ChiCTR2500111114 版本V1.0 版本创建时间2025/10/27 08:45:23 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：

ChiCTR2500111114 

最近更新日期：

Date of Last Refreshed on：

2025-10-27 08:45:18 

注册时间：

Date of Registration：

2025-10-27 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

依沃西单抗（AK112）联合奥沙利铂及替吉奥在局部进展期胃及胃食管交界部腺癌新辅助治疗的有效性和安全性的前瞻性、单臂、Ⅱ期研究

Public title：

AK112 combined with Oxaliplatin plus S1 as neoadjuvant therapy for locally advanced gastric and gastroesophageal junction adenocarcinoma: a single-arm, prospective, single center trial

注册题目简写：

English Acronym：

研究课题的正式科学名称：

依沃西单抗（AK112）联合奥沙利铂及替吉奥在局部进展期胃及胃食管交界处腺癌新辅助治疗的有效性和安全性的前瞻性、单臂、Ⅱ期研究

Scientific title：

AK112 combined with Oxaliplatin plus S1 as neoadjuvant therapy for locally advanced gastric and gastroesophageal junction adenocarcinoma: a single-arm, prospective, single center trial

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：

林彧夫 

研究负责人：

申锋 

Applicant：

Lin Yufu 

Study leader：

Shen Feng 

申请注册联系人电话：

Applicant telephone：

+86 158 5926 2268

研究负责人电话：

Study leader's telephone：

+86 137 6160 0063

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：

lin.yufu@zsxmhospital.com

研究负责人电子邮件：

Study leader's E-mail：

shen.feng@zsxmhospital.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：

福建省厦门市湖里区金湖路668号

研究负责人通讯地址：

福建省厦门市湖里区金湖路668号

Applicant address：

No. 668 Jinhu Road, Huli District, Xiamen City, Fujian Province

Study leader's address：

No. 668 Jinhu Road, Huli District, Xiamen City, Fujian Province

申请注册联系人邮政编码：

Applicant postcode：

361006

研究负责人邮政编码：

Study leader's postcode：

361006

申请人所在单位：

复旦大学附属中山医院厦门医院

Applicant's institution：

Xiamen Hospital Affiliated to Zhongshan Hospital, Fudan University

研究负责人所在单位：

复旦大学附属中山医院厦门医院

Affiliation of the Leader：

Xiamen Hospital Affiliated to Zhongshan Hospital, Fudan 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：

B2025-029R

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：

复旦大学附属中山医院厦门医院伦理委员会

Name of the ethic committee：

Ethics Committee of Xiamen Hospital Affiliated to Zhongshan Hospital, Fudan University

伦理委员会批准日期：

Date of approved by ethic committee：

2025-05-23 00:00:00

伦理委员会联系人：

张博恒

Contact Name of the ethic committee：

Zhang Boheng

伦理委员会联系地址：

福建省厦门市湖里区金湖路668号

Contact Address of the ethic committee：

No. 668 Jinhu Road, Huli District, Xiamen City, Fujian Province

伦理委员会联系人电话：

Contact phone of the ethic committee：

+86 158 5926 2268

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：

复旦大学附属中山医院厦门医院

Primary sponsor：

Xiamen Hospital Affiliated to Zhongshan Hospital, Fudan University

研究实施负责（组长）单位地址：

福建省厦门市湖里区金湖路668号

Primary sponsor's address：

No. 668 Jinhu Road, Huli District, Xiamen City, Fujian 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)：

福建

市(区县)：

厦门

Country：

China

Province：

Fujian

City：

Xiamen

单位(医院)：

复旦大学附属中山医院厦门医院

具体地址：

福建省厦门市湖里区金湖路668号

Institution
hospital：

Xiamen Hospital Affiliated to Zhongshan Hospital, Fudan University

Address：

No. 668 Jinhu Road, Huli District, Xiamen City, Fujian Province

经费或物资来源：

无

Source(s) of funding：

None

Target disease：

Adenocarcinoma of the stomach and gastroesophageal junction

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：

主要目的：观察依沃西单抗（AK112）联合奥沙利铂及替吉奥在局部进展期胃及胃食管结合部腺癌新辅助治疗的有效性及安全性；探索性目的：评估受试者肿瘤组织中免疫微环境变化及微生物菌群变化。  

Objectives of Study：

Primary Objective: To observe the efficacy and safety of the combination of Ivosidenib (AK112), oxaliplatin, and tegafur in the neoadjuvant treatment of locally advanced gastric and gastroesophageal junction adenocarcinoma; Exploratory Objective: To assess changes in the immune microenvironment and microbial flora in the tumor tissue of the participants.

