ChiCTR2600121591 版本V1.0 版本创建时间2026/04/01 10:44:07 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：

 ChiCTR2600121591 

最近更新日期：

Date of Last Refreshed on：

 2026-04-01 10:44:01 

注册时间：

Date of Registration：

 2026-04-01 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

一项评价司替戊醇联合免疫化疗用于HER2阴性不可切除晚期胃癌治疗的I期剂量爬坡临床研究

Public title：

A Phase I Dose-Escalation Clinical Study Evaluating Stiripentol Combined with Immunochemotherapy for the Treatment of HER2-Negative Unresectable Advanced Gastric Cancer

注册题目简写：

English Acronym：

研究课题的正式科学名称：

一项评价司替戊醇联合免疫化疗用于HER2阴性不可切除晚期胃癌治疗的I期剂量爬坡临床研究

Scientific title：

A Phase I Dose-Escalation Clinical Study Evaluating Stiripentol Combined with Immunochemotherapy for the Treatment of HER2-Negative Unresectable Advanced Gastric Cancer

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：

赵旻奕 

研究负责人：

张常华;赵奕;陈鸿 

Applicant：

Changhua Zhang 

Study leader：

Zhang Changhua; Zhao Yi; Chen Hong 

申请注册联系人电话：

Applicant telephone：

 +86 158 7428 2815

研究负责人电话：

Study leader's
telephone：

+86 755 8120 6211

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：

 zhaomy26@mail.sysu.edu.cn

研究负责人电子邮件：

Study leader's E-mail：

 zhchangh@mail.sysu.edu.cn

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：

中国广东省深圳市光明区光明街道光桥路东侧圳园路628号

研究负责人通讯地址：

中国广东省深圳市光明区光明街道光桥路东侧圳园路628号

Applicant address：

No. 628, Zhenyuan Road, East Side of Guangqiao Road, Guangming Street, Guangming District, Shenzhen, Guangdong, China

Study leader's address：

No. 628, Zhenyuan Road, East Side of Guangqiao Road, Guangming Street, Guangming District, Shenzhen, Guangdong, 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：

中山大学附属第七医院（深圳）

Applicant's institution：

The Seventh Affiliated Hospital of Sun Yat-sen University (Shenzhen)

研究负责人所在单位：

中山大学附属第七医院(深圳)

Affiliation of the Leader：

The Seventh Affiliated Hospital of Sun Yat-sen University (Shenzhen)

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：

 KY-2025-093-01

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：

中山大学附属第七医院（深圳）科研伦理委员会

Name of the ethic committee：

Research Ethics Committee of the Seventh Affiliated Hospital of Sun Yat-sen University (Shenzhen)

伦理委员会批准日期：

Date of approved by ethic committee：

 2025-03-24 00:00:00

伦理委员会联系人：

唐燕

Contact Name of the ethic committee：

Yan Tang

伦理委员会联系地址：

中国广东省深圳市光明区光明街道光桥路东侧、圳园路628号

Contact Address of the ethic committee：

No. 628, Zhenyuan Road, East Side of Guangqiao Road, Guangming Street, Guangming District, Shenzhen, Guangdong, China

伦理委员会联系人电话：

Contact phone of the ethic committee：

 +86 755 8120 7260

伦理委员会联系人邮箱：

Contact email of the ethic committee：

 tangyan2@sysush.com

研究实施负责（组长）单位：

中山大学附属第七医院(深圳)

Primary sponsor：

The Seventh Affiliated Hospital of Sun Yat-sen University (Shenzhen)

研究实施负责（组长）单位地址：

中国广东省深圳市光明区光明街道光桥路东侧、圳园路628号

Primary sponsor's address：

No. 628, Zhenyuan Road, East Side of Guangqiao Road, Guangming Street, Guangming District, Shenzhen, Guangdong, 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)：

广东

市(区县)：

Country：

China

Province：

Guangdong

City：

单位(医院)：

中山大学附属第七医院

具体地址：

中国广东省深圳市光明区光明街道光桥路东侧、圳园路628号

Institution
hospital：

The Seventh Affiliated Hospital of Sun Yat-sen University

Address：

No. 628, Zhenyuan Road, East Side of Guangqiao Road, Guangming Street, Guangming District, Shenzhen, Guangdong, China

