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：	ChiCTR2400088619
最近更新日期： Date of Last Refreshed on：	2024-08-22 11:59:22
注册时间： Date of Registration：	2024-08-22 00:00:00
注册号状态：	补注册
Registration Status：	Retrospective registration
注册题目：	HIPEC联合卡度尼利单抗和SOX化疗用于腹腔转移晚期胃癌患者转化治疗的II期临床研究
Public title：	A Phase II Clinical Study of HIPEC Combined with Cadonilimab and SOX Chemotherapy for Conversion Therapy in Patients with Advanced Gastric Cancer with Peritoneal Metastasis
注册题目简写：
English Acronym：
研究课题的正式科学名称：	HIPEC联合卡度尼利单抗和SOX化疗用于腹腔转移晚期胃癌患者转化治疗的II期临床研究
Scientific title：	A Phase II Clinical Study of HIPEC Combined with Cadonilimab and SOX Chemotherapy for Conversion Therapy in Patients with Advanced Gastric Cancer with Peritoneal Metastasis
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：	杜义安	研究负责人：	杜义安
Applicant：	Yian Du	Study leader：	Yian Du
申请注册联系人电话： Applicant telephone：	+86 138 6742 3423	研究负责人电话： Study leader's telephone：	+86 138 6742 3423
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：	duyajim@126.com	研究负责人电子邮件： Study leader's E-mail：	duyajim@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：	浙江省杭州市拱墅区半山东路1号	研究负责人通讯地址：	浙江省杭州市拱墅区半山东路1号
Applicant address：	1East Banshan Road.Gongshu District,Hangzhou,Zhejiang Province	Study leader's address：	1East Banshan Road.Gongshu District,Hangzhou,Zhejiang 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：	浙江省肿瘤医院
Applicant's institution：	Zhejiang Cancer Hospital
研究负责人所在单位：	浙江省肿瘤医院
Affiliation of the Leader：	Zhejiang Cancer 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：	IRB-2023-883(IIT)	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：	浙江省肿瘤医院医学伦理委员会
Name of the ethic committee：	Medical Ethics Committee of Zhejiang Cancer Hospital
伦理委员会批准日期： Date of approved by ethic committee：	2023-10-24 00:00:00
伦理委员会联系人：	朱骥
Contact Name of the ethic committee：	Ji Zhu
伦理委员会联系地址：	浙江省杭州市拱墅区半山东路1号
Contact Address of the ethic committee：	1East Banshan Road.Gongshu District,Hangzhou,Zhejiang Province
伦理委员会联系人电话： Contact phone of the ethic committee：	+86 571 8812 2564	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：

浙江省肿瘤医院

Primary sponsor：

Zhejiang Cancer Hospital

研究实施负责（组长）单位地址：

浙江省杭州市拱墅区半山东路1号

Primary sponsor's address：

1East Banshan Road.Gongshu District,Hangzhou,Zhejiang 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)：	浙江	市(区县)：
Country：	China	Province：	Zhejiang Province	City：
单位(医院)：	浙江省肿瘤医院	具体地址：	浙江省杭州市拱墅区半山东路1号
Institution hospital：	Zhejiang Cancer Hospital	Address：	1East Banshan Road.Gongshu District,Hangzhou,Zhejiang Province

经费或物资来源：

公司资助

Source(s) of funding：

Company funding

研究疾病：

胃癌

Target disease：

gastric cance

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：

其它

Study phase：

N/A

研究设计：

单臂

Study design：

Single arm

研究目的：

主要目的 ·评价HIPEC联合卡度尼利单抗和SOX化疗用于腹腔转移晚期胃癌患者的R0手术转化率。次要目的 · 评价HIPEC联合卡度尼利单抗和SOX化疗用于腹腔转移晚期胃癌患者的R0切除率。 • 评价HIPEC联合卡度尼利单抗和SOX化疗用于腹腔转移晚期胃癌患者的客观缓解率（Objective response rate，ORR）、无进展生存期（progression-free survival，PFS）、总生存期（Overall survival，OS）、腹膜癌指数缓解率（peritoneal cancer index，PCI）。 · 评价HIPEC联合卡度尼利单抗和SOX化疗用于腹腔转移晚期胃癌患者的安全性（Safety)。探索性目的 · 探索性分析受试者血液标本中的免疫细胞水平（外周血淋巴细胞免疫分型及淋巴细胞亚群计数）与疗效的相关性。 · 评估受试者肿瘤组织中PD-L1 CPS表达水平及TMB水平与疗效的相关性。