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.在实施任何试验相关流程之前，签署书面知情同意； 2.男性或女性，年龄>=18岁； 3.组织病理学检查确诊的局部晚期胃腺癌或胃食管交界部腺癌 4.既往未接受过针对当前疾病的系统性治疗，包括手术治疗、抗肿瘤放化疗/免疫治疗等； 5.根据 RECIST v1.1 版，至少有一个可测量病灶或者可评估病灶； 6.ECOG评分0-1分； 7.预期生存时间>6个月； 8.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>=100×10^9/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>90g/L； 4)总胆红素<=1.5×正常值上限（ULN）； 5)天门冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）在<=2.5×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）； 9.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； 10.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（或末次化疗药物给药后180天）内采用年失败率低于1%的避孕措施；

Inclusion criteria

1.Before implementing any trial-related procedures, sign a written informed consent. 2. Male or female, aged ≥ 18 years old; 3. Locally advanced gastric adenocarcinoma or adenocarcinoma of the gastroesophageal junction confirmed by histopathological examination 4. Has not received any systemic treatment for the current disease in the past, including surgical treatment, anti-tumor radiotherapy and chemotherapy/immunotherapy, etc. 5. According to RECIST v1.1 version, there is at least one measurable lesion or evaluable lesion; 6.ECOG score: 0-1 point; 7. Expected survival time >6 months; 8. Sufficient organ function. The subjects need to meet the following laboratory indicators: In the absence of granulocyte colony-stimulating factor for the past 14 days, the absolute value of neutrophils (ANC) is greater than or equal to 1.5 × 10^9/L. 2) Without blood transfusion in the past 14 days, the platelet count should be greater than or equal to 100×10^9/L. 3) In the past 14 days, without blood transfusion or the use of erythropoietin, the hemoglobin level is greater than 90g/L. 4) Total bilirubin <=1.5× upper limit of normal value (ULN); 5) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) should be within or equal to 2.5×ULN 6) Serum creatinine ≤1.5×ULN and creatinine clearance rate (calculated using the Cockcroft-Gault formula) >=60 ml/min; 7) Good coagulation function, defined as an international normalized ratio (INR) or prothrombin time (PT) <=1.5 times ULN; 8) Normal thyroid function is defined as thyroid stimulating hormone (TSH) within the normal range. If the baseline TSH exceeds the normal range, subjects with total T3 (or FT3) and FT4 within the normal range can also be enrolled. 9) The myocardial enzyme spectrum is within the normal range (if the researcher comprehensively determines that it is a simple laboratory abnormality without clinical significance, enrollment is also allowed). For female subjects of childbearing age, a urine or serum pregnancy test should be conducted within 3 days prior to the first administration of the study drug (Day 1 of cycle 1), and the result should be negative. If the result of the urine pregnancy test cannot be confirmed as negative, a blood pregnancy test is required. Women of non-childbearing age are defined as those who have been menopausal for at least one year, or have undergone surgical sterilization or hysterectomy. 10. If there is a risk of conception, all subjects (regardless of gender) are required to use contraceptive measures with an annual failure rate of less than 1% throughout the treatment period until 120 days after the last administration of the study drug (or 180 days after the last administration of the chemotherapy drug).