经费或物资来源：

中山大学5010计划

Source(s) of funding：

Sun Yat-sen University 5010 Program

研究疾病：

初治HER2阴性不可切除晚期胃癌  

Target disease：

Treatment-na?ve HER2-negative unresectable advanced gastric 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：

 I期临床试验 

Study phase：

1

研究设计：

单臂 

Study design：

Single arm 

研究目的：

明确司替戊醇联合免疫化疗治疗HER2阴性晚期胃癌的安全性，探索其最大耐受剂量。  

Objectives of Study：

To clarify the safety profile of stiripentol in combination with immunochemotherapy for the treatment of HER2-negative advanced gastric cancer, and to determine its maximum tolerated dose.

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.性别：不限; 2.年龄（在知情同意时）：18岁及以上； 3.患有不可切除的晚期胃癌（1.不可切除局部进展胃癌，肿瘤组织外侵和系膜根部组织黏连、肿瘤组织包绕大血管或转移淋巴结包绕门静脉或主动脉等大血管；2.晚期转移胃癌），经组织学确诊为腺癌，HER2阴性，且未接受过任何抗肿瘤治疗的患者； 4.在筛选入组前 28 天内，在 CT 或 MRI 图像上具有《实体瘤疗效评价标准（RECIST）1.1 版》所定义的可测量病灶。 5.能够提供肿瘤组织标本（档案或新鲜活检标本）用于PD-L1表达分析。对于无法进行其他活检的患者，档案标本可作为替代选择； 6.ECOG PS评分为0或1； 7.预期寿命至少为3个月； 8.在筛选入组前7天内具有符合以下标准的最新实验室数据。如果随机分组时的实验室检查日期不在试验药物首次给药前的7天内，则应在试验药物首次给药前 7 天内重复进行检测，并且必须确认试验药物首次给药前的最新实验室数据符合以下标准。需要注意的是，如果患者在检测前14天内接受过粒细胞集落刺激因子（G-CSF）或输血，则实验室数据将无效,1)白细胞≥3000/mm^3，中性粒细胞≥1500/mm^3 2)血小板≥80000/mm^3 3)血红蛋白≥8.0g/dL 4)天冬氨酸转氨酶（谷氨酸-草酰乙酸转氨酶）（AST[GOT]）和丙氨酸转氨酶（谷丙酸转氨酶）（ALT[GPT]）≤3.0×ULN（研究单位标准），或肝转移患者≤5.0×UL 5)总胆红素≤2.0×ULN 6)肌酐≤1.5#1×ULN或肌酐清除率（Cockcroft-Gault）>60 mL/min #1：需要注意的是，如果在第2部分中选择了SOX治疗，那么开始SOX治疗的标准是≤1.2×ULN； 9.有生育能力的妇女（包括化学绝经或因其他医疗原因没有月经的妇女）#2必须同意从知情同意开始使用避孕措施#3，直到最后一次用药或联合化疗后至少5个月，以较晚者为准。此外，妇女必须同意从知情同意之日起直到最后一剂研究产品或联合化疗后至少5个月后不得母乳喂养，以较晚者为准； 10.男性必须同意从研究治疗开始就使用避孕措施#3，直到最后一剂研究药物或联合化疗后至少7个月，以较晚者为准。 #2：有生育能力的妇女被定义为在月经开始后未绝经且未进行手术绝育的所有妇女（如子宫切除术、双侧输卵管结扎、双侧卵巢切除术）。绝经后定义为≥连续12个月闭经，无具体原因。使用口服避孕药或机械避孕药，如宫内节育器和避孕障碍的妇女被认为有生育潜力。 #3：患者必须同意使用以下不同避孕方法中的至少两种： 对于男性患者或女性患者的男性伴侣，可采用输精管切除术或使用避孕套;对于女性患者或男性患者的女性伴侣，可采用输卵管结扎术、子宫托、宫内节育器和口服避孕药。

