Ramucirumab (Cyramza), Nal-IRI (ONIVYDE) and Trifluridine/Tipiracil (Lonsurf) in Second Line Metastatic Gastric Cancer .

Inclusion Criteria: histologically or cytologically confirmed metastatic gastric adenocarcinoma patients have received only first line of systemic therapy, including recurrence during adjuvant therapy or within 6 months after the completion of adjuvant treatment. ECOG(Eastern Cooperative Oncology Group) performance status 0 or 1 patients with HER2/neu-positive tumor must be exposure to Herceptin treatment at least one measurable disease according to the RECIST version 1.1; patients are aged 20 to 80 years; patients have a life expectancy ≥ 3 months; patients have adequate renal function with defined as serum creatinine ≤ 1.5 times the upper limit of normal (ULN) or Ccr ≥ 40 mL/min; patients with adequate hepatic function as defined by a total bilirubin ≤1.5 times the ULN, and aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 times the ULN or 5 times the ULN in the setting of liver metastases. patients have adequate bone marrow function, defined as an absolute neutrophil count ≥ 1500/mm3, hemoglobin ≥9 g/dL, and platelet count ≥ 100,000/mm3 (transfusion or G-CSF support before enrollment is allowed) patients have International Normalized Ratio (INR) ≤1.5 and a partial thromboplastin time (PTT) (PTT/aPTT) < 1.5 x ULN; patients' urinary protein is ≤1+ on dipstick or routine urinalysis or a 24-hour urine collection for protein must demonstrate <1000 mg of protein if urine dipstick or routine analysis is ≥ 2+; patients with childbearing potential shall have effective contraception for both the patient and his or her partner during the study; female patients of childbearing potential must have a negative serum pregnancy test within 7 days prior to first dose of protocol therapy; the ability to understand and willingness and to sign a written informed consent document. Exclusion Criteria: patient can't take oral drugs; known hypersensitivity to irinotecan, fluoropyrimidine, or ramucirumab; receipt of surgery within the past 4 weeks before study enrollment; ≥ grade 2 diarrhea and ascites concurrent severe infection with intravenous systemic antibiotics treatment; patients have experienced any arterial thromboembolic events, including but not limited to myocardial infarction, transient ischemic attack, cerebrovascular accident, or unstable angina, within 6 months prior to first dose of protocol therapy; patients have a prior history of GI perforation/fistula (within 6 months of first dose of protocol therapy) or risk factors for perforation; patients have: cirrhosis at a level of Child-Pugh B (or worse) or cirrhosis (any degree) and a history of hepatic encephalopathy or clinically meaningful ascites resulting from cirrhosis. Clinically meaningful ascites is defined as ascites from cirrhosis requiring diuretics or paracentesis; patients have a serious or nonhealing wound, ulcer, or bone fracture within 28 days prior to first dose of protocol therapy; patients have undergone major surgery within 28 days prior to first dose of protocol therapy, or minor surgery/subcutaneous venous access device placement within 7 days prior to the first dose of protocol therapy. Patients have elective or planned major surgery to be performed during the course of the clinical trial; patients have uncontrolled or poorly-controlled hypertension (>160 mmHg systolic or > 100 mmHg diastolic for >4 weeks) despite standard medical management; patients have experienced any grade 3-4 GI bleeding within 3 months prior to first dose of protocol therapy; patients have a history of deep vein thrombosis (DVT), pulmonary embolism (PE), or any other significant thromboembolism (venous port or catheter thrombosis or superficial venous thrombosis are not considered "significant") during the 3 months prior to first dose of protocol therapy; patients are receiving chronic antiplatelet therapy, including dipyridamole or clopidogrel, or similar agents. Once-daily aspirin use (maximum dose 325 mg/day) is permitted; previously received prior nal-IRI (ONIVYDE®) or TAS-102 (LONSURF®) or ramucirumab therapy another previous malignancy diagnosed within the past 5 years except for nonmelanoma skin cancer or stage I cervical cancer; pregnant or breastfeeding women.