排除标准：

1.首次给药前5年内诊断为胃癌之外的其他恶性疾病（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.筛选期影像学显示肿瘤包绕重要血管或存在明显坏死、空洞，且研究者判定进入研究会引起出血风险； 3.贲门及幽门近乎梗阻影响患者进食及胃排空，或吞食药片有障碍； 4.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； 5.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。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； 6.研究首次给药前7天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； 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）； 7.已知异体器官移植（角膜移植除外）或异体造血干细胞移植； 8.已知对本研究中使用药物过敏者; 9.具有影响替吉奥的多种因素（比如无法吞咽和肠梗阻等）者； 10.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）； 11.已知人类免疫缺陷病毒（HIV）感染史（即HIV 1/2抗体阳性）； 12.未经治疗的慢性乙肝（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下限）； 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<500 IU/ml，受试者应在整个研究化疗药物治疗期间接受抗HBV治疗避免病毒再激活 2)对于抗HBc（+）、HBsAg（-）、抗HBs（-）和HBV病毒载量（-）的受试者，需要接受预防性抗HBV治疗 13.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）； 14.首次给药之前（第 1 周期，第 1 天）30 天内接种过活疫苗； 注：允许首次给药前 30 天内接受针对季节性流感的注射用灭活病毒疫苗；但是不允许接受鼻内用药的减毒活流感疫苗 15.妊娠或哺乳期妇女； 16.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)血压控制不理想（收缩压＞150 mmHg，舒张压＞100 mmHg）； 5)首次给药前1年内存在需要糖皮质激素治疗的非感染性肺炎病史，或当前存在临床活动性间质性肺病； 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)尿常规提示尿蛋白>=++，且证实24小时尿蛋白定量＞1.0 g者； 11)存在精神障碍且无法配合治疗的患者； 17.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 a malignant disease other than stomach cancer within 5 years prior to first administration (excluding cured basal cell carcinoma, squamous epithelial carcinoma of the skin, and / or cured in situ cancer); 2. Imaging during screening showed that the tumor surrounded important blood vessels or had a significant necrosis or void, and the researchers determined that admission to the study caused a risk of bleeding; 3. A near obstruction of the ventricles and hesophagus affects the patient's eating and emptying of the stomach, or has an impairment in swallowing pills; 4. Systemic systemic treatment with Traditional Chinese Medicine Patent Prescription or immunoregulatory drugs (including thymosin, interferon, interleukin, except for local use to control pleural effusion) within 2 weeks prior to the first administration; 5. Active autoimmune disease requiring systemic treatment (such as the use of disease-relieving drugs, corticosteroids, or immunosuppressants) occurred within 2 years prior to the initial administration. Replacement therapies (such as thyroid hormones, insulins, or physiologic glucocorticoids for adrenal gland or pituitary insufficiency) are not considered systemic; 6. They were receiving systemic corticosteroid therapy (excluding nasal, inhaled or otherwise topical corticosteroids) or any other form of immunosuppressive therapy within 7 days prior to the study's initial administration; Note: Physiological doses of glucocorticoids (<= 10 mg / day of prednisone or equivalent) are permitted; 7. It is known that heterologous organ transplants (except for corneal transplants) or heterologous hematopoietic stem cell transplants are performed; 8. Persons known to be allergic to the drug used in this study; 9. People with a variety of factors that affect thiago (such as inability to swallow and bowel obstruction); 10.Have not fully recovered from the toxicity and / or complications caused by any intervention before starting treatment (i.e., ≤ grade 1 or reached baseline, excluding fatigue or hair loss); 11. Known history of human immunodeficiency virus (HIV) infection (i.e. HIV1 / 2 antibody positive); 12. Untreated chronic hepatitis B (defined as positive HBsAg and detection of HBV-DNA copies greater than the lower limit of the laboratory normal at the research center); Note: Hepatitis B subjects who meet the following criteria are also eligible for inclusion: 1) With HBV viral load < 500 IU / ml before first administration, subjects should receive anti-HBV therapy throughout the study to avoid viral reactivation 2) For subjects with anti-HBc (+), HBsAg (-), anti-HBs (-), and HBV viral load (-), preventive anti-HBV therapy is required 13. Subjects with active HCV infection (HCV antibody positive and HCV-RNA levels above the lower detection limit); 14. Vaccinated live within 30 days prior to the first dose (cycle 1, day 1); Note: Immunization of the inactivated virus vaccine against seasonal influenza is permitted within 30 days prior to the first dose; But you're not allowed to receive a poison-reducing live influenza vaccine that's administered in the nose. 15. Women who are pregnant or breastfeeding; 16. The presence of any systemic disease that is severe or uncontrollable, such as: 1) Significant and uncontrollable abnormalities in rhythm, conduction or morphology on resting electrocardiogram, such as complete left bundle branch block, second degree or above heart block, ventricular arrhythmias or atrial fibrillation; 2) unstable angina pectoris, congestive heart failure, chronic heart failure with NYHA grade ≥ 2; 3) Any arterial thrombosis, embolism or ischemia, such as myocardial infarction, unstable angina pectoris, cerebrovascular accident or transient ischemic attack, occurred within 6 months before the treatment; 4) Poor blood pressure control (systolic > 150 mmHg, diastolic > 100 mmHg); 5) A history of non-infectious pneumonia requiring corticosteroid therapy within 1 year prior to the first dose administration, or present clinical active interstitial lung disease; 6. Active pulmonary tuberculosis; 7) The presence of an active or uncontrolled infection requiring systemic treatment; 8) There is clinical active diverticulitis, abdominal abscesses, gastrointestinal obstruction; 9) Liver disorders such as cirrhosis of liver, decompensated liver disease, acute or chronic active hepatitis; 10) The urine routine showed that the urinary protein >= + +, and confirmed that the 24-hour urinary protein quantity was > 1.0 g; 11) Patients who have a mental disorder and are unable to cooperate with treatment; 17. There may be medical history or disease evidence that interferes with trial results, prevents participants from participating throughout the study, abnormal values of treatment or laboratory tests, or other circumstances that the investigator considers unsuitable for inclusion. The investigator considered that there were other potential risks that were unsuitable for participating in this study.

