Background: Docetaxel plus cisplatin and fluorouracil (TCF) improved time to progression and survival compared with CF in advanced gastric cancer (GC). We conducted a randomized phase II study of T plus oxaliplatin (E) with or without fluorouracil (F) or capecitabine (X) in advanced GC. Methods: The GATE study is a multinational, randomized, 3-parallel-arm, stratified study. Optimal doses for all regimens were determined in a pilot phase. Patients ≥18 of age, with a KPS >70 and histologically proven metastatic or locally advanced GC not treated with chemotherapy for advanced GC were randomized to TEF (T 50 mg/m² followed by E 85 mg/m² simultaneously with folinic acid 400 mg/m² followed by F 2400 mg/m² as a 46-hr continuous infusion on Day 1, q2w), TE (T 75 mg/m² followed by E 130 mg/m² on Day 1 q3w), and TEX (T 50 mg/m² followed by E 100 mg/m² Day 1, q3w and X 625 mg/m² BID continuously). The primary objective was time to progression (TTP) in the evaluable population; secondary objectives included response rate (RR), overall survival (OS), and safety. Results: 254 patients were randomized, and 248 received treatment (n=88 TEF, n=78 TE, n=82 TEX). Baseline characteristics were balanced among treatment groups. Most common Gr 3–4 adverse events across treatment arms were fatigue (20.6%), sensory neuropathy (13.7%), diarrhea (12.5%), and anorexia (6.0%); the febrile neutropenia rate was 8.1%. The proportion of deaths due to adverse events were 3.4% with TEF vs. 5.1% with TE and 13.4% with TEX. Conclusions: In patients with advanced GC, treatment with TEF was associated with improved TTP, RR and OS, with a better safety profile compared with TE and TEX.