Objectives of Study：

Primary Objective: - Evaluate the R0 surgical conversion rate of HIPEC combined with Cadonilimab and SOX chemotherapy in patients with advanced gastric cancer with peritoneal metastasis. Secondary Objectives: - Evaluate the R0 resection rate of HIPEC combined with Cadonilimab and SOX chemotherapy in patients with advanced gastric cancer with peritoneal metastasis. - Evaluate the objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and peritoneal cancer index (PCI) of HIPEC combined with Cadonilimab and SOX chemotherapy in patients with advanced gastric cancer with peritoneal metastasis. - Assess the safety of HIPEC combined with Cadonilimab and SOX chemotherapy in patients with advanced gastric cancer with peritoneal metastasis. Exploratory Objectives: - Explore the correlation between levels of immune cells (peripheral blood lymphocyte immunotyping and lymphocyte subset counting) in subjects' blood specimens and efficacy. - Evaluate the correlation between PD-L1 CPS expression levels and TMB levels in subjects' tumor tissues and efficacy.

药物成份或治疗方案详述：

Description for medicine or protocol of treatment in detail：

纳入标准：

患者必须满足以下所有标准才可进入本研究：
1)	自愿签署书面知情同意书。
2)	年龄≥18周岁且≤75周岁，男女均可。
3)	ECOG体能状况评分0或1。
4)	经组织学/细胞学确诊的晚期胃（或胃食管结合部）腺癌；
5)	经腹腔镜探查及拍照确诊存在胃癌腹腔转移（CT或MRI确证无其它转移部位），且PCI≤ 20
6)	既往未接受过抗肿瘤治疗（针对胃或胃食管结合部的手术，放疗，化疗，免疫治疗等）；
7)	预期生存期>3个月；
8)	根据RECIST v1.1，受试者必须至少有一个可测量的病灶。
9)	通过以下要求确定良好的器官功能：
a. 血液学（受试者首次给药前7天内受试者不允许接受输血或生长因子支持治疗）：
i.中性粒细胞绝对计数（ANC）≥1.5×109/L（1500/mm3）；
ii.血小板计数≥100×109/L（100000/mm3）；
iii.血红蛋白≥90g/L。
b. 肾脏：
i.肌酐清除率* (CrCl) 计算值 ≥ 50 mL/min或者血清肌酐≤1.5×ULN
* 将采用 Cockcroft-Gault 公式计算 CrCl 
CrCL (mL/min) = {(140-年龄)×体重 (kg)×F}/(SCr(mg/dL)×72)
其中男性的F=1，女性的F=0.85；SCr=血清肌酐。
ii.尿蛋白< 2+或24小时（h）尿蛋白定量 <1.0 g。
c. 肝脏：
i.血清总胆红素（TBiL)≤1.5×ULN；
ii.AST和ALT≤2.5×ULN；
iii.血清白蛋白（ALB）≥28 g/L。
d. 凝血功能：国际标准化比值（INR）和活化部分凝血活酶时间（APTT）≤1.5×ULN（除非受试者正在接受抗凝剂治疗，并且INR和APTT处在使用抗凝剂治疗的预期范围内）。
e. 心功能：左室射血分数（LVEF）≥ 50%。
10)	无与本方案相冲突的其他严重疾病（如自身免疫性疾病、免疫缺陷、器官移植或其他需要持续激素治疗的疾病）；
11)	具有生育能力的女性受试者必须在首次给药前3天内进行尿液或血清妊娠检查（如尿液妊娠检查结果不能确认为阴性，需进行血清妊娠检查，以血清妊娠结果为准），且结果为阴性。如具有生育能力的女性受试者与未绝育的男性伴侣发生性行为，该受试者必须自筛选开始采取高效的避孕方法，且必须同意在研究治疗期间和研究治疗期结束后180天内采用有效方法避孕。关于在此时间点后是否停止避孕，应与研究者讨论。
12)	如未绝育的男性受试者与具有生育能力的女性伴侣发生性行为，该受试者必须自筛选开始至末次给药后的第80天采取有效的避孕方法；关于在此时间点后是否停止避孕，应与研究者讨论。
13)	受试者愿意而且能够遵守日程表规定的访视、治疗方案、实验室检查，及遵守研究的其他要求

