Background: Approximately 10-20% of patients with gastric cancer (GCa) have HER-2 positive tumors. The addition of T to cisplatin/fluoropyrimidine-based CT improved survival in metastatic HER-2 positive GCa. When P was added to T and CT, a significant increase in the histopathological complete response rate was observed in HER-2 positive breast cancer. This study aims to investigate the added value of combining both HER-2 targeting drugs with perioperative CT for GCa and gastroesophageal-junction cancer (GEJCa). Methods: This is a randomized, open-label phase II trial. Biopsies from patients with resectable GCa or GEJCa (UICC tumor stage Ib-III) will be centrally screened for HER-2. Over a 4-year accrual period, 225 patients with HER-2 positive cancers will be centrally randomized (1:2:2 ratio) across 52 centers in 10 European and 3 non-European countries in one of the three arms: - Control arm: Cisplatin (80 mg/m2 every 3 weeks) and capecitabine (1000 mg/m2 twice daily every 2 out of 3 weeks), or 5-FU (800 mg/m2/day for 5 days every 3 weeks) for 3 cycles before and after surgery - Experimental arm 1: CT plus T (8 mg/kg loading dose, followed by 6mg/kg every 3 weeks) - Experimental arm 2: CT plus T plus P (840mg every 3 weeks) T and/or P will be administered on day 1 of every CT cycle and continued afterwards for a total of 17 cycles. Stratification will be done by histological subtype (intestinal/non-intestinal); region (Korea vs Europe); location (GEJCa vs non-GEJCa) and HER-2 (immunohistochemistry 3+ vs IHC 2+/FISH+). The primary objective is to detect an increase in the pathological response rate (RR, < 10% residual tumor cells) as determined by central review, from 15% to 30% with addition of T or T and P. The RR in each experimental arm will be tested versus 15% with a one-sided type I error of 5%. If both tests are positive, the experimental arm with the higher RR will be recommended if the difference exceeds 5%. The recruitment has started in September 2015. Clinical trial information: NCT02205047