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A Sequential Trial of Low-Dose Radiotherapy Followed by Concurrent Immunotherapy, Systemic Chemotherapy, and Intraperitoneal Perfusion in Gastric Cancer With Peritoneal Carcinomatosis

2026年8月21日 更新者:Ying Jieer、Zhejiang Cancer Hospital
This study is a prospective, single-center, open-label, exploratory phase II clinical trial aimed at evaluating the safety, tolerability, and preliminary efficacy of low-dose radiotherapy (LDR) sequentially combined with serplulimab, bevacizumab analog, and irinotecan or albumin-bound paclitaxel in patients with gastric cancer and peritoneal metastases. A total of 40 patients with gastric adenocarcinoma who have previously undergone first-line therapy are planned for enrollment. Patients will be grouped based on prior exposure to paclitaxel-based chemotherapy to determine whether they will receive systemic treatment with irinotecan combined with serplulimab or albumin-bound paclitaxel combined with serplulimab, along with local intraperitoneal infusion of bevacizumab analog. The study adopts a Simon two-stage design, with 20 patients enrolled in the first stage. If ≥3 patients achieve objective remission, the study will proceed to the second stage, enrolling an additional 20 patients.

研究概览

详细说明

In China, most gastric cancer patients are diagnosed at an advanced stage. The peritoneum is the most common site of metastasis for gastric cancer, representing a specific mode of metastasis. Based on cytology of abdominal cavity dropout cells and peritoneal implantation formation, it can be classified into CY1P0, CY1P1, and CY0P1 types. Approximately 20% of patients are diagnosed with peritoneal metastasis preoperatively or intraoperatively, and more than 50% of T3 and T4 stage patients develop peritoneal metastasis after radical surgery. Peritoneal metastasis often leads to malignant ascites, intestinal obstruction, cancer pain, and other complications, severely affecting the quality of life of patients. According to epidemiological data, in 2020, the number of gastric cancer patients with peritoneal metastasis in China reached 523,937 cases 3-6 months, and a 5-year survival rate of less than 2% . Effective control of ascites in gastric cancer patients can not only improve their quality of life but also effectively extend their survival time. The survival period for first-line gastric cancer patients with peritoneal metastasis has increased from 3-6 months with traditional chemotherapy to 12-22 months with comprehensive treatment , but the efficacy for second-line gastric cancer patients with peritoneal metastasis remains limited, and more effective treatment regimens are still needed.

Vascular endothelial growth factor (VEGF) plays a central role in angiogenesis and ascites formation in peritoneal metastases. Research evidence shows that intraperitoneal infusion of anti-VEGF drugs, such as bevacizumab, can effectively control ascites and prolong the time to ascites recurrence. When combined with the immune checkpoint inhibitor sintilimab, the ascites control rate can reach 91%, with partial reduction of peritoneal metastases by more than 30% in some patients. Analysis of immune cells in ascites showed that the CD8+/Treg ratio increased threefold after treatment (P<0.01), and immunohistochemistry results from peritoneal biopsy indicated upregulation of PD-L1 expression in the combination therapy group (combination group vs baseline: +45% vs +10%), suggesting that blocking VEGF can normalize tumor vasculature, reverse the immunosuppressive microenvironment, enhance T-cell infiltration, and exert synergistic effects study, are actively exploring whether combining immunotherapy with VEGFR inhibitors and chemotherapy can improve survival, but further investigation is still needed.

Recent research findings indicate that low-dose radiation therapy (Low-Dose Radiation, LDR, single dose ≤1 Gy) exhibits distinct biological effects compared to conventional radiation therapy (fractionated dose1.8-3 Gy)20.LDR not only does not cause significantDNA double-strand breaks and apoptosis but also remodels the tumor microenvironment by activating various immune-related pathways.