Inclusion criteria

1.Sex: Male or female; 2.Age: 18 years or older at the time of informed consent; 3.Disease Status: Patients with unresectable advanced gastric cancer (including 1. Unresectable locally advanced gastric cancer with tumor invasion and adhesion to the root of the mesentery, tumor encasement of major vessels, or metastatic lymph nodes encasing major vessels such as the portal vein or aorta; 2. Metastatic advanced gastric cancer), histologically confirmed adenocarcinoma, HER2-negative, and who have not received any prior anti-tumor therapy; 4.Measurable Lesions: Presence of at least one measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 on CT or MRI scan performed within 28 days prior to screening enrollment; 5.Tumor Tissue: Ability to provide a tumor tissue sample (archived or from a fresh biopsy) for PD-L1 expression analysis. For patients unable to undergo a new biopsy, an archival sample is an acceptable alternative; 6.ECOG Performance Status: Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; 7.Life Expectancy: Life expectancy of at least 3 months; 8.Adequate Organ Function: Have the following latest laboratory data meeting the criteria below within 7 days prior to screening enrollment. If the laboratory test date at randomization is not within 7 days before the first dose of the study drug, the test must be repeated within 7 days before the first dose of the study drug, and the latest laboratory data before the first dose of the study drug must be confirmed to meet the following criteria. Note that laboratory data will be considered invalid if the patient has received granulocyte colony-stimulating factor (G-CSF) or blood transfusion within 14 days prior to the test. White Blood Cell (WBC) count >=3000/mm^3, Absolute Neutrophil Count (ANC) >= 1500/mm^3 Platelet count >= 80000/mm^3 Hemoglobin >= 8.0 g/dL Aspartate Aminotransferase (AST [GOT]) and Alanine Aminotransferase (ALT [GPT]) <= 3.0 × Upper Limit of Normal (ULN) (institutional standard), or <= 5.0 × ULN for patients with liver metastases Total Bilirubin <=2.0 × ULN Creatinine <= 1.5 × ULN#1 or Creatinine Clearance (Cockcroft-Gault) > 60 mL/min #1: Note that if SOX therapy is selected in Part 2, the criterion for initiating SOX therapy is <= 1.2 × ULN; 9.Contraception for Women: Women of childbearing potential#2 must agree to use contraception#3 starting from the time of informed consent until at least 5 months after the last dose of study drug or combination chemotherapy, whichever is later. Additionally, women must agree not to breastfeed from the date of informed consent until at least 5 months after the last dose of study drug or combination chemotherapy, whichever is later. #2: Women of childbearing potential are defined as all women who have experienced menarche and are not postmenopausal or permanently sterilized (e.g., hysterectomy, bilateral tubal ligation, bilateral oophorectomy). Postmenopausal is defined as >=12 consecutive months of amenorrhea without an alternative medical cause. Women using oral contraceptives or mechanical contraception such as intrauterine devices and barrier methods are considered to have childbearing potential. 10.Contraception for Men: Male patients must agree to use contraception#3 starting from the initiation of study treatment until at least 7 months after the last dose of study drug or combination chemotherapy, whichever is later. #3: Patients must agree to use at least two of the following different contraceptive methods: For male patients or male partners of female patients: vasectomy or use of a condom; For female patients or female partners of male patients: tubal ligation, diaphragm, intrauterine device, and oral contraceptives.

