treatment plan, laboratory tests, and other trial procedures.

排除标准：

1. 合并广泛软脑膜转移且用激素脱水治疗效果不佳的脑转移患者； 2. 存在无法通过引流或其他方法控制的第三间隙积液（如大量胸水和腹水）； 3. 入组前 4 周内接受过化疗、重大手术或分子靶向治疗者；入组前 2 周内接受过内分泌治疗；入组前 6 周内接受过亚硝基脲或丝裂霉素化疗； 4. 入组前 4 周内参加过其它新药临床试验； 5. 既往接受过含拓扑异构酶I抑制剂的抗HER2-ADC 6. 既往 5 年内患有其他恶性肿瘤，不包括已治愈的宫颈原位癌、皮肤基底细胞癌或皮肤鳞状细胞癌； 7. 同时接受其他任何抗肿瘤治疗，贝伐珠单抗控制脑水肿和双膦酸盐治疗骨转移或预防骨质疏松是例外； 8. 首次用药前2周内使用过免疫抑制剂或全身激素治疗以达到免疫抑制目的者（剂量>10 mg/d泼尼松或同等药物生理学剂量的其他皮质类固醇激素），不包括鼻喷或吸入性皮质类固醇激素。 9. 患者存在任何活动性自身免疫病或有自身免疫疾病史且可能复发[包括但不局限于：自身免疫性肝炎、葡萄膜炎、肠炎、垂体炎、血管炎、肾炎、甲状腺功能亢进、甲状腺功能减退（仅通过激素替代治疗可以控制的受试者可纳入）]；受试者患有无需系统治疗的皮肤病如白癜风、银屑病、脱发，接受胰岛素治疗的经控制的I型糖尿病或在童年期哮喘已完全缓解，成人后无需任何干预的可纳入；需要支气管扩张剂进行医学干预的哮喘患者则不能纳入。 10. 有免疫缺陷病史，包括HIV检测阳性，其他获得性、先天性免疫缺陷疾病，或有器官移植史。 11. 存在有临床意义的心血管疾病，如重度/不稳定型心绞痛、有症状的充血性心力衰竭（NYHA ≥Ⅱ级）、有临床意义且需治疗或干预的室上性或室性心律失常、首次用药前6个月内发生过心肌梗死、脑血管意外（包括一过性脑缺血发作）。 12.未得到控制的高血压（静息状态下：收缩压＞160 mmHg或舒张压＞100 mmHg）； 13. 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或在整个试验期间不愿意采取有效避孕措施的育龄女性患者。 14.已知或可疑有间质性肺炎的受试者；首次给药前三个月内存在其他可能干扰药物相关肺毒性检测或处理的、严重影响呼吸功能的中重度肺部疾病，包括但不限于特发性肺组织纤维化、机化性肺炎/闭塞性细支气管炎、肺栓塞、严重哮喘、严重慢性阻塞性肺疾病（COPD）、阻塞性/限制性肺病等；以及任何肺部受累的自身免疫性、结缔组织或炎症性疾病，例如类风湿性关节炎、干燥综合症、结节病等，或既往接受过全肺切除手术等。既往接受免疫检查点抑制剂治疗期间发生过≥3级间质性肺炎的受试者不允许入组本研究。 15. 已知存在的遗传性或获得性出血倾向（如血友病、凝血功能障碍等）。 16. 存在活动性乙型肝炎（HBsAg阳性且HBV DNA≥500 IU/mL）、丙型肝炎（丙肝抗体阳性且HCV RNA高于正常值范围上限）、肝硬化；或需要抗生素、抗病毒药或抗真菌药控制的严重感染者。 17. 既往抗肿瘤治疗导致的毒性尚未恢复至≤ Ⅰ 级者（脱发除外；根据研究者的判断，经与申办方协商后，部分可耐受的慢性Ⅱ级毒性可除外）。 18. 已知对任一研究药物或其任何辅料过敏，或对人源化单克隆抗体产品（如曲妥珠单抗、帕妥珠单抗等）过敏者。 19. 存在其他严重身体或精神疾病或实验室检查异常，可能增加参与研究的风险，或干扰研究结果，以及研究者认为不适合参与本研究的患者。 20. 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.Brain metastasis patients with extensive leptomeningeal metastasis and poor response to hormone dehydration treatment; 2.The presence of third-space fluid collection (e.g., massive pleural effusion and ascites) that cannot be controlled by drainage or other methods; 3.Patients who received chemotherapy, major surgery or molecular targeted therapy within 4 weeks before enrollment; Patients received endocrine therapy within 2 weeks before enrollment. Chemotherapy with nitrosourea or mitomycin was administered within 6 weeks before enrollment. 4.Participated in other clinical trials of new drugs within 4 weeks before enrollment; 5.had previously received anti-HER2-ADC containing a topoisomerase I inhibitor 6.Other malignant tumors in the past 5 years, excluding cured cervical carcinoma in situ, skin basal cell carcinoma or skin squamous cell carcinoma; 7.The exceptions were concomitant use of any other antineoplastic therapy, bevacizumab for the control of brain edema and bisphosphonates for the treatment of bone metastases or the prevention of osteoporosis. 8.Patients who had used immunosuppressive or systemic hormonal therapy for immunosuppression within 2 weeks before the first dose (prednisone at a dose of >10 mg per day or another corticosteroid at the pharmacologic physiological dose) did not include nasal spray or inhaled corticosteroids 9.Patients have any active autoimmune disease or a history of autoimmune disease that may recur (including but not limited to: autoimmune hepatitis, uveitis, enteritis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism (those controlled only with hormone replacement therapy are eligible); Subjects with skin diseases requiring no systemic treatment such as vitiligo, psoriasis, alopecia, controlled type I diabetes treated with insulin, or asthma that had been completely resolved in childhood and without any intervention in adulthood were included. Patients with asthma who required medical intervention with bronchodilators were excluded. 10.A history of immunodeficiency, including testing positive for HIV, other acquired or congenital immunodeficiency disorders, or a history of organ transplantation. 11.The presence of clinically significant cardiovascular disease, such as severe/unstable angina, symptomatic congestive heart failure (NYHA class ≥ II), clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention, myocardial infarction within 6 months before the first dose of medication, or cerebrovascular accident (including transient ischemic attack)." 12.Uncontrolled hypertension (resting systolic blood pressure > 160 mmHg or diastolic blood pressure > 100 mmHg); 13.Pregnant, lactating, fertile women who had a positive pregnancy test at baseline, or women of childbearing age who were unwilling to use effective contraception throughout the trial. 14.Subjects with known or suspected interstitial pneumonia; Other moderate to severe pulmonary diseases that may interfere with the detection or treatment of drug-related pulmonary toxicity and seriously affect respiratory function within three months before the first dose, including but not limited to idiopathic pulmonary fibrosis, organizing pneumonia/bronchiolitis obliterans, pulmonary embolism, severe asthma, severe chronic obstructive pulmonary disease (COPD), obstructive/restrictive pulmonary disease, etc. "And any autoimmune, connective tissue, or inflammatory disease with lung involvement, such as rheumatoid arthritis, Sjogren's syndrome, sarcoidosis, or previous pneumonectomy." Participants who had had interstitial pneumonia of grade 3 or higher while receiving previous treatment with an immune checkpoint inhibitor were not allowed to participate. 15.Known inherited or acquired bleeding tendency (e.g., hemophilia, coagulopathy, etc.)." 16.Patients with active hepatitis B (HBsAg positive and HBV DNA≥500 IU/mL), hepatitis C (hepatitis C antibody positive and HCV RNA higher than the upper limit of the normal range), cirrhosis; Or severely ill patients requiring control with antibiotics, antiviral or antifungal drugs. 17.Patients who have not recovered to grade I or less toxicity from previous antineoplastic therapy (except alopecia; At the discretion of the investigator and in consultation with the sponsor, some tolerable chronic grade II toxicity was excluded.) 18.Known allergy to either study drug or any of its excipients, or to humanized monoclonal antibody products (e.g., trastuzumab, pertuzumab, etc.). 19.The presence of other serious physical or mental illnesses or laboratory abnormalities that may increase the risk of participating in the study, or interfere with the results of the study, and patients who were deemed by the investigators to be unsuitable for participation in the study. 20.The patient was considered by the investigator to be ineligible for participation in the study for any other condition.

