ChiCTR2500115410 版本V1.0 版本创建时间2025/12/25 15:31:39 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：

ChiCTR2500115410 

最近更新日期：

Date of Last Refreshed on：

2025-12-25 15:31:16 

注册时间：

Date of Registration：

2025-12-25 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

HIPEC联合CRS和度伐利尤单抗治疗胆道肿瘤伴腹膜转移的单臂 II期临床研究

Public title：

A single-arm phase II clinical trial of HIPEC in combination with CRS and durvalumab for the treatment of biliary tract tumors with peritoneal metastases

注册题目简写：

English Acronym：

研究课题的正式科学名称：

HIPEC联合CRS和度伐利尤单抗治疗胆道肿瘤伴腹膜转移的单臂 II期临床研究

Scientific title：

A single-arm phase II clinical trial of HIPEC in combination with CRS and durvalumab for the treatment of biliary tract tumors with peritoneal metastases

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：

Feiling Feng 

Study leader：

Feiling Feng 

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 8188 7562

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：

中国上海市嘉定区墨玉北路700号

研究负责人通讯地址：

中国上海市嘉定区墨玉北路700号

Applicant address：

No. 700, Mo Yu North Road, Jiading District, Shanghai, China

Study leader's address：

No. 700, Mo Yu North Road, Jiading 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

Applicant's institution：

The Third Affiliated Hospital of Naval Medical University

研究负责人所在单位：

海军军医大学第三附属医院

Affiliation of the Leader：

The Third Affiliated Hospital of Naval 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：

EHBHKY2025-H022-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：

中国上海市嘉定区墨玉北路700号

Contact Address of the ethic committee：

No. 700, Mo Yu North Road, Jiading 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

Primary sponsor：

The Third Affiliated Hospital of Naval Medical University

研究实施负责（组长）单位地址：

中国上海市嘉定区墨玉北路700号

Primary sponsor's address：

No. 700, Mo Yu North Road, Jiading 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

市(区县)：

Country：

China

Province：

Shanghai

City：

单位(医院)：

海军军医大学第三附属医院

具体地址：

中国上海市嘉定区墨玉北路700号

Institution
hospital：

The Third Affiliated Hospital of Naval Medical University

Address：

No. 700, Mo Yu North Road, Jiading District, Shanghai, China

经费或物资来源：

自选课题（自筹）

Source(s) of funding：

Investigator-initiated

Target disease：

Biliary tract cancer

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：

单臂 

Study design：

Single arm 

研究目的：

评价HIPEC联合CRS和度伐利尤单抗治疗胆道肿瘤伴腹膜转移的安全性及有效性。  

Objectives of Study：

Evaluate the safety and efficacy of HIPEC combined with CRS and durvalumab in the treatment of biliary tract cancer with peritoneal metastases.

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.经组织学证实的不可切除的晚期或转移性伴有腹膜转移的胆道肿瘤患者（包括胆管癌和胆囊癌）； 2.初次诊断时患不可切除或转移性 BTC 且既往未接受过治疗的 BTC 患者。 3.允许患者既往接受过根治性治疗（手术以及在辅助治疗中给予的化疗和/或放疗），且疾病复发>6 个月。包括术后有残余病灶且接受了化疗、化疗栓塞或放疗的患者。 4.入选时世界卫生组织 (WHO)/ECOG 体能状态评分 (PS) 为 0 或 1（术前卡氏体能状态评分 (KPS) 70 分）； 5.基线时至少有 1 个病灶符合 RECIST 1.1 靶病灶 (TL)。 6.HBV 感染（特征为按照当地实验室标准，HBsAg 阳性和/或抗 HBcAb 阳性，且可检出HBV DNA）的患者必须按照机构惯例接受抗病毒治疗，以确保在纳入前获得充分的病毒抑制（根据当地实验室标准）。受试者在研究期间及接受研究干预治疗末次给药后 6个月后需继续接受抗病毒治疗。对于抗 HBc 检测阳性但未检测出 HBV DNA（根据当地实验室标准）的患者，不要求在纳入研究前进行抗病毒治疗。这些受试者将在每个周期接受检测，以监测 HBV DNA 水平，并在检测到 HBV DNA 后开始抗病毒治疗（根据当地实验室标准）。可检测到 HBV DNA 的受试者在研究期间及接受研究干预治疗末次给药6 个月后必须开始且持续接受抗病毒治疗。 7.器官和骨髓功能良好：血红蛋白≥9.0 g/dL。 中性粒细胞绝对计数≥1.5 × 109 /L。 血小板计数≥100 × 109/L。 8.血清胆红素≤正常上限(ULN)的2.5倍。此条件不适用于患有经证实的 Gilbert 综合征患者。任何临床显著的胆道梗阻必须在入组研究前解除。对于肝转移患者，ALT 和 AST 应≤5 × ULN。 9.通过 Cockcroft-Gault（基于实际体重）公式或 24 小时尿肌酐清除率测定法计算的肌酐清除率应>50 mL/min。对于含顺铂、奥沙利铂或吉西他滨单药治疗的化疗方案，通过Cockcroft- Gault（基于实际体重）或24 小时尿肌酐清除率测定法计算的肌酐清除率的推荐阈值应>40 mL/min。 10.预期寿命至少为 12 周。

