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：	ChiCTR2500112844
最近更新日期： Date of Last Refreshed on：	2025-11-20 09:02:13
注册时间： Date of Registration：	2025-11-20 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	曲妥珠单抗联合化疗和来氟米特治疗HER-2表达的不可切除晚期胆道恶性肿瘤：一项单臂开放性前瞻性II期临床研究
Public title：	Trastuzumab Combined With Chemotherapy and Leflunomide for HER2-Expressing Unresectable Advanced Biliary Tract Malignancies: An Open-Label, Single-Arm, Phase II Study
注册题目简写：
English Acronym：
研究课题的正式科学名称：	曲妥珠单抗联合化疗和来氟米特治疗HER-2表达的不可切除晚期胆道恶性肿瘤：一项单臂开放性前瞻性II期临床研究
Scientific title：	Trastuzumab Combined With Chemotherapy and Leflunomide for HER2-Expressing Unresectable Advanced Biliary Tract Malignancies: An Open-Label, Single-Arm, Phase II Study
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：	冯飞灵	研究负责人：	冯飞灵
Applicant：	Feng Feiling	Study leader：	Feng Feiling
申请注册联系人电话： Applicant telephone：	+86 13818611858	研究负责人电话： Study leader's telephone：	+86 21 81887562
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：	ffeiling@163.com	研究负责人电子邮件： Study leader's E-mail：	ffeiling@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：	中国上海市杨浦区长海路225号	研究负责人通讯地址：	中国上海市杨浦区长海路225号
Applicant address：	225 Changhai Road, Yangpu District, Shanghai, China	Study leader's address：	225 Changhai Road, Yangpu District, Shanghai, 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：	海军军医大学第三附属医院(上海东方肝胆外科医院)
Applicant's institution：	The Third Affiliated Hospital of Naval Medical University (Shanghai Eastern Hepatobiliary Surgery Hospital)
研究负责人所在单位：	海军军医大学第三附属医院(上海东方肝胆外科医院)
Affiliation of the Leader：	The Third Affiliated Hospital of Naval Medical University (Shanghai Eastern Hepatobiliary Surgery Hospital)

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：	EHBHKY2025-H23-P001	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：	海军军医大学第三附属医院医学伦理委员会
Name of the ethic committee：	Medical Ethics Committee of the Third Hospital Affiliated to Naval Medical University
伦理委员会批准日期： Date of approved by ethic committee：	2025-09-18 00:00:00
伦理委员会联系人：	邰小云
Contact Name of the ethic committee：	Tai Xiaoyun
伦理委员会联系地址：	中国上海市杨浦区长海路225号
Contact Address of the ethic committee：	225 Changhai Road, Yangpu District, Shanghai, China
伦理委员会联系人电话： Contact phone of the ethic committee：	+86 21 81875703	伦理委员会联系人邮箱： Contact email of the ethic committee：	taixiaoyunlele@163.com

研究实施负责（组长）单位：

海军军医大学第三附属医院（上海东方肝胆外科医院）

Primary sponsor：

The Third Affiliated Hospital of Naval Medical University (Shanghai Eastern Hepatobiliary Surgery Hospital)

研究实施负责（组长）单位地址：

中国上海市杨浦区长海路225号

Primary sponsor's address：

225 Changhai Road, Yangpu District, Shanghai, 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)：	上海	市(区县)：
Country：	China	Province：	Shanghai	City：
单位(医院)：	海军军医大学第三附属医院（上海东方肝胆外科医院）	具体地址：	中国上海市杨浦区长海路225号
Institution hospital：	The Third Affiliated Hospital of Naval Medical University (Shanghai Eastern Hepatobiliary Surgery Hospital)	Address：	225 Changhai Road, Yangpu District, Shanghai, China

经费或物资来源：

自选课题（自筹）

Source(s) of funding：

Self-funded

研究疾病：

胆道恶性肿瘤

Target disease：

Biliary tract cancer

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：

II期临床试验

Study phase：

2

研究设计：

单臂

Study design：

Single arm

研究目的：

旨在评估曲妥珠单抗联合化疗和来氟米特二线治疗HER2表达晚期胆道癌的安全性和有效性

Objectives of Study：

This single-arm, phase II clinical study aims to evaluate the safety and efficacy of trastuzumab in combination with chemotherapy and Leflunomide as second-line therapy in patients with advanced HER2-expressing biliary tract cancer who have progressed following prior standard first-line treatment.