排除标准：

1.已知的病变中有活动性出血的征象；
2.贲门或幽门梗阻，影响进食和胃排空，或导致吞咽片困难；
3.诊断为HER 2阳性G/GEJ AC；
4.肿瘤组织的免疫组化或分子学检测提示为dMMR/MSI-H；
5.既往有对晚期或转移性G/GEJ AC的全身治疗；
6.以前的新（辅助）治疗中，累积顺铂剂量≥300 mg/m2；
7.外周神经毒性在既往治疗后未消退到1级；
8.已知的二氢嘧啶脱氢酶（DPD）酶缺乏症（或氟尿嘧啶治疗前3级或更高的黏膜毒性）；
9.已知对任何单克隆抗体或化疗药物（卡培他滨和 / 或奥沙利铂）的成分过敏（既往出现过 3 级或以上过敏反应）；
10.既往曾使用过任何抗程序性死亡受体 1（anti -PD-1）或抗程序性死亡受体配体 1（anti -PD-L1）、抗程序性死亡受体配体 2（anti -PD-L2）、抗细胞毒性 T 淋巴细胞相关抗原 4（anti -CTLA-4）抗体，或任何其他特异性靶向 T 细胞共刺激或免疫检查点通路的抗体或药物；
11.既往有帕金森等可导致肢体震颤、共济失调的神经系统疾病；
12.既往有精神类疾病病史患者；
13.因特定原因（如同时患有痴呆症）而无法签署知情同意书；
14.纳入另一项介入性临床研究，除非只涉及观察性研究（非介入性）或介入性研究的随访阶段；
15.在第一剂研究药物使用前2周内接受中药治疗癌症适应症或免疫调节剂（包括胸腺素、干扰素和白细胞介素）的全身治疗；
16.在首次服用研究药物前 4 周内接受过免疫抑制药物治疗，但鼻用、吸入或其他局部途径使用的局部糖皮质激素，或生理剂量的全身性糖皮质激素（泼尼松不超过 10 毫克 / 天或等效剂量），或用于预防对造影剂过敏的糖皮质激素除外；
17.在第一剂研究药物使用前4周内接受减毒活疫苗，或计划在研究期间接受该疫苗。注：允许在第一剂研究药物使用前4周内接种季节性灭活流感病毒疫苗，但不允许接种流感减毒活疫苗；
18.在第一次服用研究药物前4周内接受大手术（开颅、开胸或剖腹手术），或在试验期间接受大手术；在第一次服用研究药物前2周内接受腹腔镜探查检查；
19.在首次服用研究药物前，抗肿瘤治疗相关的毒性反应（不包括脱发、无临床意义的事件或无症状的实验室检查异常）尚未恢复至美国国立癌症研究所不良事件通用术语标准（NCI CTCAE）第 5.0 版所规定的 0 级或 1 级；
20.已知存在有症状的中枢神经系统（CNS）转移和 / 或癌性脑膜炎。曾接受过脑转移治疗的患者，若病情稳定（在首次服用研究药物前至少 4 周的影像学检查无进展证据，且再次进行影像学检查时无新的脑转移灶或原发脑转移病灶无增大迹象），并且在首次服用研究药物前至少 14 天无需使用糖皮质激素，则符合入组条件。但癌性脑膜炎患者不在此例外情况之列，无论其病情是否在临床上处于稳定状态；
21.已导致呼吸功能障碍而需要引流的胸腔积液；
22.存在截瘫风险的骨转移患者；
23.已知或疑似患有自身免疫性疾病，或在过去 2 年内有这些疾病的病史（白癜风、银屑病、脱发或格雷夫斯病患者，若在 2 年内无需接受全身性治疗，或者仅需甲状腺激素替代治疗的甲状腺功能减退患者，以及仅需胰岛素替代治疗的 1 型糖尿病患者可以入组）。
24.已知的原发性免疫缺陷疾病病史；
25.已知患有活动性肺结核；
26.已知有同种异体器官移植或异基因造血干细胞移植史；
27.已知的人类免疫缺陷病毒病史（艾滋病毒检测呈阳性）；
28.活动性或临床控制不佳的严重感染；
29.有症状性充血性心力衰竭（NYHA II-IV级）或有症状性或控制不良的心律失常；
30.尽管经过规范治疗，但仍存在血压控制不佳的情况（收缩压≥160mmHg 或舒张压≥100mmHg）；
31.入组前 6 个月内发生过任何动脉血栓栓塞事件，包括心肌梗死、不稳定型心绞痛、脑血管意外或短暂性脑缺血发作；
32.存在严重营养不良情况（1 个月内体重减轻 5%，3 个月内体重减轻超过 15%，或在签署知情同意书前 1 周内食物摄入量减少 1/2 及以上），但在首次服用研究药物前已进行 4 周及以上营养不良纠正治疗的患者除外；
33.入组前 3 个月内有深静脉血栓、肺栓塞或其他严重血栓栓塞事件病史（植入式输液港或导管相关血栓形成，或浅表静脉血栓形成不被视为 “严重” 血栓栓塞）；
34.存在未得到控制的代谢紊乱、非恶性器官疾病或全身性疾病，或与癌症相关的继发性疾病，这些情况可能会导致更高的医疗风险和（或）生存评估的不确定性。
35.肝性脑病、肝肾综合征或肝硬化伴Child-PughB级或C级；
36.肿瘤相关肠梗阻（ICF签署前3个月内）或以下疾病病史：炎症性肠病或广泛肠切除术（部分结肠切除术或广泛小肠切除术伴慢性腹泻）、克罗恩病和溃疡性结肠炎；
37.已知的急性或慢性活动性乙型肝炎（HBsAg和HBV DNA病毒载量阳性≥200 IU/mL或≥103copey/mL），或急性或慢性活动性丙型肝炎（anti-HCV抗体阳性和HCV RNA阳性）；
38.已知的需要治疗的活动性梅毒感染；
39.入组前6个月内有胃肠道穿孔和/或瘘管病史，不包括因胃癌穿孔导致的原发性胃癌病变切除；
40.需要使用皮质类固醇（激素）治疗的间质性肺疾病；
41.其他原发性恶性肿瘤病史，不包括： 在入组前至少已达到完全缓解（CR）状态两年，且在研究期间无需接受任何治疗的恶性肿瘤患者。 已接受充分治疗且无疾病复发迹象的非黑色素瘤皮肤癌或恶性雀斑样痣。 经过充分治疗的原位癌，没有复发的迹象。
42.怀孕或哺乳期的女性患者；
43.存在急性或慢性疾病、精神障碍或实验室检查异常，且这些情况可能导致以下后果：增加与研究药物相关的风险，或干扰对研究结果的解读，并且经研究者判定不符合参与本研究的条件；