研究实施时间：

Study execute time：

从 From 2025-08-01 00:00:00至 To 2027-08-01 00:00:00  

征募观察对象时间：

Recruiting time：

从From 2025-10-30 00:00:00 至 To 2026-10-30 00:00:00  

干预措施：

Interventions：

组别：

试验组

样本量：

26

Group：

Experimental Group

Sample size：

干预措施：

依沃西单抗单抗: 20mg/kg, i.v., d1, q3w; 化疗方案： 奥沙利铂130mg/m^2 i.v., d1,q3w； 替吉奥： 体表面积>1.5m^2,替吉奥剂量为60mg bid d1-14，q3w； 体表面积<1.25m^2,替吉奥剂量为40mg bid d1-14，q3w； 体表面积1.25m^2-1.5m^2,替吉奥剂量为50mg bid d1-14，q3w；

干预措施代码：

Intervention：

Ivoximab monoclonal antibody: 20 mg / kg, i.v., d1, q3w; Chemotherapy regimen: Oxaliplatin 130 mg / m^2 i.v., d1, q3w; Tessio: The body surface area was more than 1.5 m^2, and the dose of TEG was 60 mg bid d 1-14, q3w; The body surface area was less than 1.25 m^2, and the dose of TEG was 40mg bid d 1-14, q3w; The body surface area was 1.25 m^2 -1.5m^2, and the dose of TEG was 50mg bid d-1-14, q3w;

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 福建 

市(区县)：

 厦门 

Country：

China 

Province：

Fujian 

City：

Xiamen 

单位(医院)：

复旦大学附属中山医院厦门医院 

单位级别：

三甲 

Institution
hospital：

Xiamen Hospital Affiliated to Zhongshan Hospital, Fudan University

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

病理下肿瘤完全退缩率

指标类型：

主要指标

Outcome：

Pathologic Complete Remission

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

主要病理缓解

指标类型：

次要指标

Outcome：

Major Pathological Response

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

降期

指标类型：

次要指标

Outcome：

Downstaging

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

R0切除率

指标类型：

次要指标

Outcome：

Rate of R0 resection

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：

副作用指标

Outcome：

Safety

Type：

Adverse events

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

无疾病生存期

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：

主要指标

Outcome：

Overall Survival

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：

手术切除肿瘤组织

组织：

胃及胃食管交界处腺癌

Sample Name：

Surgery to remove tumor tissue

Tissue：

Adenocarcinoma of the stomach and gastroesophageal junction

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 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：

无

Blinding：

None

试验完成后的统计结果（上传文件）：

Calculated Results after
the Study Completed(upload file)：

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)：

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：

  2025-10-27 08:45:18