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. 在任何试验相关流程实施之前，签署书面知情同意；  
2. 男或女性>=18 周岁，<=75 周岁；  
3. 经组织学或细胞学证实的不可手术的局部晚期或转移性胆道肿瘤，包括肝内胆管癌、肝外胆管癌和胆囊癌；  
4. 既往接受一线标准系统性治疗后进展，即在一线标准治疗期间或距离末次治疗6个月内出现符合RECIST v1.1标准的疾病进展；  
5. 经检测 HER2 阳性或 HER2 低表达：HER2 阳性定义为 IHC 检测结果 3+，或 IHC 检测结果 2+且 FISH 方法确认 HER2 基因扩增阳性，HER2 低表达定义为：标准免疫组化(IHC)检测为 1+，2+/FISH-；  
6. 预期生存时间>=3 个月；  
7. 根据 RECIST1.1 标准至少有 1 个可测量病灶；  
8. ECOG PS 评分为 0-1；  
9. 足够器官功能，受试者需满足如下实验室指标：  
(1) 近 14 天未使用粒细胞集落刺激因子的情况下，中性粒细胞绝对值（ANC）>=1.5x10^9/L；  
(2) 近 14 天未输血的情况下，血小板>=90×10^9/L；  
(3) 近 14 天内无输血或使用促红细胞生成素的情况下，血红蛋白>=9g/dL；  
(4) 总胆红素<=1.5×正常值上限（ULN）；  
版本：V1.0 ，版本日期：20250328  
(5) 天门冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）在<=2.5×ULN（有肝转移的患者允许 ALT 或 AST <=5×ULN）；  
(6) 血肌酐 <=1.5 × ULN 并且肌酐清除率（采用 Cockcroft-Gault 公式计算）>=60 ml/min；  
(7) 凝血功能良好，定义为国际标准化比值（INR）或凝血酶原时间（PT）<=1.5 倍 ULN；  
(8) 甲状腺功能正常，定义为促甲状腺激素（TSH）在正常范围内。如基线 TSH 超出正常范围，如果总 T3（或 FT3）及 FT4 在正常范围内的受试者亦可入组；  
(9) 心肌酶谱在正常范围内（如研究者综合判断为不具有临床意义的单纯实验室异常也允许入组）；  
10. 左心室射血分数 (LVEF) >=50% 或高于机构正常范围的下限，以较低者为准；  
11. 对于育龄期女性受试者，应在接受首次研究药物给药（第 1 周期第 1 天）之前的 3 天内接受尿液或血清妊娠试验且结果为阴性。如果尿液妊娠试验结果无法确认为阴性，则要求进行血液妊娠试验。非育龄期女性定义为绝经后至少１年，或进行过手术绝育或子宫切除术；  
12. 如存在受孕风险，所有受试者（不论男性或女性）均需在整个治疗期间直至治疗末次研究药物给药后120 天内采用年失败率低于 1%的避孕措施；