Inclusion criteria

Patients must meet all of the following criteria to enter this study:
1) Voluntarily sign a written informed consent form.
2) Age ≥18 and ≤75 years, both males and females are eligible.
3) ECOG performance status of 0 or 1.
4) Histologically/cytologically confirmed advanced gastric (or gastroesophageal junction) adenocarcinoma.
5) Presence of peritoneal metastasis from gastric cancer confirmed by laparoscopic exploration and photography (CT or MRI confirms no metastasis outside the peritoneum), with PCI ≤ 20.
6) No prior anticancer therapy (including surgery, radiotherapy, chemotherapy, immunotherapy, etc.) for gastric or gastroesophageal junction.
7) Expected survival period >3 months.
8) At least one measurable lesion according to RECIST v1.1.
9) Good organ function determined by the following requirements:
   a. Hematology (subjects are not allowed to receive blood transfusions or growth factor support therapy within 7 days before the first dose):
      i. Absolute neutrophil count (ANC) ≥1.5×109/L (1500/mm3);
      ii. Platelet count ≥100×109/L (100000/mm3);
      iii. Hemoglobin ≥90 g/L.
   b. Renal function:
      i. Calculated creatinine clearance rate (CrCl) ≥ 50 mL/min or serum creatinine ≤1.5×ULN
      CrCL (mL/min) = {(140-age)×weight (kg)×F}/(SCr(mg/dL)×72)

F: 0.85 (for females) or 1 (for males)
   c. Liver function:
      i. Total bilirubin (TBIL) ≤1.5×ULN;
      ii. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN (≤5×ULN if liver metastasis is present).
iii.Serum albumin (ALB) ≥28 g/L.
d. Coagulation function: International Normalized Ratio (INR) and activated partial thromboplastin time (APTT) ≤1.5×ULN (unless the subject is receiving anticoagulant therapy and INR and APTT are within the expected range of anticoagulant therapy).
e. Cardiac function: Left ventricular ejection fraction (LVEF) ≥ 50%.
10) no other serious medical conditions that conflict with this protocol (such as autoimmune diseases, immune deficiencies, organ transplants, or other conditions requiring continuous hormone therapy);
11) Fertile female subjects must undergo a urine or serum pregnancy test within 3 days before the first dose (if the urine pregnancy test results cannot be confirmed as negative, a serum pregnancy test is required, based on the serum pregnancy result), and the result is negative. If a fertile female subject has sex with an unsterilized male partner, the subject must use a highly effective method of contraception since screening and must consent to use an effective method of contraception during the study treatment period and for 180 days after the end of the study treatment period. Whether to stop contraception after this time point should be discussed with the investigator.
12) If an unsterilized male subject has sex with a fertile female partner, the subject must use an effective contraceptive method from the beginning of screening until the 80th day after the last dose; Whether to stop contraception after this time point should be discussed with the investigator.
13) The subject is willing and able to comply with scheduled visits, treatment protocols, laboratory tests, and other requirements of the study

