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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

21 de agosto de 2026 actualizado por: 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.

Descripción general del estudio

Descripción detallada

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.

Tipo de estudio

Intervencionista

Inscripción (Estimado)

40

Fase

  • Fase 2

Contactos y Ubicaciones

Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.

Estudio Contacto

  • Nombre: Qi Xu, Master
  • Número de teléfono: +86-15205813046
  • Correo electrónico: zjhzxuqi@163.com

Ubicaciones de estudio

    • Zhejiang
      • Hangzhou, Zhejiang, Porcelana, 310022
        • Zhejiang Cancer Hospital
        • Contacto:

Criterios de participación

Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.

Criterio de elegibilidad

Edades elegibles para estudiar

  • Adulto
  • Adulto Mayor

Acepta Voluntarios Saludables

No

Descripción

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.

Plan de estudios

Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.

¿Cómo está diseñado el estudio?

Detalles de diseño

  • Propósito principal: Tratamiento
  • Asignación: N / A
  • Modelo Intervencionista: Asignación de un solo grupo
  • Enmascaramiento: Ninguno (etiqueta abierta)

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
Experimental: 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

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
SLP
Periodo de tiempo: 12 meses
Supervivencia libre de progresión
12 meses

Medidas de resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Sistema operativo
Periodo de tiempo: 36 meses
Sobrevivencia promedio
36 meses
TRO
Periodo de tiempo: 12 meses
Tasa de respuesta objetiva
12 meses
DCR
Periodo de tiempo: 12 meses
Tasa de Control de la Enfermedad
12 meses
DOR
Periodo de tiempo: 36 months
Duration of remission
36 months
Safety assessment
Periodo de tiempo: 36 months
TEAEs
36 months

Colaboradores e Investigadores

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

Investigadores

  • Silla de estudio: Qi Xu, Master, Zhejiang Cancer Hospital

Fechas de registro del estudio

Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados ​​por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.

Fechas importantes del estudio

Inicio del estudio (Estimado)

1 de septiembre de 2026

Finalización primaria (Estimado)

1 de septiembre de 2028

Finalización del estudio (Estimado)

30 de julio de 2029

Fechas de registro del estudio

Enviado por primera vez

21 de agosto de 2026

Primero enviado que cumplió con los criterios de control de calidad

21 de agosto de 2026

Publicado por primera vez (Actual)

25 de agosto de 2026

Actualizaciones de registros de estudio

Última actualización publicada (Actual)

25 de agosto de 2026

Última actualización enviada que cumplió con los criterios de control de calidad

21 de agosto de 2026

Última verificación

1 de agosto de 2026

Más información

Términos relacionados con este estudio

Plan de datos de participantes individuales (IPD)

¿Planea compartir datos de participantes individuales (IPD)?

NO

Información sobre medicamentos y dispositivos, documentos del estudio

Estudia un producto farmacéutico regulado por la FDA de EE. UU.

No

Estudia un producto de dispositivo regulado por la FDA de EE. UU.

No

Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .

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