Exclusion criteria：

1.Known lesions with signs of active bleeding; 2.Gastric cardia or pyloric obstruction affecting food intake and gastric emptying, or causing difficulty swallowing whole tablets; 3.Diagnosis of HER2-positive gastric or gastroesophageal junction adenocarcinoma (G/GEJ AC); 4.Tumor tissue testing (immunohistochemistry or molecular testing) indicates deficient mismatch repair (dMMR) or microsatellite instability-high (MSI-H) status; 5.Prior systemic therapy for advanced or metastatic G/GEJ AC; 6.Cumulative cisplatin dose ≥ 300 mg/m2 from prior (neo)adjuvant therapy; 7.Peripheral neuropathy not resolved to Grade 1 or better after prior therapy; 8.Known complete deficiency of dihydropyrimidine dehydrogenase (DPD) enzyme (or history of Grade >=3 mucosal toxicity with prior fluoropyrimidine treatment); 9.Known hypersensitivity (history of Grade >=3 allergic reaction) to any monoclonal antibody or to any component of the chemotherapy agents (capecitabine and/or oxaliplatin); 10.Prior treatment with any anti-programmed cell death protein 1 (anti-PD-1), anti-programmed death-ligand 1 (anti-PD-L1), anti-programmed death-ligand 2 (anti-PD-L2), anti-cytotoxic T-lymphocyte-associated antigen 4 (anti-CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways; 11.History of neurological diseases such as Parkinson's disease that could cause tremors or ataxia; 12.History of psychiatric illness; 13.Inability to provide informed consent due to specific reasons (e.g., concurrent dementia); 14.Participation in another interventional clinical study, unless it is an observational (non-interventional) study or the follow-up phase of an interventional study; 15.Systemic treatment with traditional Chinese medicine for cancer indications or immunomodulators (including thymosin, interferons, interleukins) within 2 weeks prior to the first dose of study drug; 16.Treatment with immunosuppressive medication within 4 weeks prior to the first dose of study drug. Exceptions include intranasal, inhaled, or topical corticosteroids, or systemic corticosteroids at physiological doses (<=10 mg/day prednisone or equivalent), or corticosteroids used for prophylaxis of contrast agent allergy; 17.Receipt of live attenuated vaccine within 4 weeks prior to the first dose of study drug, or plans to receive such vaccine during the study. Note: Seasonal inactivated influenza vaccines are allowed; live attenuated influenza vaccines are not; 18.Major surgery (craniotomy, thoracotomy, or laparotomy) within 4 weeks prior to the first dose of study drug, or planned major surgery during the trial; laparoscopic examination within 2 weeks prior to the first dose of study drug; 19.Toxicity related to prior anti-tumor therapy (excluding alopecia, clinically non-significant events, or asymptomatic laboratory abnormalities) that has not recovered to Grade 0 or 1 as per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 prior to the first dose of study drug; 20.Known symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis. Patients with treated brain metastases are eligible if stable (no evidence of progression on imaging for at least 4 weeks prior to the first dose, with no new or enlarging metastases) and off systemic corticosteroids for at least 14 days prior to the first dose. Patients with carcinomatous meningitis are excluded regardless of clinical stability; 21.Pleural effusion causing respiratory compromise requiring drainage; 22.Patients with bone metastases at risk of spinal cord compression; 23.Known or suspected active autoimmune disease, or history of such disease within the past 2 years (patients with vitiligo, psoriasis, alopecia, or Graves' disease who have not required systemic treatment within the past 2 years, patients with