排除标准：

具有以下任意一项的患者不得进入本研究： 1) 患者既往接受过抗肿瘤治疗（包括化疗，放疗，手术或免疫治疗等）。 2) 已知的HER-2阳性患者。 3) 经影像学确证存在腹腔转移以外的远处转移患者(包括肝转移，腹主动脉旁淋巴结转移，肺转移等)； 4) 既往存在胃部手术史； 5) 存在无法吞咽、慢性腹泻和肠梗阻等影响口服药物服用吸收的多种因素； 6) 签署知情同意书前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；基线期需要进行胃镜检查，若胃镜结果提示有重度胃溃疡或研究者判断有出血风险则不能入组（签署知情同意书前3个月及以内接受胃镜检查排除此类情况且基线期便潜血阴性者除外）；签署知情同意前6个月内出现过胃肠道穿孔或胃肠道瘘； 7) 既往患其他恶性肿瘤的受试者，除非进入研究前至少5年已达到完全消除，且研究期间不需要或预计不需要接受额外治疗（例外情况包括但不限于，基底或鳞状细胞皮肤癌、浅表膀胱癌或前列腺、宫颈或乳腺原位癌）； 8) 患有已知或可疑的活动性自身免疫性疾病的受试者。允许纳入患I型糖尿病、仅需要进行激素替代治疗的甲状腺功能减退、不需要全身性治疗的皮肤疾病（如，白癜风、银屑病或脱发）或在无外部触发因素的情况下，预计不会复发的病症的受试者； 9) 既往存在心肌炎、心肌病、恶性心律失常病史。首次给药前12个月内存在需住院治疗的不稳定性心绞痛、心肌梗塞、充血性心力衰竭（按照纽约心脏病协会功能分级确定的2级及以上）或血管疾病（如存在破裂风险的主动脉瘤），或可能影响研究药物安全性评价的其他心脏损害（如控制不佳的心律失常，心肌缺血）。 10) 首次给药前6个月内发生过任何动脉血栓栓塞事件，NCI CTCAE 5.0版3级及以上的静脉血栓栓塞事件，短暂性脑缺血发作，脑血管意外，高血压危象或高血压脑病；首次给药前1个月内发生慢性阻塞性肺病急性加重；当前存在高血压且经口服降压药物治疗后收缩压≥160 mmHg或舒张压≥100 mmHg。 11) 给予研究药物前14天内患需要皮质类固醇（＞10mg每日强的松或等效剂量）或其他免疫抑制药物全身性治疗的病症的受试者。在没有活动性自身免疫性疾病的情况下，使用＞10mg每日强的松等效剂量的吸入性或外用类固醇和肾上腺替代性类固醇； 12) 既往或当前存在需要系统性糖皮质激素治疗的非感染性肺炎/间质性肺疾病（包括放射性肺炎）。 13) 既往接受过抗PD-1、抗PD-L1、抗PD-L2、抗CD137或抗CTLA-4抗体或任何其他抗体或以T细胞共刺激或检查点通路为特异性靶点的药物的治疗； 14) 根据研究者的意见，可能增加研究参与、研究药物给药相关风险或可损害受试者接受试验方案治疗的能力的任何严重或未得到控制的医学疾病或活动性感染； 15) 活动性或既往有明确的炎症性肠病（如克罗恩病、溃疡性结肠炎或慢性腹泻）病史。 16) 首次给药前4周内发生严重感染，包括但不局限于伴有需要住院治疗的合并症、败血症或严重肺炎；在首次给药前2周内接受过全身抗感染治疗的活动性感染（不包括乙型肝炎或丙型肝炎的抗病毒治疗）。 17) 已知存在活动性肺结核（TB），怀疑有活动性TB的受试者，需进行临床检查排除；已知的活动性梅毒感染。 18) 当前存在活动性乙型肝炎的受试者（HBsAg阳性且HBV-DNA超过1000拷贝/ml（200 IU/ml）或高于检测下限，以高者为准），对于患有乙型肝炎的受试者，要求在研究治疗期间接受抗乙肝病毒治疗；活动性的丙型肝炎受试者（HCV抗体阳性且HCV-RNA水平高于检测下限）。 19) 已知有人免疫缺陷病毒（HIV）检测阳性史或已知患获得性免疫缺陷综合征（AIDS）； 20) 已知异体器官移植史和异体造血干细胞移植史。 21) 在接受首次治疗后30天内接种了活疫苗/减毒疫苗的受试者； 22) 对研究药物成分过敏或超敏病史，对任何单克隆抗体有重度超敏反应病史； 23) 已知有精神疾病、药物滥用、酗酒或吸毒史。 24) 妊娠或哺乳期女性。 25) 其他研究者评价不符合入组条件者。

