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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Gastric Cancer; Cryoballoon Ablation
• Intervention / Treatment: Procedure: Endoscopic Cryoballoon Ablation Treatment; Drug: PD1 Inhibitor

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.

• Study Type: Interventional
• Enrollment (Estimated): 42
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200000
      • Huashan Hospital, Fudan University, Shanghai
      • Contact: Wanwei Zheng; Phone Number: +86 13816431448; Email: calebzww@yeah.net

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 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;
2. Age ≥18 years;
3. WHO pathological types: adenocarcinoma or neuroendocrine tumors;
4. Physician-assessed estimated life expectancy greater than 3 months, with distant metastases considered controllable;
5. Maximum diameter of the primary tumor ≤6 cm;
6. 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;
7. Hematological criteria: hemoglobin (Hgb) ≥70 g/L; absolute neutrophil count (ANC) ≥1.5×10⁹/L; platelet count (PLT) ≥80×10⁹/L;
8. Coagulation function: prothrombin time (PT) and activated partial thromboplastin time (APTT) both <2 times the normal value;
9. Negative pregnancy test for women of childbearing potential;
10. Eastern Cooperative Oncology Group (ECOG) performance status ≤2;
11. Signed informed consent form.

Exclusion Criteria:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ECAT + PD-1; Patients who achieve a partial response (PR) following standard treatment will subsequently receive gastric local endoscopic cryoballoon ablation treatment (ECAT) combined with sintilimab. Sintilimab will be administered within three days before and after the ECAT procedure, and continued regularly thereafter.	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 subsequent treatment was given every three weeks according to the instructions.; Other Names: ECAT; 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.
Active Comparator: PD-1; The remaining 10 patients who achieve a partial response (PR) following standard treatment will receive sintilimab monotherapy, followed by standard maintenance therapy.	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)	PFS is measured from the start of treatment until the first documented evidence of disease progression (based on RECIST 1.1) or death from any cause, whichever occurs first.	From enrollment to study completion, assessed up to 2 years
Overall-Survival (OS)	The length of time from the start of treatment until death from any cause.	From enrollment to study completion, assessed up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of participants achieving complete remission (CR) and partial remission (PR) after treatment	Objective remission rate (ORR), the percentage of participants whose tumors shrink by a certain amount and remain there for a certain period of time, including complete remission (CR) and partial remission (PR). CR (Complete remission): Complete disappearance of the target lesion, with no new lesions produced, and lasting for more than 4 weeks. PR (Partial remission): the sum of the largest diameters of the target lesions is reduced by more than 30%, and lasts for more than 4 weeks.	3 to 24 weeks after the end of treatment
Percentage of participants achieving remission (PR+CR) and lesion stabilization (SD) after treatment	Disease control rate (DCR) is the percentage of participants who achieve remission (PR+CR) and stabilization of lesions (SD) after the treatment. Stable disease (SD) means that the sum of the largest diameters of the tumor lesions has not shrunk to PR, or has not enlarged to PD.	3 to 24 weeks after the end of treatment
Number of participants with treatment-related adverse events	The number of patients who experience ECAT-related adverse events (such as intraoperative bleeding, intraoperative perforation, postoperative bleeding, etc.)	From the start of treatment to 24 weeks after the end of treatment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of immune cells in peripheral blood	Peripheral blood will be analyzed for the number of immune cells after applying flow cytometry and mRNA sequencing.	From enrollment to study completion, assessed up to 24 weeks
Number of immune cells in tumor tissues	Apply mRNA sequencing, immunohistochemistry and immunofluorescence to analyze the number of immune cells in tumor tissues, including CTL, Treg, DC, TAM, MDSC, NK, NKT and so on.	From enrollment to study completion, assessed up to 24 weeks

Collaborators and Investigators

• Sponsor: Zhongguang Luo, MD

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2025
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): May 1, 2027

Study Registration Dates

• First Submitted: April 27, 2025
• First Submitted That Met QC Criteria: April 27, 2025
• First Posted (Actual): May 6, 2025

Study Record Updates

• Last Update Posted (Actual): May 6, 2025
• Last Update Submitted That Met QC Criteria: April 27, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: PD-1; Cryoballoon ablation; ECAT
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Antineoplastic Agents, Immunological; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Immune Checkpoint Inhibitors
• Other Study ID Numbers: KY2025-081

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No