研究实施时间：

Study execute time：

从 From 2025-09-01 00:00:00至 To 2027-09-01 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2025-09-01 00:00:00 至 To 2026-12-31 00:00:00

干预措施：

Interventions：

组别：	A	样本量：	20
Group：	Group A	Sample size：	20
干预措施：	SHR-A1811	干预措施代码：
Intervention：	SHR-A1811	Intervention code：

组别：	B	样本量：	20
Group：	Group B	Sample size：	20
干预措施：	SHR-A1811+帕妥珠单抗	干预措施代码：
Intervention：	SHR-A1811+Pertuzumab	Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：	中国	省(直辖市)：	湖南	市(区县)：
Country：	China	Province：	Hunan	City：
单位(医院)：	常德市第一人民医院	单位级别：	三甲
Institution hospital：	Changde First People's Hospital	Level of the institution：	Tertiary

国家：	中国	省(直辖市)：	湖南	市(区县)：
Country：	China	Province：	Hunan	City：
单位(医院)：	娄底市中心医院	单位级别：	三甲
Institution hospital：	Loudi Central Hospital	Level of the institution：	Tertiary

国家：	中国	省(直辖市)：	湖南	市(区县)：
Country：	China	Province：	Hunan	City：
单位(医院)：	永州市中心医院	单位级别：	三甲
Institution hospital：	Yongzhou Central Hospital	Level of the institution：	Tertiary

国家：	中国	省(直辖市)：	湖南	市(区县)：
Country：	China	Province：	Hunan	City：
单位(医院)：	岳阳市中心医院	单位级别：	三甲
Institution hospital：	Yueyang Central Hospital	Level of the institution：	Tertiary

国家：	中国	省(直辖市)：	湖南	市(区县)：
Country：	China	Province：	Hunan	City：
单位(医院)：	益阳市中心医院	单位级别：	三甲
Institution hospital：	Yiyang Central Hospital	Level of the institution：	Tertiary

测量指标：

Outcomes：

指标中文名：	颅内客观缓解率	指标类型：	主要指标
Outcome：	IC-ORR	Type：	Primary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	无疾病进展生存期	指标类型：	次要指标
Outcome：	PFS	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：	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：	颅内中枢神经系统无进展生存期	指标类型：	次要指标
Outcome：	IC-PFS	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：	脑脊液	组织：
Sample Name：	Cerebrospinal fluid	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：	肿瘤组织	组织：
Sample Name：	Tumor tissue	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）：

简单随机

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

Simple randomize

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：	无
Blinding：	none
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）：	向研究作者索取
The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：	Ask for investigator
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
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：	无/No
注册人： Name of Registration：	2025-08-29 17:16:20