Background: Paclitaxel and ramucirumab combination therapy had become a standard regimen in the second-line treatment of advanced gastric cancer, since RAINBOW trial showed paclitaxel and ramucirumab combination therapy increased overall survival compared with paclitaxel monotherapy. However, the incidence of neuropathy in paclitaxel and ramucirumab combination therapy has been reported 70.6% and 38.3% in Japanese and western patients, and the toxicity sometimes disturbs treatment continuation. Whereas docetaxel monotherapy used to be one of standard second-line treatment of advanced gastric cancer as well as paclitaxel monotherapy because the phase III trial, COUGAR-2 showed clinical benefit of docetaxel monotherapy. In addition, the combination therapy of docetaxel and ramucirumab was reported to cause neuropathy at an incidence of 21.3% in patients with lung cancer. Based on these results, we hypothesized that the combination therapy of docetaxel and ramucirumab for patients with gastric cancer could be as effective as the paclitaxel and ramucirumab combination therapy and could reduce the incidence of neuropathy. Therefore, we planned to develop new combination chemotherapy with docetaxel and ramucirumab for advanced gastric cancer. Methods: To evaluate efficacy and safety of docetaxel and ramucirumab combination therapy, HGCSG1903 study started as a multicenter, non-randomized, single arm, prospective, phase II study in November 2020. The patients with metastatic gastric adenocarcinoma that were refractory or intolerant to initial chemotherapy are eligible. Docetaxel and ramucirumab combination therapy is administered as follows; an intravenous infusion of docetaxel at 60 mg/m² on day 1, an intravenous infusion of ramucirumab at 8 mg/kg on day 1 and day 15 of each 4-week cycle is performed. The therapy is repeated until disease progression, unacceptable toxicity, or patient refusal. The primary endpoint is response rate, and the secondary endpoints are overall survival, progression-free survival, safety, and dose intensity for each drug. The response rate is calculated based on the RECIST version 1.1 criteria. Adverse events are evaluated using the CTCAE v5.0 criteria. A hypothesis test of binary probability was performed, with condition that threshold of response rate was set to 10.7% of docetaxel monotherapy in phase III trial and the expected response rate was set to 27.9% of paclitaxel and ramucirumab combination therapy in RAINBOW trial. A minimum number of cases that achieved a detection power of 80% at a one-sided significance level of 5% was calculated to be 32 cases. In anticipation of dropouts, the total number of registration cases was set to 35. Sixteen institutions are participated, and the registration period is 2 years. This study is registered with Japan Registry of Clinical Trials (jRCTs011200010). Clinical trial information: jRCTs011200010.