RESONANCE-II trial is a prospective, multicenter, randomized, controlled phase III study which will enroll 524 patients in total. Patients with eligibility will be registered, pre-enrolled and receive three cycles of SOX. Then, tumor response evaluation will be carried out. Those who achieve stable disease or progressive disease will be excluded. Patients achieving complete response or partial response will be enrolled and assigned into either group A for another three cycles of SOX (six cycles in total) followed by D2 surgery and group B for D2 surgery (three cycles in total). The primary endpoint is the rate of pathological complete response and the secondary endpoints are R0 resection rate, three-year disease-free survival, five-year overall survival and safety.

RESONANCE-II trial is a prospective, multicenter, randomized, controlled phase III study which was designed to evaluate the efficacy and safety of different cycles of SOX as neoadjuvant chemotherapy for patients with locally advanced gastric cancer. All patients with eligibility will be registered, pre-enrolled and receive three cycles of SOX. Then, tumor response evaluation will be carried out according to the Response Evaluation Criteria for Solid Tumors (RECIST) 1.1. Those who achieve stable disease (SD) or progressive disease (PD)will be excluded. Patients achieving complete response (CR) or partial response (PR) will be enrolled and assigned into either group A (six cycles of neoadjuvant chemotherapy with SOX) for another three cycles of SOX followed by D2 surgery and group B (three cycles of neoadjuvant chemotherapy with SOX) for D2 surgery. The primary endpoint is the rate of pathological complete response (pCR%) and the secondary endpoints are R0 resection rate, three-year disease-free survival (3-y DFS), five-year overall survival (5-y OS) and safety.

Inclusion Criteria:

1. Non-bedridden, aged 18 to 70 years old;
2. Eastern Cooperative Oncology Group (ECOG) score is 0 to 1;
3. Histologically confirmed gastric adenocarcinoma;
4. Stage III (American Joint Committee on Cancer (AJCC) TNM staging system 8th edition) gastric cancer confirmed by enhanced computer tomography (enhanced CT) and laparoscopic exploration (endoscopic ultrasonography (EUS) and magnetic resonance imaging (MRI) if necessary);
5. The research center and the surgeon have the ability to complete standard D2 radical gastrectomy, and the gastrectomy can be tolerated by the patient;
6. Laboratory test criteria: peripheral blood hemoglobin (Hb) ≥ 90 g/L, neutrophil absolute count ≥ 3×109 /L, platelet count (PLT) ≥ 100×109 /L, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 times the upper limit of normal (ULN), total bilirubin ≤ 1.5×ULN, serum creatinine (SCr) ≤ 1.5×ULN, and serum albumin (ALB) ≥ 30 g/L;
7. Patients with heart disease, the echocardiogram showed that the left ventricular ejection fraction ≥ 50%, the electrocardiogram (ECG) is basically normal within 4 weeks before operation and without no obvious symptoms are acceptable;
8. There is no serious underlying disease that could lead to an expected life expectancy < 5 years;
9. Willing to sign the inform consent for participation and publication of results.

Exclusion Criteria:

1. Pregnant or lactating women;
2. Positive pregnancy test for women in childbearing age. Menopausal women without menstruation for at least 12 months can be regarded as women with no possibility of getting pregnant;
3. Refuse to birth control during the study;
4. Received any chemotherapy, radiotherapy or immunotherapy before;
5. History of other malignant diseases in the last five years (except for cervical carcinoma in situ);
6. History of uncontrolled central nervous system diseases, which could influence the compliance;
7. History of severe liver diseases, renal diseases or respiratory diseases; Uncontrolled diabetes and hypertension; Clinically severe heart disease, such as congestive heart failure, symptomatic coronary heart disease, uncontrolled arrhythmia, or a history of myocardial infarction in the last six months;
8. History of dysphagia, complete or partial gastrointestinal obstruction, active gastrointestinal bleeding and gastrointestinal perforation;
9. On steroid treatment after organ transplant;
10. With uncontrolled severe infections;
11. Known dihydropyrimidine dehydrogenase deficiency (DPD);
12. Anaphylaxis to any research drug ingredient;
13. Known peripheral neuropathy (> NCI-CTC AE 1). Patients with only disappearance of deep tendon reflex need not to be excluded.