Exclusion criteria：

tients with any of the following were not admitted to the study: 1) Patients have previously received anti-tumor therapy (including chemotherapy, radiotherapy, surgery, or immunotherapy). 2) Known HER-2 positive patients. 3) Patients with distant metastases other than abdominal metastasis confirmed by imaging (including liver metastasis, para-aortic lymph node metastasis, lung metastasis, etc.); 4) Previous history of gastric surgery; 5) There are many factors affecting the absorption of oral drugs such as inability to swallow, chronic diarrhea and intestinal obstruction; 6) Within 3 months before signing the informed consent, there have been clinically significant bleeding symptoms or definite bleeding tendency, such as gastrointestinal bleeding, esophageal and gastric varices with bleeding risk, hemorrhagic ulcer or vasculitis; At baseline, gastroscopy is required, and if the gastroscopy results indicate severe gastric ulcer or the researchers judge that there is a risk of bleeding, they cannot be enrolled in the group (except those who receive gastroscopy within 3 months before signing the informed consent to rule out such conditions and have negative occipal blood at baseline); Gastrointestinal perforation or fistula within 6 months prior to signing the informed consent; 7) Subjects with previous malignancies, unless complete elimination has been achieved at least 5 years prior to study entry, and additional treatment is not or is not expected to be required during the study period (exceptions include, but are not limited to, basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast); 8) Subjects with a known or suspected active autoimmune disease. Allow inclusion of subjects with type I diabetes, hypothyroidism requiring hormone replacement therapy only, skin conditions that do not require systemic treatment (e.g., vitiligo, psoriasis, or hair loss), or conditions that are not expected to recur in the absence of external triggers; 9) History of myocarditis, cardiomyopathy, and malignant arrhythmia. Unstable angina, myocardial infarction, congestive heart failure (grade 2 or higher as defined by the New York Heart Association Functional Scale), or vascular disease (such as aortic aneurysms at risk of rupture), or other heart damage (such as poorly controlled arrhythmias, myocardial ischemia) that may affect the safety evaluation of the study drug in the 12 months prior to initial administration. 10) Any arterial thromboembolism event, NCI CTCAE 5.0 grade 3 or above venous thromboembolism event, transient ischemic attack, cerebrovascular accident, hypertensive crisis, or hypertensive encephalopathy occurred within 6 months prior to initial administration; Acute exacerbation of chronic obstructive pulmonary disease occurred within 1 month before first administration; Current hypertension with systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg after oral antihypertensive medication. 11) Subjects with conditions requiring systemic treatment with corticosteroids (> 10mg daily prednisone or equivalent dose) or other immunosuppressive drugs within 14 days prior to administration of the study drug. In the absence of active autoimmune disease, use > 10mg of daily prednisone equivalent doses of inhaled or topical steroids and adrenal substitute steroids; 12) The presence of past or current non-infectious pneumonia/interstitial lung disease (including radiation pneumonia) that requires systemic glucocorticoid therapy. 13) Prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137 or anti-CTLA-4 antibodies or any other antibodies or drugs that specifically target T cell co-stimulation or checkpoint pathways; 14) any serious or uncontrolled medical condition or active infection that, in the opinion of the investigator, may increase study participation, risks associated with study drug administration, or impair the ability of the subject to receive treatment under the experimental protocol; 15) Active or prior history of a clear inflammatory bowel disease (such as Crohn's disease, ulcerative colitis, or chronic diarrhea). 16) Severe infection within 4 weeks prior to initial dosing, including but not limited to comorbidities requiring hospitalization, sepsis, or severe pneumonia; Active infections that have received systemic anti-infective therapy within 2 weeks prior to initial dosing (excluding antiviral therapy for hepatitis B or C). 17) Subjects with known active tuberculosis (TB) and suspected active TB should be ruled out by clinical examination; Known active syphilis infection. 18) Subjects with current active hepatitis B (HBsAg positive with more than 1000 copies /ml (200 IU/ml) of HBV-DNA or higher than the lower limit of detection, whichever is higher), and subjects with hepatitis B are required to receive anti-hepatitis B therapy during the study treatment; Active hepatitis C subjects (HCV antibody positive with HCV-RNA levels above the lower limit of detection). 19) Known human immunodeficiency virus (HIV) testing history or known to have acquired immunodeficiency syndrome (AIDS); 20) Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation. 21) Subjects who received the live/attenuated vaccine within 30 days of receiving the first treatment; 22) A history of allergy or hypersensitivity to the investigational drug ingredient and a history of severe hypersensitivity to any monoclonal antibody; 23) A known history of mental illness, substance abuse, alcohol or drug abuse. 24) Pregnant or lactating women. 25) Those who did not meet the eligibility criteria assessed by other researchers.

