A Randomized Controlled Study of Endoscopic Cryoablation Combined With PD-1 Inhibitor for Maintenance Therapy in Advanced Gastric Cancer

Overview

This study evaluates the safety and efficacy of endoscopic cryoballoon ablation treatment (ECAT) combined with a PD-1 inhibitor (sintilimab) as maintenance therapy in patients with advanced gastric cancer, and further explores the underlying immunoregulatory mechanisms.

Detailed description

This study is a single-center, randomized, controlled, open-label, prospective clinical trial. A total of 42 patients with advanced gastric cancer will be enrolled. Among them, 30 patients who achieve a partial response (PR) after receiving standard of care (SOC) treatment - such as FOLFOX, POLF, FLOT, SOX, CAPOX, or FOLFIRI - will be randomly assigned to two groups. Twenty patients will receive local gastric endoscopic cryoballoon ablation treatment (ECAT) combined with sintilimab, while the remaining ten patients will receive sintilimab monotherapy. Both groups will subsequently undergo standard maintenance therapy, followed by assessments of treatment efficacy, safety, and immunological evaluations of both peripheral blood and tumor tissues. Patients whose disease status is assessed as stable disease (SD) or progressive disease (PD) after SOC treatment will proceed to receive standard second-line therapies.

Interventions

• Procedure Endoscopic Cryoballoon Ablation Treatment
  ECAT: A cryoballoon with catheter is inserted along the endoscopic forceps channel, the balloon is placed on the surface of the tumor, and the balloon is dilated so that it fits snugly over the lesion. The freezing cycle is initiated and continued for 2-3 minutes, and then the balloon is rewarmed and frozen again for 2-3 minutes; the freeze-rewarm cycle is repeated twice. PD-1:The first PD-1 monoclonal antibody treatment in this study was given within 3 days before and after ECAT treatment, and
• Drug PD1 Inhibitor
  The first administration of the PD-1 monoclonal antibody is initiated when patients achieve a partial response (PR) following standard treatment. Subsequent administrations are given every three weeks according to the prescribing information.

Primary outcome measures

• Progression-Free Survival (PFS) [Time frame: From enrollment to study completion, assessed up to 2 years]
• Overall-Survival (OS) [Time frame: From enrollment to study completion, assessed up to 5 years]

Secondary outcome measures (3)

• Percentage of participants achieving complete remission (CR) and partial remission (PR) after treatment [Time frame: 3 to 24 weeks after the end of treatment]
• Percentage of participants achieving remission (PR+CR) and lesion stabilization (SD) after treatment [Time frame: 3 to 24 weeks after the end of treatment]
• Number of participants with treatment-related adverse events [Time frame: From the start of treatment to 24 weeks after the end of treatment]

Eligibility criteria

Inclusion criteria

• Patients diagnosed with advanced gastric cancer (stage IV according to the AJCC 8th edition, including locally advanced unresectable gastric cancer \[stage IVa\] and gastric cancer with distant metastasis \[stage IVb\]; Borrmann classification types I, II, or III) who are deemed ineligible for surgical resection or unable to tolerate surgery, and meet the indications for first-line therapy with sintilimab combined with fluoropyrimidine- and platinum-based chemotherapy;
• Age ≥18 years;
• WHO pathological types: adenocarcinoma or neuroendocrine tumors;
• Physician-assessed estimated life expectancy greater than 3 months, with distant metastases considered controllable;
• Maximum diameter of the primary tumor ≤6 cm;
• Adequate major organ function, defined as:① Liver function: ALT and AST ≤ 2.5 times the positive range, total bilirubin ≤ 2.0mg/dL; ② Renal function: creatinine clearance ≥ 40mL/min calculated using the EPI formula;
• Hematological criteria: hemoglobin (Hgb) ≥70 g/L; absolute neutrophil count (ANC) ≥1.5×10⁹/L; platelet count (PLT) ≥80×10⁹/L;
• Coagulation function: prothrombin time (PT) and activated partial thromboplastin time (APTT) both <2 times the normal value;
• Negative pregnancy test for women of childbearing potential;
• Eastern Cooperative Oncology Group (ECOG) performance status ≤2;
• Signed informed consent form.

Exclusion criteria

• Pregnant or breastfeeding women, or women planning to become pregnant within six months;
• Patients with infectious diseases (such as HIV, syphilis, or active tuberculosis);
• Patients with active hepatitis B or hepatitis C infection;
• Patients with other concurrent primary malignancies;
• Patients who have participated in another clinical trial within the past month;
• Patients who have taken antiplatelet or anticoagulant medications within the past week;
• Patients with gastric cancer complicated by active bleeding;
• Patients with massive ascites (ascites volume ≥3000 mL);
• Patients with cardia obstruction or pyloric obstruction;
• Patients with active infections or autoimmune diseases;
• Patients deemed unsuitable for treatment by the investigator for any other reason.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Huashan Hospital, Fudan University, Shanghai — Shanghai

Identifiers

NCT: NCT06957977 · KY2025-081

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