Based on the aforementioned background, this study proposes an innovative combination therapy strategy: low-dose radiotherapy (LDR) followed by immunochemotherapy. The core mechanisms are as follows: (1) Immune initiation effect: LDR acts as an "immune initiator," inducing immunogenic cell death and activating antigen-presenting cells. The peak of immune activation occurs 24-72 hours after LDR, during which administration of the PD-1 inhibitor (serplulimab) can maximize synergistic effects. (2) Vascular normalization window: A peak in vascular normalization is observed 7-14 days after LDR treatment. Combining anti-VEGF drugs (bevacizumab analog) can maintain the vascular normalization state and improve the distribution of chemotherapeutic drugs in metastases to the peritoneum. (3) Overcoming chemotherapy resistance: LDR downregulates the expression of DNA repair genes in tumor cells, enhancing the cytotoxic action of irinotecan and albumin-bound paclitaxel. Preclinical studies show that 0.5 Gy radiotherapy can increase the concentration of paclitaxel in metastases to the peritoneum by 2.8 times.

This study selected low-dose radiotherapy combined with intraperitoneal infusion of bevacizumab. Based on whether first-line chemotherapy regimens included intravenous chemotherapy with albumin-bound paclitaxel, patients were chosen to receive second-line systemic treatment with irinotecan/albumin-bound paclitaxel combined with serplulimab. The study explores the approach of immune rechallenge and low-dose radiotherapy sequential systemic treatment combined with intraperitoneal infusion therapy, aiming to provide new therapeutic strategies and methods for second-line patients with gastric cancer accompanied by peritoneal metastasis.

研究类型

介入性

注册 (估计的)

40

阶段

  • 阶段2

联系人和位置

本节提供了进行研究的人员的详细联系信息,以及有关进行该研究的地点的信息。

学习联系方式

  • 姓名:Qi Xu, Master
  • 电话号码:+86-15205813046
  • 邮箱:zjhzxuqi@163.com

学习地点

    • Zhejiang
      • Hangzhou、Zhejiang、中国、310022
        • Zhejiang Cancer Hospital
        • 接触:

参与标准

研究人员寻找符合特定描述的人,称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

  • 成人
  • 年长者

接受健康志愿者

不

描述

Inclusion Criteria:

  • 1. Age >18 years on the day of signing the Informed Consent Form; 2. The subject is able to comprehend the procedures and methods of this clinical study, and voluntarily signs the informed consent form after providing full informed consent.

    3. Gastric or gastroesophageal junction adenocarcinoma (HER2-negative) confirmed by histology or cytology.

    4. Imaging confirmed metastases to peritoneum (PCI score ≥10), not suitable for radical excision 5. Failure of first-line platinum-based chemotherapy (due to progression or inability to tolerate).

    6. CT imaging or PET CT suggests metastases to the peritoneum, or ascites cytology is positive.

    7. ECOG PS 0-2, expected survival ≥3 months. 8. Organ function meets the following criteria (within 10 days of first receiving the investigational medicinal product).

    1. Hematology: Platelet count ≥100×10⁹/L, hemoglobin ≥8g/dL, ANC ≥1.5×10⁹/L, and no blood products, erythropoiesis-stimulating agents, or colony-stimulating factors therapy received within the past 7 days;
    2. Renal function: Serum creatinine is within the normal upper limit range set by the institution;
    3. Liver function: Total bilirubin ≤ 1.5×UNL; if total bilirubin > 1.5×UNL, then direct bilirubin should be ≤ UNL, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) both ≤ 2.5×UNL, albumin > 2.5 mg/dL;
    4. Coagulation function: International normalized ratio (INR), prothrombin time (PT), activated partial thromboplastin time (APTT) ≤1.5×UNL; if the subject is undergoing anticoagulation therapy, it should be within the established therapeutic range; 9. Women of childbearing age must have a negative serum pregnancy test within 72 hours prior to the first administration of the investigational medicinal product. If the urine test result is positive or cannot be confirmed as negative, further serum pregnancy testing is required.

      10. Women of childbearing age must agree to use two effective methods of birth control or undergo surgical sterilization, or choose to avoid any heterosexual intercourse throughout the study period and for 120 days after the last drug administration. (Women who have been postmenopausal for more than one year and have not undergone surgical sterilization are considered infertile.) Lactating women must cease breastfeeding.