Inclusion criteria

1. Patients with histologically confirmed unresectable advanced or metastatic biliary tract tumors with peritoneal metastasis (including cholangiocarcinoma and gallbladder cancer); 2. Patients with BTC who had unresectable or metastatic BTC at the time of initial diagnosis and had not received prior treatment. 3. Patients who have received prior curative therapy (surgery and chemotherapy and/or radiotherapy given in adjuvant therapy) with disease recurrence > 6 months. Patients with residual lesions after surgery who have received chemotherapy, chemoembolization or radiotherapy are included. 4. World Health Organization (WHO)/ECOG performance status score (PS) of 0 or 1 (preoperative Carinthian performance status score (KPS) score of 70 at the time of inclusion; 5. At least 1 lesion compliant with RECIST 1.1 target lesion (TL) at baseline. 6. Patients with HBV infection (characterized by HBsAg positive and/or anti-HBcAb positive according to local laboratory standards with detectable HBV DNA) must receive antiviral therapy as per institutional practice to ensure adequate viral suppression (according to local laboratory standards) prior to inclusion. Subjects need to continue receiving antiviral therapy during the study and 6 months after receiving the last dose of study intervention. Antiviral therapy prior to inclusion in the study is not required for patients with a positive anti-HBc test but no detectable HBV DNA (according to local laboratory standards). These subjects will be tested at each cycle to monitor HBV DNA levels and to start antiviral therapy (according to local laboratory standards) after HBV DNA is detected. Subjects with detectable HBV DNA must start and continue antiviral therapy during the study and 6 months after receiving the last dose of study intervention. 7. Good organ and bone marrow function: hemoglobin>= 9.0 g/dL. Absolute neutrophil count >= 1.5 × 10^9 /L. Platelet count >= 100 × 10^9/L. 8. Serum bilirubin <= 2.5 times the upper limit of normal (ULN). This condition is not indicated in patients with proven Gilbert syndrome. Any clinically significant biliary obstruction must be resolved prior to enrollment in the study. For patients with liver metastases, ALT and AST should be <=5 × ULN. 9. Creatinine clearance calculated by the Cockcroft-Gault (based on actual body weight) formula or 24-hour urine creatinine clearance assay should be > 50 mL/min. For chemotherapy regimens containing cisplatin, oxaliplatin, or gemcitabine, the recommended threshold for creatinine clearance calculated by Cockcroft- Gault (based on actual body weight) or 24-hour urinary creatinine clearance assay should > 40 mL/min. 10. The expected lifespan is at least 12 weeks.