Inclusion criteria

1. Written informed consent must be signed before any trial-related procedures are implemented.  
2. Male or female aged >=18 years and <=75 years.  
3. Histologically or cytologically confirmed unresectable locally advanced or metastatic biliary tract cancer, including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer.  
4. Disease progression after receiving first-line standard systemic therapy, defined as progression occurring during first-line standard therapy or within 6 months after the last treatment, according to RECIST v1.1 criteria.  
5. HER2-positive or HER2-low expression confirmed by testing: HER2-positive is defined as IHC 3+, or IHC 2+ with FISH confirmation of HER2 gene amplification; HER2-low expression is defined as standard immunohistochemistry (IHC) showing 1+, or 2+/FISH-negative.  
6. Expected survival time >=3 months.  
7. At least one measurable lesion according to RECIST v1.1 criteria.  
8. ECOG PS score of 0-1.  
9. Adequate organ function, with subjects meeting the following laboratory criteria:  
   (1) Absolute neutrophil count (ANC) >=1.5x10^9/L without granulocyte colony-stimulating factor (G-CSF) use within the past 14 days;  
   (2) Platelets >=90x10^9/L without blood transfusion within the past 14 days;  
   (3) Hemoglobin >=9g/dL without blood transfusion or erythropoietin use within the past 14 days;  
   (4) Total bilirubin <=1.5 times the upper limit of normal (ULN);  
   (5) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <=2.5x ULN (for patients with liver metastasis, ALT or AST <=5x ULN is permitted);  
   (6) Serum creatinine <=1.5x ULN and creatinine clearance (calculated using the Cockcroft-Gault formula) >=60 ml/min;  
   (7) Normal coagulation function, defined as international normalized ratio (INR) or prothrombin time (PT) <=1.5x ULN;  
   (8) Normal thyroid function, defined as thyroid-stimulating hormone (TSH) within normal range; if baseline TSH is outside normal range, subjects with total T3 (or FT3) and FT4 within normal range may also be enrolled;  
   (9) Normal myocardial enzyme profile (subjects with isolated laboratory abnormalities deemed not clinically significant by the investigator may also be enrolled).  
10. Left ventricular ejection fraction (LVEF) >=50% or above the lower limit of the institutional normal range, whichever is lower.  
11. For females of childbearing potential, a negative urine or serum pregnancy test must be performed within 3 days prior to the first dose of study drug (Day 1 of Cycle 1); if the urine pregnancy test result is indeterminate, a blood pregnancy test is required. Non-childbearing potential females are defined as those who are postmenopausal (amenorrheic for at least 1 year), or have undergone surgical sterilization or hysterectomy.  
12. All subjects with reproductive potential (regardless of gender) must use highly effective contraception with a failure rate of less than 1% per year throughout the treatment period and for 120 days after the last dose of study drug.

