A randomized phase II study of systemic chemotherapy with and without trastuzumab followed by surgery in HER2 positive advanced gastric or esophagogastric junction adenocarcinoma with extensive lymph node metastasis (JCOG1301C: Trigger Study)

INTERVENTION: Preoperative chemotherapy with S‐1 plus cisplatin followed by D2 or D2+No.16 gastrectomy and postoperative chemotherapy with S‐1 treatment for a year. Preoperative chemotherapy with trastuzumab combined with S‐1 plus cisplatin followed by D2 or D2+No.16 gastrectomy and postoperative chemotherapy with S‐1 treatment for a year. CONDITION: HER2 positive gastric or esophagogastric junction adenocarcinoma with extensive lymph node metastasis. PRIMARY OUTCOME: Overall survival SECONDARY OUTCOME: progression‐free survival, response rate of preoperative chemotherapy, proportion of patients with R0 resection, proportion of patients who complete the preoperative chemotherapy and surgery, proportion of patients who complete the protocol treatment, pathological response rate, proportion of adverse events and proportion of severe adverse events. INCLUSION CRITERIA: 1) Histologically proven primary gastric adenocarcinoma. 2) HER2 positive (IHC 3+ or IHC 2+ and ISH +). 3) Contrast‐enhanced abdominal computed tomography (CT) revealed at least one of the following: i. Para‐aortic lymph node enlargement >=1.0 cm in major axis between the upper margin of the celiac artery and the upper border of the inferior mesenteric artery (No. 16a2/ 16b1) ii. Bulky lymph nodes (>=3 cm 1or>=1.5 cm 2 in major axis) along the celiac, splenic, common or proper hepatic arteries, or the superior mesenteric vein iii. T2‐T4 disease with enlarged regional lymph node (>= 1.5 cm in minor axis) 4) Contrast‐enhanced thoracic/abdominal/pelvic CT revealed no metastatic lesion other than the lymph node metastasis. 5) The macroscopic tumor type is neither Borrmann type 4 (linitis plastica) nor large (8 cm or more) type 3 6) No esophageal invasion or an invasion of 3 cm or less 7) No gastric stump cancer 8) No prior ch