hypothyroidism requiring only thyroid hormone replacement, and patients with Type 1 diabetes mellitus requiring only insulin replacement are allowed); 24.Known history of primary immunodeficiency; 25.Known active tuberculosis; 26.Known history of allogeneic organ transplant or allogeneic hematopoietic stem cell transplant; 27.Known history of human immunodeficiency virus (HIV) infection (positive HIV test); 28.Active or clinically uncontrolled severe infection; 29.Symptomatic congestive heart failure (NYHA Class II-IV) or symptomatic or uncontrolled arrhythmia; 30.Poorly controlled hypertension despite standard treatment (systolic blood pressure>=160 mmHg or diastolic blood pressure >=100 mmHg); 31.Any arterial thromboembolic event within 6 months prior to enrollment, including myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack; 32.Severe malnutrition (weight loss >=5% within 1 month, weight loss >15% within 3 months, or reduction in food intake by>=1/2 within the week prior to signing informed consent), unless corrective treatment for malnutrition has been ongoing for at least 4 weeks prior to the first dose of study drug; 33.History of deep vein thrombosis, pulmonary embolism, or other significant thromboembolic event within 3 months prior to enrollment (implanted port or catheter-related thrombosis, or superficial vein thrombosis are not considered "significant" thromboembolism); 34.Uncontrolled metabolic disorders, non-malignant organ disease, systemic disease, or secondary conditions related to cancer that could result in higher medical risk and/or uncertainty in survival assessment; 35.Hepatic encephalopathy, hepatorenal syndrome, or cirrhosis with Child-Pugh Class B or C; 36.Tumor-related bowel obstruction (within 3 months prior to signing ICF) or history of the following conditions: inflammatory bowel disease requiring medical intervention (e.g., Crohn's disease, ulcerative colitis), or extensive bowel resection (partial colectomy or extensive small bowel resection with chronic diarrhea); 37.Known acute or chronic active hepatitis B (HBsAg positive and HBV DNA viral load >=200 IU/mL or >= 103 copies/mL), or acute or chronic active hepatitis C (anti-HCV antibody positive and HCV RNA positive); 38.Known active syphilis infection requiring treatment; 39.History of gastrointestinal perforation and/or fistula within 6 months prior to enrollment, excluding resection of the primary gastric cancer lesion that had presented with perforation; 40.Interstitial lung disease requiring corticosteroid treatment; 41.History of another primary malignancy, except: Malignancy treated with curative intent and in complete remission for at least 2 years prior to enrollment, with no additional treatment required during the study period. Non-melanoma skin cancer or lentigo maligna with adequate treatment and no evidence of disease recurrence. Carcinoma in situ adequately treated with no evidence of recurrence; 42.Pregnant or breastfeeding female patients; 43.Presence of any acute or chronic medical condition, psychiatric disorder, or laboratory abnormality that could increase the risk associated with study participation, interfere with the interpretation of study results, or, in the judgment of the investigator, make the patient inappropriate for entry into this study.

研究实施时间：

Study execute time：

从 From 2026-01-01 00:00:00至 To 2029-12-31 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2026-04-01 00:00:00 至 To 2029-12-31 00:00:00

干预措施：

Interventions：

组别：

试验组

样本量：

 30

Group：

Experimental group

Sample size：

干预措施：

不同剂量司替戊醇联合抗PD-1单抗+XELOX方案

干预措施代码：

Intervention：

Combination of varying doses of stiripentol with anti-PD-1 antibody and the XELOX regimen（Oxaliplatin 130 mg/m2 IV on day 1 + Capecitabine 1000 mg/m）.