研究实施时间：

Study execute time：

从 From 2024-01-24 00:00:00至 To 2025-12-31 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2024-04-18 00:00:00 至 To 2025-06-30 00:00:00

干预措施：

Interventions：

组别：	针对经组织学/细胞学确诊的胃（或胃食管结合部）腺癌患者，经腹腔镜探查或腹腔灌洗液评价确诊存在胃癌腹腔转移，且影像学确证无其它部位的远处转移，腹膜癌指数（PCI）≤ 20，排除已知的HER-2阳性患者。	样本量：	46
Group：	The study targets patients with histologically/cytologically confirmed gastric (or gastroesophageal junction) adenocarcinoma, diagnosed with gastric cancer peritoneal metastasis through laparoscopic exploration or peritoneal lavage cytology, and confirmed by imaging to have no distant metastasis at other sites, with peritoneal cancer index (PCI) ≤ 20, excluding known HER-2 positive patients.	Sample size：	46
干预措施：	转化治疗阶段: 受试者接受HIPEC（腹腔热灌注化疗）：紫杉醇 75mg/m2,d1,3，在腹腔探查术结束后72小时内完成，紫杉醇腹腔热灌注化疗前半小时行预处理；卡度尼利单抗10mg/kg，每个周期第1天静脉滴注给药；待患者进食后（一般在术后48小时内）予S-1口服，80-120 mg,（<1.25 m2, 40 mg; 1.25 to ≤1.5 m2, 50 mg; and ≥ 1.5 m2, 60 mg），分2次，口服14天；每3周为1个疗程，治疗持续1个周期。卡度尼利单抗10mg/kg，每个周期第1天静脉滴注给药：奥沙利铂在第一个周期的第1天以130 mg/m2的剂量静脉输注；在第1天至第14天每天两次口服替吉奥80-120mg；每3周为1个疗程，治疗持续4个周期。以上治疗方案转化治疗阶段每6周（±7天）进行一次影像学检查，完成4个周期治疗后进行MDT综合评估，判断能否进行根治性手术。探查PCI评分小于6分，且原发灶可根治性切除。患者则行原发灶D2/D+术联合腹腔肿瘤细胞减灭术（CRS），术后继续进行4个周期辅助治疗，辅助结束后（卡度尼利+替吉奥）后续维持治疗一年。随后进入随访期。对于不能手术的患者，如果疾病稳定，未出现疾病进展，则继续原方案进行4个周期治疗，后续患者将继续卡度尼利单抗加替吉奥维持治疗一年。不可手术且疾病进展的患者直接出组，按照临床诊疗规范给予二线治疗；具体治疗方案如下：手术治疗后的辅助治疗： HIPEC（腹腔热灌注化疗）：紫杉醇 75mg/m2,d1,3，术后72小时内完成，紫杉醇腹腔热灌注化疗前半小时行预处理；术后4-6周继续治疗，卡度尼利单抗10mg/kg，每个周期第1天静脉滴注给药；奥沙利铂在第一个周期的第1天以130 mg/m2的剂量静脉输注；在第1天至第14天每天两次口服替吉奥80-120mg；每3周为1个治疗周期，治疗持续4个周期；无法手术治疗但疾病未进展患者的后续治疗： HIPEC（腹腔热灌注化疗）：紫杉醇 75mg/m2,d1,3，在腹腔探查术结束后72小时内完成，紫杉醇腹腔热灌注化疗前半小时行预处理；卡度尼利单抗10mg/kg，每个周期第1天静脉滴注给药；待患者进食后（一般在术后48小时内）予S-1口服，80-120 mg,（<1.25 m2, 40 mg; 1.25 to ≤1.5 m2, 50 mg; and ≥ 1.5 m2, 60 mg），分2次，口服14天；每3周为1个疗程，治疗持续1个周期。随后卡度尼利单抗10mg/kg，每个周期第1天静脉滴注给药；奥沙利铂在第一个周期的第1天以130 mg/m2的剂量静脉输注；在第1天至第14天每天两次口服替吉奥80-120mg；每3周为1个疗程，治疗持续4个周期，后续患者将继续卡度尼利单抗加替吉奥维持治疗一年。	干预措施代码：
Intervention：	Subjects will receive HIPEC (hyperthermic intraperitoneal chemotherapy): paclitaxel 75mg/m2, d1,3, completed within 72 hours after laparoscopic exploration, with pre-treatment with paclitaxel half an hour before HIPEC; Cadonilimab 10mg/kg, administered by intravenous infusion on day 1 of each cycle; S-1 oral administration after patient's meal (generally within 48 hours after surgery), 80-120 mg (<1.25 m2, 40 mg; 1.25 to ≤1.5 m2, 50 mg; and ≥ 1.5 m2, 60 mg), divided into two doses, oral administration for 14 days; one cycle every 3 weeks, treatment lasts for one cycle. Cadonilimab 10mg/kg, administered by intravenous infusion on day 1 of each cycle; oxaliplatin administered on day 1 of the first cycle at a dose of 130 mg/m2 by intravenous infusion; oral administration of tegafur 80-120mg twice daily from day 1 to day 14; one cycle every 3 weeks, treatment lasts for 4 cycles. During the conversion therapy phase, imaging examinations will be conducted every 6 weeks (±7 days). After completing 4 cycles of treatment, a multidisciplinary team (MDT) comprehensive evaluation will be performed to determine whether radical surgery can be performed. If the PCI score is less than 6 and the primary lesion is resectable, patients will undergo D2/D+ surgery combined with cytoreduction of peritoneal tumor cells (CRS). After surgery, 4 cycles of adjuvant therapy will be continued, followed by maintenance therapy (Cadonilimab + tegafur) for