排除标准：

1. 首次给药前5年内诊断为胆道外的其他恶性疾病（不包括经过根治的皮肤基底细胞癌、皮肤鳞状上皮癌、和/或经过根治性切除的原位癌）； 2. 壶腹部肿瘤； 3. 当前正在参与干预性临床研究治疗，或在首次给药前4周内接受过其他研究药物或使用过研究器械治疗； 4. 首次给药前4周之内接受过针对胆道肿瘤的局部治疗如姑息性放疗。对于首次给药前4周前接受放射治疗的患者，必须满足下述所有条件方可入组： (1) 目前不存在任何放疗相关的毒性反应； (2) 不需要服用糖皮质激素； (3) 排除放射性肝炎、放射性肠炎等； 5. 首次给药前2周内接受过具有抗肿瘤适应症的中成药或免疫调节作用的药物（包括胸腺肽、干扰素、白介素，除外为控制胸水局部使用）系统性全身治疗； 6. 首次给药前2年内发生过需要全身性治疗（例如使用缓解疾病药物、糖皮质激素或免疫抑制剂）的活动性自身性免疫疾病。补充说明： (1) 替代疗法（例如甲状腺素、胰岛素或者用于肾上腺或垂体机能不全的生理性糖皮质激素等）不视为全身性治疗； (2) 已知的原发性免疫缺陷病史； (3) 仅存在自身免疫抗体阳性的患者需根据研究者判断确认是否存在自身免疫性疾病； 7. 研究首次给药前4周内正在接受全身性糖皮质激素治疗（不包括喷鼻、吸入性或其他途径的局部糖皮质激素）或任何其他形式的免疫抑制疗法； (1) 注：允许使用生理剂量的糖皮质激素（<=10 mg/天的泼尼松或等效药物）； 8. 存在临床上不可控制的胸腔积液/腹腔积液（不需要引流积液或停止引流3天积液无明显增加的患者可以入组）； 9. 已知异体器官移植（角膜移植除外）或异体造血干细胞移植； 10. 已知对本研究药物活性成分或辅料过敏者； 11. 具有影响口服药物的多种因素（比如无法吞咽、胃肠道切除术后、慢性腹泻和肠梗阻等）者； 12. 在开始治疗前，尚未从任何干预措施引起的毒性和/或并发症中充分恢复（即，<=1级或达到基线，不包括乏力或脱发）； 13. 已知人类免疫缺陷病毒（HIV）感染史（即HIV 1/2抗体阳性）； 14. 未经治疗的活动性乙肝（定义为HBsAg阳性同时检测到HBV-DNA拷贝数大于所在研究中心检验科正常值上限）；注：符合下列标准的乙肝受试者亦可入组：（1) 首次给药前HBV病毒载量<2.5×10^3拷贝/ml（500 IU/ml），受试者应在整个研究治疗期间接受抗HBV治疗；（2) 对于抗HBc（+）、HBsAg（-）、抗HBs（-）和HBV病毒载量（-）的受试者，不需要接受预防性抗HBV治疗，但是需要密切监测病毒再激活； 15. 活动性的HCV感染受试者（HCV抗体阳性且HCV-RNA水平高于检测下限）； 16. 首次给药前4周内接种过减毒活疫苗； 17. 妊娠或哺乳期妇女； 18. 存在任何严重或不能控制的全身性疾病，例如： (1) 静息心电图在节律、传导或形态上出现有重大且症状严重难以控制的异常，如完全性左束支传导阻滞，II度以上心脏传导阻滞，室性心律失常或心房颤动； (2) 不稳定型心绞痛，充血性心力衰竭，纽约心脏病协会（NYHA）分级>=2级的慢性心衰； (3) 在入选治疗前6个月内发生过任何动脉血栓、栓塞或缺血，如心肌梗死、不稳定型心绞痛、脑血管意外或一过性脑缺血发作等； (4) 首次给药前4周之内接受过重大的外科手术（开颅、开胸或开腹手术）或者未愈合的伤口、溃疡或骨折。首次给药之前7天内接受过组织穿刺活检或其他小外科手术，以静脉输液为目的的静脉穿刺置管除外； (5) 血压控制不理想（收缩压>140 mmHg，舒张压>90 mmHg）； (6) 活动性肺结核； (7) 存在需要全身性治疗的活动性或未能控制的感染； (8) 存在临床活动性憩室炎、腹腔脓肿、胃肠道梗阻； (9) 肝脏疾病如肝硬化、失代偿性肝病、急性或慢性活动性肝炎； (10) 糖尿病控制不佳（空腹血糖（FBG）>10mmol/L）； (11) 尿常规提示尿蛋白>=++，且证实24小时尿蛋白定量>1.0 g者； (12) 存在精神障碍且无法配合治疗的患者； 19. 有可能干扰试验结果、妨碍受试者全程参与研究的病史或疾病证据、治疗或实验室检查值异常，或研究者认为其他不适合入组的情况，研究者认为存在其他潜在风险不适合参加本研究；