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 广东 

市(区县)：

  

Country：

China

Province：

Guangdong

City：

单位(医院)：

 中山大学附属第七医院 

单位级别：

 三级甲等 

Institution
hospital：

The Seventh Affiliated Hospital of Sun Yat-sen University

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

最大耐受剂量（MTD）

指标类型：

主要指标

Outcome：

Maximum tolerated dose

Type：

Primary indicator

测量时间点：

观察期自用药开始至第二个用药疗程结束后7天

测量方法：

我们选用BMA-POCRM （TITE-BMA-POCRM）模型进行递增，剂量递增以3例患者为队列单位持续进行，直至研究入组满30例患者（或因安全性问题提前终止）。每完成一队列后，将运行上述模型并确定下一队列的推荐剂量。最后一队列患者完成观察后，将最终确定推荐的最大耐受剂量。

Measure time point of outcome：

The observation period runs from the start of medication to 7 days after the second course ends.

Measure method：

We will use the BMA-POCRM （TITE-BMA-POCRM）model for dose escalation. Escalation will proceed continuously in cohorts of 3 patients until a total of 30 patients have been enrolled (or the study is terminated early due to safety concerns). After each cohort is completed, the model will be run to determine the recommended dose for the next cohort. After the last cohort of patients has completed observation, the recommended maximum tolerated dose (MTD) will be definitively determined.

指标中文名：

总体生存（OS）

指标类型：

次要指标

Outcome：

Overall survival

Type：

Secondary indicator

测量时间点：

治疗期每个周期评估，之后每3个月随访评估。

测量方法：

自接受治疗之日起，通过门诊复查、电话随访等方式追踪患者生存状态。治疗期间持续记录，治疗结束后每3个月随访一次，直至死亡、失访或研究结束。死亡事件以死亡证明或官方记录中的死亡日期为准。

Measure time point of outcome：

Evaluated each cycle on-treatment, then every 3 months.

Measure method：

Patient survival status is tracked from the date of treatment through outpatient follow-ups and telephone interviews. Data is continuously recorded during the treatment period, with follow-up assessments every three months after treatment completion until death, loss to follow-up, or study conclusion. The date of death is determined based on death certificates or official records.

指标中文名：

药代动力学（PK）

指标类型：

次要指标

Outcome：

Pharmacokinetics

Type：

Secondary indicator

测量时间点：

用药第7日、第14日服药前及服药后3小时。患者出现2级及以上神经、精神系统症状时都需测定即时血药浓度。

测量方法：

抽取外周血，通过试剂盒进行检测。

Measure time point of outcome：

Dose on days 7 & 10: pre- & 3h post-dose. Immediate upon grade ≥2 neuropsychiatric symptoms

Measure method：

Peripheral blood is drawn and tested using a commercial kit.

指标中文名：

无进展生存（PFS）

指标类型：

次要指标

Outcome：

Progress-free survival

Type：

Secondary indicator

测量时间点：

开始治疗日期开始，到首次记录到疾病进展或因任何原因死亡为止。

测量方法：

按RECIST标准定期影像学复查，记录PD或死亡。

Measure time point of outcome：

From the start of treatment to the first documented disease progression or death from any cause.

Measure method：

Regular imaging follow-up per RECIST criteria to document PD or death.

指标中文名：

疾病控制率（DCR）

指标类型：

次要指标

Outcome：

Disease control rate

Type：

Secondary indicator

测量时间点：

2个治疗周期后

测量方法：

通过影像学等评估手段。

Measure time point of outcome：

After 2 treatment cycles.

Measure method：

Through imaging and other evaluation methods.

指标中文名：

缓解持续时间（DoR）

指标类型：

次要指标

Outcome：

Duration of relief

Type：

Secondary indicator

测量时间点：

从首次确认缓解（CR/PR）直至疾病进展或死亡。

测量方法：

按RECIST标准定期影像学复查，记录PD或死亡。

Measure time point of outcome：

From first confirmed response (CR/PR) until disease progression or death.

Measure method：

Regular imaging follow-up per RECIST criteria to document PD or death.

采集人体标本：

Collecting sample(s)
from participants：

标本中文名：

肿瘤活检

组织：

Sample Name：

Tumor biopsy

Tissue：

人体标本去向

 使用后保存  

说明

Fate of sample：

Preservation after use  

Note：

标本中文名：

血液标本

组织：

Sample Name：

Blood sample

Tissue：

人体标本去向

 使用后保存  

说明

Fate of sample：

Preservation 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:

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：

运用电子数据采集系统/病例报告表

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

Electronic data capture system/case report form was used

数据与安全监察委员会：

Data and Safety Monitoring Committee：

无/No

注册人：

Name of Registration：

  2026-04-01 10:44:01