one year. Subsequently, patients will enter the follow-up period. For patients who cannot undergo surgery, if the disease is stable and there is no disease progression, 4 cycles of treatment will be continued according to the original protocol. Patients will continue to receive Cadonilimab plus tegafur maintenance therapy for one year. Patients who are ineligible for surgery and have disease progression will be directly discontinued from the study and will be given second-line treatment according to clinical diagnosis and treatment guidelines. The specific treatment plan is as follows: Adjuvant therapy after surgical treatment: HIPEC (hyperthermic intraperitoneal chemotherapy): paclitaxel 75mg/m2, d1,3, completed within 72 hours after surgery, with pre-treatment with paclitaxel half an hour before HIPEC; continue treatment 4-6 weeks after surgery, Cadonilimab 10mg/kg, administered by intravenous infusion on day 1 of each cycle; oxaliplatin administered on day 1 of the first cycle at a dose of 130 mg/m2 by intravenous infusion; oral administration of tegafur 80-120mg twice daily from day 1 to day 14; one cycle every 3 weeks, treatment lasts for 4 cycles; Follow-up treatment for patients who cannot undergo surgical treatment but have no disease progression: HIPEC (hyperthermic intraperitoneal chemotherapy): paclitaxel 75mg/m2, d1,3, completed within 72 hours after laparoscopic exploration, with pre-treatment with paclitaxel half an hour before HIPEC; Cadonilimab 10mg/kg, administered by intravenous infusion on day 1 of each cycle; S-1 oral administration after patient's meal (generally within 48 hours after surgery), 80-120 mg (<1.25 m2, 40 mg; 1.25 to ≤1.5 m2, 50 mg; and ≥ 1.5 m2, 60 mg), divided into two doses, oral administration for 14 days; one cycle every 3 weeks, treatment lasts for one cycle. Subsequently, Cadonilimab 10mg/kg, administered by intravenous infusion on day 1 of each cycle; oxaliplatin administered on day 1 of the first cycle at a dose of 130 mg/m2 by intravenous infusion; oral administration of tegafur 80-120mg twice daily from day 1 to day 14; one cycle every 3 weeks, treatment lasts for 4 cycles, followed by Cadonilimab plus tegafur maintenance therapy for one year. All enrolled subjects will receive continuous treatment until the investigator determines no clinical benefit (based on RECIST v1.1 imaging assessment and comprehensive evaluation of clinical status), intolerable toxicity, initiation of new anti-tumor treatment, completion of protocol-defined treatment, or meeting other criteria for treatment termination in the protocol, whichever occurs first.	Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：	中国	省(直辖市)：	浙江省	市(区县)：
Country：	China	Province：	Zhejiang Province	City：
单位(医院)：	浙江省肿瘤医院	单位级别：	三甲
Institution hospital：	Zhejiang Cancer Hospital	Level of the institution：	Tertiary A

测量指标：

Outcomes：

指标中文名：	影像检查结果	指标类型：	主要指标
Outcome：	Results of Imaging examinations	Type：	Primary 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：	Hematology	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	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:

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）：	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：	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：	暂未确定/Not yet
注册人： Name of Registration：	2024-08-22 11:59:16