Exclusion criteria：

1. Diagnosis of any other malignancy outside the biliary tract within 5 years prior to first dose (excluding adequately treated basal cell carcinoma, squamous cell carcinoma of the skin, and/or in situ carcinoma after radical resection); 2. Ampullary tumor; 3. Currently participating in an interventional clinical study, or received other investigational drugs or used investigational devices within 4 weeks prior to first dose; 4. Received local therapy for biliary tract tumors, such as palliative radiotherapy, within 4 weeks prior to first dose. For patients who received radiotherapy more than 4 weeks prior to first dose, the following criteria must all be met for enrollment: (1) No ongoing radiation-related toxicities; (2) No requirement for corticosteroid use; (3) Exclusion of radiation hepatitis, radiation enteritis, etc.; 5. Received systemic systemic therapy with traditional Chinese medicine or immunomodulatory agents with anti-tumor indications (including thymosin, interferon, interleukin, except local use for controlling pleural effusion) within 2 weeks prior to first dose; 6. History of active autoimmune disease requiring systemic treatment (e.g., disease-modifying drugs, corticosteroids, or immunosuppressants) within 2 years prior to first dose. Note: (1) Replacement therapies (e.g., thyroid hormone, insulin, or physiological-dose corticosteroids for adrenal or pituitary insufficiency) are not considered systemic treatment; (2) History of known primary immunodeficiency; (3) Patients with only positive autoantibodies must be evaluated by the investigator to confirm presence of autoimmune disease; 7. Receiving systemic corticosteroid therapy or any other form of immunosuppressive therapy within 4 weeks prior to first dose (excluding intranasal, inhaled, or other local corticosteroids); (1) Note: Physiological-dose corticosteroids (<=10 mg/day prednisone or equivalent) are permitted; 8. Clinically uncontrolled pleural or peritoneal effusion (patients who do not require drainage or whose effusion does not significantly increase within 3 days after drainage cessation may be enrolled); 9. History of allogeneic organ transplantation (except corneal transplantation) or allogeneic hematopoietic stem cell transplantation; 10. Known hypersensitivity to the active ingredient or excipients of the study drug; 11. Conditions affecting oral drug absorption, such as dysphagia, post-gastrointestinal resection, chronic diarrhea, or intestinal obstruction; 12. Inadequate recovery from toxicity and/or complications of any prior intervention prior to initiation of treatment (i.e., <= Grade 1 or back to baseline, excluding fatigue or alopecia); 13. Known history of human immunodeficiency virus (HIV) infection (i.e., HIV-1/2 antibody positive); 14. Untreated active hepatitis B (defined as HBsAg-positive with HBV-DNA copy number exceeding the upper limit of normal in the local laboratory); Note: Hepatitis B patients meeting the following criteria may be enrolled: (1) HBV viral load <2.5×10^3 copies/mL (500 IU/mL) at first dose; patients must receive anti-HBV therapy throughout the study period; (2) Patients who are anti-HBc-positive, HBsAg-negative, anti-HBs-negative, and HBV-DNA-negative do not require prophylactic anti-HBV therapy but require close monitoring for viral reactivation; 15. Active HCV infection (HCV antibody-positive with HCV-RNA level above the lower limit of detection); 16. Received live attenuated vaccine within 4 weeks prior to first dose; 17. Pregnant or lactating women; 18. Presence of any severe or uncontrolled systemic disease, such as: (1) Significant and poorly controlled abnormalities on resting ECG in rhythm, conduction, or morphology, such as complete left bundle branch block, second-degree or higher heart block, ventricular arrhythmias, or atrial fibrillation; (2) Unstable angina, congestive heart failure, NYHA class >=2 chronic heart failure; (3) Any arterial thrombotic, embolic, or ischemic event within 6 months prior to treatment initiation, such as myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack; (4) Major surgery (craniotomy, thoracotomy, or laparotomy) within 4 weeks prior to first dose, or unhealed wounds, ulcers, or fractures. Minor surgical procedures (e.g., tissue biopsy) within 7 days prior to first dose are permitted, except for venous catheter placement for intravenous infusion; (5) Poorly controlled blood pressure (systolic >140 mmHg, diastolic >90 mmHg); (6) Active tuberculosis; (7) Active or uncontrolled infection requiring systemic treatment; (8) Clinically active diverticulitis, abdominal abscess, or gastrointestinal obstruction; (9) Liver disease such as cirrhosis, decompensated liver disease, acute or chronic active hepatitis; (10) Poorly controlled diabetes mellitus (fasting blood glucose [FBG] >10 mmol/L); (11) Urinalysis showing proteinuria >=++, with confirmed 24-hour urinary protein excretion >1.0 g; (12) Patients with psychiatric disorders who are unable to comply with treatment; 19. Any other history, disease, treatment, or laboratory abnormality that may interfere with trial outcomes or impede full participation in the study, or any other condition deemed by the investigator to pose potential risks and render the subject unsuitable for enrollment.