排除标准：

1.怀孕或哺乳期妇女，及育龄妇女在基线其进行妊娠试验结果阳性者；
2.通过CT/MR/PET-CT诊断中枢神经系统转移者；
3.先前接受过活疫苗接种或放疗等抗肿瘤治疗；
4.研究药物首次用药前4周内参加了或正在参加其他药物或疗法临床试验的患者；
5.研究药物首次用药前4周内接受了大型外科手术或尚未从此手术的副作用中恢复，研究药物首次用药前2周内进行过放疗的患者；
6.患者存在任何原发性免疫缺陷病、活动性自身免疫病或有自身免疫病病史，包括但不局限于：自身免疫性肝炎、间质性肺炎、葡萄膜炎、肠炎、肝炎、垂体炎、血管炎、肾炎、甲状腺功能亢进、白癜风，曾患哮喘的患者，在童年期哮喘已完全缓解，成年后无需任何干预的可纳入；患者需要支气管扩张剂进行医学干预的哮喘则不能纳入；
7.已知异体器官移植史和异体造血干细胞移植史的患者，以及正在使用免疫抑制剂或类固醇等激素治疗以达到免疫抑制目的（剂量>10mg/天泼尼松或其他等疗效激素），并在入组前2周内仍在继续使用的；
8.在过去的5 年中患有胆道系统恶性肿瘤以外的其他恶性肿瘤，已经治愈的皮肤基底细胞或鳞状细胞癌、浅表性膀胱癌、早期前列腺癌、原位宫颈癌或乳腺癌除外；
9.研究药物首次给药前1周内曾接受造血刺激因子,如接受粒细胞集落刺激因子(G-CSF)、促红细胞生成素等治疗的患者；
10.获得性免疫缺陷病毒(HIV)抗体或梅毒螺旋体抗体检测结果阳性，以及活动性乙型或丙型病毒性肝炎患者；
11.已知会对重组人源化PD-L1单克隆抗体药物及其组分过敏者；
12.入组前12个月内患有严重心血管疾病，例如临床症状明显的冠心病，NYHA≥II级的充血性心力衰竭，未控制的心律失常，心肌梗死；
13.首次用药前6个月内出现过如下情况: 深静脉血栓或肺栓塞;
心肌梗死;
严重或不稳定性心律失常或心绞痛;
经皮冠状动脉介入治疗、急性冠脉综合征、冠状动脉旁路移植术; 脑血管意外、短暂性脑缺血发作、脑栓塞。
14.接受过任何种类的胃肠道手术，或并发上消化道梗阻、出血、消化功能异常或吸收不良综合征，可能影响研究药物吸收者；
15.并发严重不受控制的并发感染或其他严重不受控制的伴随疾病，中度或重度肾损伤；
16.活动性肺部疾病，如间质性肺炎、肺炎、阻塞性肺病、哮喘，或有活动性肺结核病史。
17.凝血功能异常（INR>2.0、PT>16s），具有出血倾向或正在接受溶栓或抗凝治疗，允许预防性使用小剂量阿司匹林、低分子肝素；
3个月内，出现过显著临床意义的出血症状或具有明确的出血倾向，如日咳血或咯血2.5ml及以上，发生过消化道出血，有出血危险的食管胃底静脉曲张，出血性胃溃疡或患有脉管炎等；基线期若大便潜血阳性，可复查，复查后若仍为阳性，需要进行胃镜检查，若胃镜提示重度食管胃底静脉曲张则不能入组（入组前3个月及以内接受胃镜检查排除此类情况者除外）；
18.已知存在的遗传性或获得性出血及血栓倾向，如血友病患者，凝血机能障碍，血小板减少等；
19.研究者判断可能会增加参加研究相关的风险、或者可能干扰研究结果的解释的其它重度、急性或慢性医学疾病或实验室检查异常。

Exclusion criteria：

1. Pregnant or lactating women, and women of childbearing age who have a positive pregnancy test result at baseline; 2. Diagnosed with central nervous system metastasis by CT/MR/PET-CT; 3. Previously received anti-tumor treatment such as live vaccination or radiotherapy; 4. Patients who have participated in or are participating in other drug or therapy clinical trials within 4 weeks before the first dose of study drug; 5. Patients who have undergone major surgical procedures within 4 weeks before the first dose of study drug or have not recovered from the side effects of this surgery, and have undergone radiotherapy within 2 weeks before the first dose of study drug; 6. Patients with any primary immunodeficiency disease, active autoimmune disease, or history of autoimmune disease, including but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, vitiligo, and asthma, who have completely resolved asthma in childhood and do not need any intervention in adulthood. Asthma patients requiring bronchodilators for medical intervention cannot be included; 7. Patients with a known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation, as well as those who are using hormone therapy such as immunosuppressants or steroids for immunosuppressive purposes (dose > 10mg/day prednisone or other equivalent efficacy hormones), and continue to use them within 2 weeks before enrollment; 8. Other malignancies other than biliary tract malignancies in the past 5 years, except for cured basal cell or squamous cell carcinoma of the skin, superficial bladder cancer, early prostate cancer, cervical cancer in situ, or breast cancer; 9. Patients who have received hematopoietic stimulating factors, such as granulocyte colony-stimulating factor (G-CSF), erythropoietin and other treatments within 1 week before the first dose of study drug; 10. Patients with positive test results for acquired immunodeficiency virus (HIV) antibody or Treponema pallidum antibody, and active viral hepatitis B or C; 11. Known allergy to recombinant humanized PD-L1 monoclonal antibody drugs and their components; 12. Severe cardiovascular disease within 12 months before enrollment, such as coronary heart disease with obvious clinical symptoms, congestive heart failure of NYHA≥ class II, uncontrolled arrhythmia, myocardial infarction; 13. The following conditions occurred within 6 months before the first dose: deep vein thrombosis or pulmonary embolism; 
myocardial infarction; 
Severe or unstable arrhythmia or angina; 
percutaneous coronary intervention, acute coronary syndrome, coronary artery bypass grafting; cerebrovascular accident, transient ischemic attack, cerebral embolism. 14. Subjects who have undergone any kind of gastrointestinal surgery, or are complicated by upper gastrointestinal obstruction, bleeding, abnormal digestive function or malabsorption syndrome, which may affect the absorption of the study drug; 15. Concurrent serious uncontrolled concurrent infection or other serious uncontrolled concomitant disease, moderate or severe renal injury; 16. Active pulmonary disease, such as interstitial pneumonia, pneumonia, obstructive pulmonary disease, asthma, or a history of active tuberculosis. 17. Abnormal coagulation function (INR>2.0, PT>16s), with bleeding tendency or receiving thrombolytic or anticoagulant therapy, low-dose aspirin, low molecular weight heparin is allowed prophylactically; Within 3 months, there have been significant clinically significant bleeding symptoms or clear bleeding tendency, such as coughing up blood or hemoptysis of 2.5ml or more, gastrointestinal bleeding, esophageal and gastric varices with bleeding risk, hemorrhagic gastric ulcer, or vasculitis, etc.; If the fecal occult blood is positive at baseline, it can be re-examined, and if it is still positive after re-examination, gastroscopy is required, and if gastroscopy shows severe esophageal fundic varices, it cannot be enrolled (except for those who undergo gastroscopy to rule out such situations within 3 months before enrollment); 18. Known hereditary or acquired bleeding and thrombotic tendency, such as hemophilia patients, coagulation dysfunction, thrombocytopenia, etc.; 19. Other severe, acute or chronic medical illness or laboratory abnormality that, in the judgment of the investigator, may increase the risk associated with participation in the study or may interfere with the interpretation of the study results.ults.

