Irinotecan Liposome II + 5-FU/LV + Oxaliplatin + Karelizumab in Neoadjuvant Treatment of Gastric Cancer

A Single-arm Clinical Study of Irinotecan Liposome II + 5-FU/LV + Oxaliplatin + Karelizumab for Neoadjuvant Treatment of Gastric Cancer

For non-esophagogastric union progressive gastric cancer, the current treatment standard is D2 surgical resection combined with postoperative adjuvant chemotherapy, and for those with advanced stage (clinical stage III or above), perioperative chemotherapy mode can be chosen. For progressive esophagogastric combination cancer, neoadjuvant radiotherapy or preoperative chemotherapy can be chosen. Preoperative chemotherapy significantly improves the tumor remission rate and R0 resection rate with good safety. Irinotecan has been widely used in clinical practice, and together with the available data from the Irinotecan Liposome (II) clinical study demonstrated good safety and clinical efficacy, bringing hope for prolonging progression-free survival and overall survival for several tumor patients. In order to further explore the safety and efficacy of the neoadjuvant therapeutic application of irinotecan liposome (II) in patients with gastric cancer, the present study was conducted to provide data to guide future clinical practice.

Study Overview

• Status: Not yet recruiting
• Conditions: Gastric Cancer
• Intervention / Treatment: Drug: Irinotecan Liposomal

• Study Type: Interventional
• Enrollment (Estimated): 33
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yongxu Jia, M.D.; Phone Number: 15237128281; Email: fccjiayx@zzu.edu.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. age ≥ 18 years and ≤ 75 years;
2. gastric cancer confirmed by histopathology or cytology;
3. critically resectable gastric cancer confirmed by imaging;
4. at least one measurable lesion (according to RECIST v1.1);
5. ECOG score of 0 to 2;
6. expected survival time ≥ 3 months;
7. UGTA1*1*28 and UGTA1*1*6 genes tested wild-type;
8. bone marrow function: neutrophils (ANC) ≥1.5×10^9/L, platelets (PLT) ≥100×10^9/L, hemoglobin (Hb) ≥90g/L, white blood cells (WBC) ≥3.0×10^9/L;
9. Liver function: alanine aminotransferase (ALT), alanine transaminase (AST), alkaline phosphatase (ALP) ≤2.5×ULN (upper limit of normal), ≤5×ULN in case of liver metastasis; total bilirubin ≤1.5×ULN;
10. renal function: serum creatinine (Cr) ≤1.5×ULN or creatinine clearance ≥60 ml/min (calculated according to Cockroft-Gault), urine protein <2+;
11. coagulation: international normalized ratio (INR) ≤ 1.5 times upper limit of normal (ULN) and activated partial thromboplastin time (APTT) ≤ 1.5 times upper limit of normal (ULN);
12. be able to understand the circumstances of this study, and the patient and/or legal representative voluntarily agree to participate in this trial and sign the informed consent form.

Exclusion Criteria:

1. patients who have had other malignant tumors within the previous 5 years (except cured carcinoma in situ and basal cell carcinoma of the skin);
2. prior irinotecan/irinotecan liposome-based chemotherapy;
3. large pleural effusions or ascites requiring intervention;
4. active, uncontrolled bacterial, viral or fungal infections requiring systemic therapy
5. known active HIV infection; untreated active HBV and HCV infection
6. a combination of uncontrolled systemic diseases, including cardiovascular diseases such as unstable angina pectoris, myocardial infarction, congestive heart failure, severe unstable ventricular arrhythmia, and a history of severe pericardial disease; uncontrollable hypertension (defined as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg after regulated antihypertensive medication) or a history of critical hypertension, hypertensive encephalopathy; uncontrollable diabetes; and controlled diabetes mellitus, etc;
7. the presence of severe gastrointestinal-like illness (including active bleeding, greater than grade 1 obstruction, greater than grade 1 diarrhea, or gastrointestinal perforation)
8. history of cesarean section, open thoracic surgery or bowel resection within 28 days prior to enrollment;
9. presence of interstitial pneumonia or pulmonary fibrosis;
10. known hypersensitivity or intolerance to therapeutic drugs or their excipients;
11. history of pulmonary hemorrhage/coughing up ≥ grade 2 (defined as at least 2.5 mL of bright red blood) within 1 month prior to enrollment;
12. presence of arterial embolism, severe hemorrhage (other than hemorrhage due to surgery), or a predisposition to existing embolism or severe hemorrhage within 6 months prior to enrollment
13. presence of central nervous system metastases;
14. the presence of serum albumin ≤ 3 g/dL
15. those using strong inhibitors or inducers of CYP3A4, CYP2C8 and UGT1A1;
16. women who are pregnant or breastfeeding, and patients of childbearing potential who refuse to use adequate contraception during the course of this trial (from study enrollment to the end of primary study focus or surgical treatment);
17. who have participated in another study within 30 days prior to the administration of the first dose of study drug
18. patients who, in the judgment of the investigator, are not suitable for participation in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Irinotecan liposomal+5-FU/Calcium folinate+Oxaliplatin+Karelizumab; FOLFIRINOX + Karelizumab Irinotecan liposomal: 60 mg/m2, IV infusion, d1; 5-FU: 400 mg/m2, IV infusion, d1, followed by 1200 mg/m2/d x 2 days of continuous IV infusion (total 2400 mg/m2, 46-48h infusion); Calcium folinate: 400 mg/m2, IV infusion, d1; Oxaliplatin: 85 mg/m2, IV infusion, d1; Karelizumab: 200 mg, IV infusion, d1; Repeat every 2 weeks.

Drug: Irinotecan Liposomal; FOLFIRINOX + Karelizumab Irinotecan liposomal: 60 mg/m2, IV infusion, d1; 5-FU: 400 mg/m2, IV infusion, d1, followed by 1200 mg/m2/d x 2 days of continuous IV infusion (total 2400 mg/m2, 46-48h infusion); Calcium folinate: 400 mg/m2, IV infusion, d1; Oxaliplatin: 85 mg/m2, IV infusion, d1; Karelizumab: 200 mg, IV infusion, d1; Repeat every 2 weeks.; Other Names: 5-FU; Oxaliplatin; Calcium folinate; Karelizumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MPR	Rate of remission of major pathologies	After completion of 3 cycle of neoadjuvant therapy (through study completion, an average of half a year)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pCR	Pathologic complete remission rate	After completion of 3 cycle of neoadjuvant therapy (through study completion, an average of half a year)
R0 removal rate	R0 removal rate	After completion of 3 cycle of neoadjuvant therapy (through study completion, an average of half a year)

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Zhengzhou University

Study record dates

Study Major Dates

• Study Start (Estimated): August 15, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: July 8, 2025
• First Submitted That Met QC Criteria: July 17, 2025
• First Posted (Actual): July 25, 2025

Study Record Updates

• Last Update Posted (Actual): July 31, 2025
• Last Update Submitted That Met QC Criteria: July 30, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Antineoplastic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Micronutrients; Topoisomerase I Inhibitors; Topoisomerase Inhibitors; Protective Agents; Antidotes; Vitamin B Complex; Vitamins; Oxaliplatin; Irinotecan; Leucovorin
• Other Study ID Numbers: 25-OBU-HN-GC-II-012

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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