研究实施时间：

Study execute time：

从 From 2025-09-18 00:00:00至 To 2028-09-30 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2025-11-20 00:00:00 至 To 2027-12-31 00:00:00

干预措施：

Interventions：

组别：	试验组	样本量：	53
Group：	Experiment Group	Sample size：	53
干预措施：	曲妥珠单抗+化疗+来氟米特。采用 Simon 两阶段设计，第一阶段需要入组 13 例有效受试者，若>5 例患者达到 ORR，则进行第二阶段入组，总共需要 43 例有效受试者（HER2阳性）。对于 HER2 低表达患者，计划纳入～10-20 例受试者。因考虑到执行过程中，研究者可能根据初步疗效和安全性数据进一步扩大入组例数，故实际入组例数与计划入组例数可能不同。	干预措施代码：
Intervention：	Trastuzumab + chemotherapy + leflunomide. Simon's two-stage design is employed. The first stage requires enrolling 13 evaluable subjects; if more than 5 patients achieve ORR (Objective Response Rate), proceed to the second stage enrollment, with a total of 43 evaluable subjects needed for HER2-positive patients. For HER2-low expression patients, approximately 10 to 20 subjects are planned for enrollment. Given that during trial execution, investigators may further expand enrollment based on preliminary efficacy and safety data, the actual number of enrolled subjects may differ from the planned number.	Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：	中国	省(直辖市)：	上海	市(区县)：
Country：	China	Province：	Shanghai	City：
单位(医院)：	海军军医大学第三附属医院（上海东方肝胆外科医院）	单位级别：	三级甲等
Institution hospital：	The Third Affiliated Hospital of Naval Medical University (Shanghai Eastern Hepatobiliary Surgery Hospital)	Level of the institution：	Tertiary A

测量指标：

Outcomes：

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：	总生存期将通过根据研究方案安排的随访访视进行检测，直至患者死亡或研究结束
Measure time point of outcome：		Measure method：	Overall survival will be monitored through scheduled follow-up visits as per the study protocol until death or the end of the study

指标中文名：	持续缓解率	指标类型：	次要指标
Outcome：	Duration of Response	Type：	Secondary indicator
测量时间点：		测量方法：	RECIST v1.1
Measure time point of outcome：		Measure method：	RECIST v1.1

指标中文名：	无进展生存期	指标类型：	次要指标
Outcome：	Progression-free Survival	Type：	Secondary indicator
测量时间点：		测量方法：	RECIST v1.1
Measure time point of outcome：		Measure method：	RECIST v1.1

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：	NCI-CTCAE v5.0.
Measure time point of outcome：		Measure method：	NCI-CTCAE v5.0.

指标中文名：	疾病控制率	指标类型：	次要指标
Outcome：	Disease Control Rate	Type：	Secondary indicator
测量时间点：		测量方法：	RECIST v1.1
Measure time point of outcome：		Measure method：	RECIST v1.1

指标中文名：	客观缓解率	指标类型：	主要指标
Outcome：	Objevtive Response Rate	Type：	Primary indicator
测量时间点：		测量方法：	RECIST v1.1
Measure time point of outcome：		Measure method：	RECIST v1.1

采集人体标本：

Collecting sample(s)
from participants：

标本中文名：	无	组织：
Sample Name：	NA	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	75	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)：

None

是否公开试验完成后的统计结果:

Calculated Results after the Study Completed public access:

不公开/Private

盲法：	无
Blinding：	None

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）：	无
The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：	None
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：	Case Record Form
数据与安全监察委员会： Data and Safety Monitoring Committee：	无/No
注册人： Name of Registration：	2025-11-20 09:02:13