      11. Male subjects should agree to adopt effective contraceptive measures from the first administration until 120 days after the final administration.

      Exclusion Criteria:

  • 1. Presence of active metastases to the central nervous system or meningitis carcinomatosa.

    2. There is an uncontrolled abdominal infection, intestinal obstruction, grade 3 abdominal effusion, or risk of gastrointestinal fistula and perforation.

    3. Study participants received systemic immunosuppressant therapy within 28 days prior to treatment.

    4. Known to be allergic to any investigational product or any excipient of the investigational product.

    5. Diagnosed with other malignancies within the past 5 years, and the tumor is currently in a progressive stage or requires therapy (excluding basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or cervical carcinoma in situ that has undergone potential radical treatment).

    6. There is active autoimmune disease, and systemic therapy (including the use of disease-modifying drugs, corticosteroids, or immunosuppressants) has been received in the past two years. Replacement therapy (e.g., thyroxine replacement for hypothyroidism, insulin therapy for diabetes, or physiological glucocorticoid supplementation for adrenal/pituitary insufficiency) is not considered systemic therapy.

    7. Previously suffered from (non-infectious) pneumonia requiring glucocorticoid therapy, or currently suffering from pneumonia.

    8. There is an active infection requiring systemic therapy. 9. The presence of any history of disease, therapy, or laboratory abnormalities that could potentially interfere with the test results, affect the subject's full participation, or be deemed unsuitable for the subject's participation in the study by the Sub investigator.

    10. Past or current presence of mental disease or drug abuse, deemed by the sub investigator as unable to comply with trial requirements.

    11. Already pregnant or in lactation, or plans to become pregnant or cause pregnancy during the trial period (from the start of pre-screening or screening visit to 120 days after the final administration).

    12. Known infection with Human Immunodeficiency Virus (HIV1/2 antibody positive).

    13. Known to have hepatitis B (e.g., HBV Hepatitis B Surface Antigen positive) or hepatitis C (e.g., HCV RNA test positive).

    14. Received any live vaccine within 30 days prior to the first use of the investigational medicinal product.

学习计划

本节提供研究计划的详细信息,包括研究的设计方式和研究的衡量标准。

研究是如何设计的?

设计细节

  • 主要用途:治疗
  • 分配:不适用
  • 介入模型:单组作业
  • 屏蔽:无(打开标签)

武器和干预

参与者组/臂
干预/治疗
实验性的:Experimental Group
low-dose radiotherapy (LDR) sequentially combined with serplulimab, bevacizumab analog, and irinotecan or albumin-bound paclitaxel group
low-dose radiotherapy (LDR) sequentially combined with serplulimab, bevacizumab analog, and irinotecan or albumin-bound paclitaxel

研究衡量的是什么?

主要结果指标

结果测量
措施说明
大体时间
无进展生存期
大体时间:12个月
无进展生存期
12个月

次要结果测量

结果测量
措施说明
大体时间
操作系统
大体时间:36个月
总生存期
36个月
反应率
大体时间:12个月
客观反应率
12个月
DCR
大体时间:12个月
疾病控制率
12个月
DOR
大体时间:36 months
Duration of remission
36 months
Safety assessment
大体时间:36 months
TEAEs
36 months

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

调查人员

  • 学习椅:Qi Xu, Master、Zhejiang Cancer Hospital

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查,以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (估计的)

2026年9月1日

初级完成 (估计的)

2028年9月1日

研究完成 (估计的)

2029年7月30日

研究注册日期

首次提交

2026年8月21日

首先提交符合 QC 标准的

2026年8月21日

首次发布 (实际的)

2026年8月25日

研究记录更新

最后更新发布 (实际的)

2026年8月25日

上次提交的符合 QC 标准的更新

2026年8月21日

最后验证

2026年8月1日

更多信息

与本研究相关的术语

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)?

不

药物和器械信息、研究文件

研究美国 FDA 监管的药品

不

研究美国 FDA 监管的设备产品

不

此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.

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