Background: In Japan, while post-operative adjuvant chemotherapy with S-1 or capecitabine plus oxaliplatin is standard care for pStage II/III gastric cancer after curative resection with D2 lymph node dissection, the clinical outcomes of pStage III patients are not satisfactory. In Europe, neoadjuvant chemotherapy (NAC) followed by gastrectomy is standard. The Japan Clinical Oncology Group (JCOG) has conducted several phase II trials of NAC, and deemed NAC as one of the most promising treatment strategies for gastric cancer with lymph node metastasis (Stage III). However, no established criteria exists for diagnosis of lymph node metastasis. JCOG1302A which was a cross-sectional study evaluating the accuracy of preoperative staging by imaging, showed that cT3-4N1-3M0 (positive lymph node was defined as that with a long axis diameter ≥ 10 mm or short axis diameter ≥ 8 mm) included just 6.5% overdiagnosed pStage I patients and accounted for 52.6% of all pStage III patients. Methods: JCOG1509 (UMIN000024065) is designed as a randomized phase III study to confirm the survival superiority of addition of NAC to standard treatment for patients with cT3-4N1-3M0 gastric cancer. In the standard arm, a gastrectomy with D2 lymphadenectomy is performed followed by adjuvant chemotherapy with oral S-1 for 1 year. In the experimental arm, combination of an infusion of oxaliplatin (130 mg/m²/day, day 1) and oral S-1 (80 mg/m²/day, days 1–14) is repeated every 3 weeks for 3 courses before gastrectomy, followed by surgery and adjuvant chemotherapy with S-1 for 1 year. The primary endpoint is overall survival. The planned sample size is 470 in total with a 1-sided alpha of 5%, a power of 80%, expecting a 10% increase in the 5-year OS (60% vs 70%). Patients will be enrolled from 58 Japanese institutions over 3.5 years. The study was activated in September 2016 and, as of January 2017, 18 patients were enrolled for the study. Clinical trial information: UMIN000024065.