研究实施时间：

Study execute time：

从 From 2026-01-01 00:00:00至 To 2027-07-31 00:00:00  

征募观察对象时间：

Recruiting time：

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

干预措施：

Interventions：

组别：

HIPEC联合CRS和度伐利尤单抗治疗组

样本量：

33

Group：

HIPEC combined with CRS and durvalumab treatment group

Sample size：

干预措施：

HIPEC联合CRS和度伐利尤单抗

干预措施代码：

Intervention：

HIPEC combined with CRS and durvalumab

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 

市(区县)：

  

Country：

China 

Province：

Shanghai 

City：

 

单位(医院)：

海军军医大学第三附属医院 

单位级别：

三级甲等 

Institution
hospital：

The Third Affiliated Hospital of Naval Medical University

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

腹水病灶的客观反应率

指标类型：

次要指标

Outcome：

Objective Response Rate of Ascites Lesions

Type：

Secondary indicator

测量时间点：

“腹水ORR评估时间点为每两疗程一次，直至疾病进展或治疗结束”

测量方法：

影像学（CT/US）+ 腹水穿刺量 + 腹围/症状

Measure time point of outcome：

The evaluation time points for ascites ORR are once every two treatment cycles, until disease progre

Measure method：

Imaging (CT/US) + Ascites fluid volume (by paracentesis) + Abdominal girth/Symptoms

指标中文名：

总生存期

指标类型：

主要指标

Outcome：

Overall survival

Type：

Primary indicator

测量时间点：

从首次给药日期（first dose date）或入组日期（enrollment date）开始观察性研究

测量方法：

主要事件（event）： 受试者死亡（无论何种原因）

Measure time point of outcome：

Observational studies starting from the first dose date or enrollment date

Measure method：

Primary endpoint: Death from any cause.

指标中文名：

客观缓解率（Objective response rate，ORR）

指标类型：

次要指标

Outcome：

Objective response rate，ORR

Type：

Secondary indicator

测量时间点：

基线以及后续定期影像学监测

测量方法：

按RECIST 1.1标准评价

Measure time point of outcome：

Baseline and subsequent regular imaging monitoring

Measure method：

Evaluated according to RECIST 1.1 criteria

指标中文名：

无进展生存期（PFS）

指标类型：

次要指标

Outcome：

Progression free survival (PFS)

Type：

Secondary indicator

测量时间点：

从治疗起始至疾病进展（PD）或死亡（任何原因）的时间。

测量方法：

RECIST 1.1测量

Measure time point of outcome：

The time from the start of treatment to disease progression (PD) or death (from any cause).

Measure method：

Evaluated according to RECIST 1.1 criteria

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：

基线评估、治疗期间随访期继续记录直到研究结束或按方案规定时间点

测量方法：

常用 CTCAE（Common Terminology Criteria for Adverse Events）v5.0 进行分级：

Measure time point of outcome：

Baseline assessment and follow-up during treatment will continue to be recorded until the end of the

Measure method：

CTCAE v5.0 grading

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 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）：

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

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)：

N/A

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：

病例记录表格（CRF）

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

Case Record Form (CRF)

数据与安全监察委员会：

Data and Safety Monitoring Committee：

无/No

注册人：

Name of Registration：

  2025-12-25 15:31:16