A Clinical Study Comparing Anti-HER2 Therapy Combined With Chemotherapy to Chemotherapy Alone as Adjuvant Therapy Following Surgery for Stage IB-II Gastric Cancer With High HER2 Expression.

A Randomized, Controlled, Open-Label, Multicenter Clinical Trial Comparing Anti-HER2 Therapy Combined With Chemotherapy to Chemotherapy Alone as Adjuvant Therapy Following Surgery for Stage IB-II Gastric Cancer With High HER2 Expression

This study employs a multicenter randomized controlled trial design, led by the First Affiliated Hospital of Air Force Medical University (Xijing Hospital) in collaboration with 10 other domestic medical institutions, for a total of 11 research centers. The study plans to enroll a total of 120 HER-2-positive gastric cancer patients, including those who drop out, and randomize them into two groups in a 1:1 ratio; The control group received treatment based on gastric cancer stage: Stage IB patients were treated with tegafur monotherapy (40-60 mg orally twice daily based on body surface area, on days 1-14, with a 21-day cycle, for a total of 6 cycles); Stage II patients will receive chemotherapy using either the SOX or XELOX regimen, both of which involve an intravenous infusion of oxaliplatin 130 mg/m² on Day 1, combined with the corresponding oral medications for 14 consecutive days, with a 21-day cycle, for a total of 6 treatment cycles; In addition to the control group's original chemotherapy regimen, the experimental group concurrently received Fuhong Hanlin trastuzumab (National Drug Approval No. S20200019, 150 mg/vial) in addition to the control group's original chemotherapy regimen. The first dose was an 8 mg/kg intravenous loading dose, followed by a maintenance dose of 6 mg/kg, administered concurrently starting on the first day of the first chemotherapy cycle, with each cycle lasting 21 days, and the treatment course consisting of 6 cycles.

Inclusion Criteria:

• Age ≥ 18 years; Open to all genders;
• Patients with a definitive histopathological diagnosis of gastric adenocarcinoma or gastroesophageal junction adenocarcinoma, and an ECOG score ≤ 2;
• Gastric cancer or gastroesophageal junction cancer with TNM stage IB-II;
• HER-2-positive (IHC 3+ or IHC 2+ with amplification confirmed by FISH/SISH/CISH);
• Tumor resection has been completed, and adjuvant therapy is planned postoperatively;
• Adequate organ function; participants must meet the following laboratory criteria:
• Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L, without the use of granulocyte colony-stimulating factor (G-CSF) within the past 14 days;
• Platelet count ≥ 100 × 10⁹/L, without a blood transfusion within the past 14 days;
• Hemoglobin > 9 g/dL, without a blood transfusion or the use of erythropoietin within the past 14 days;
• Total bilirubin ≤ 1.5 × upper limit of normal (ULN);
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN;
• Serum creatinine ≤ 1.5 × ULN and creatinine clearance (calculated using the Cockcroft-Gault formula) ≥ 60 mL/min;
• Normal coagulation function, defined as an International Normalized Ratio (INR) or prothrombin time (PT) ≤ 1.5 times the ULN;
• Normal thyroid function, defined as thyroid-stimulating hormone (TSH) within the normal range. If baseline TSH is outside the normal range, subjects may still be enrolled provided that total T3 (or FT3) and FT4 are within the normal range;
• Cardiac enzyme levels are within the normal range (participants with isolated laboratory abnormalities deemed clinically insignificant by the investigator's comprehensive assessment may also be enrolled);
• Voluntary participation in the study and signing of an informed consent form prior to study initiation.

Exclusion Criteria:

• Other malignant tumors of the stomach;
• Received, prior to screening, or is scheduled to receive during the trial any anticancer therapy other than the chemotherapy regimen specified in the protocol (e.g., radiation therapy, targeted therapy, immunotherapy);
• Has or has had a malignant tumor in any other part of the body (except for adequately treated cervical carcinoma in situ, basal cell carcinoma of the skin, or other tumors that have been surgically cured and have not recurred for at least 5 years);
• Presence of any severe or uncontrolled systemic disease, such as:
• Unstable angina, congestive heart failure, or chronic heart failure classified as New York Heart Association (NYHA) Class ≥ 2;
• Significant and symptomatic, difficult-to-control abnormalities in rhythm, conduction, or morphology on a resting electrocardiogram, such as complete left bundle branch block, second-degree or higher heart block, ventricular arrhythmias, or atrial fibrillation;
• Any arterial thrombosis, embolism, or ischemia occurring within 6 months prior to enrollment, such as myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack;
• Poorly controlled blood pressure (systolic blood pressure > 150 mmHg, diastolic blood pressure > 100 mmHg);
• A history of non-infectious pneumonia requiring glucocorticoid therapy within 1 year prior to the first dose, or current clinically active interstitial lung disease;
• Active pulmonary tuberculosis;
• Active or uncontrolled infection requiring systemic treatment;
• Clinically active diverticulitis, intra-abdominal abscess, or gastrointestinal obstruction;
• Liver disease, such as cirrhosis, decompensated liver disease, or acute or chronic active hepatitis;
• Poorly controlled diabetes (fasting blood glucose (FBG) > 10 mmol/L);
• Patients with urine protein ≥++ on urinalysis and confirmed 24-hour urine protein quantification > 1.0 g;
• Patients with psychiatric disorders who are unable to comply with treatment;
• Patients currently participating in other clinical trials or who have participated in other clinical trials within the past 3 months;
• Patients with known allergies to the medications used in this study;
• Patients deemed unsuitable for participation in this clinical trial by the investigator.