['gastric adenocarcinoma', 'gastroesophageal junction adenocarcinoma']
['ramucirumab', 'paclitaxel']

        Inclusion Criteria:

          1. The patient has histologically or cytologically confirmed gastric carcinoma, including
             gastric adenocarcinoma or GEJ adenocarcinoma. (Patients with adenocarcinoma of the
             distal esophagus are eligible if the primary tumor involves the GEJ.)

          2. The patient has metastatic disease or locally recurrent, unresectable disease.

          3. The patient has measureable or evaluable disease as determined by standard computed
             tomography (CT) or magnetic resonance imaging (MRI) imaging. Examples of evaluable,
             nonmeasurable disease include gastric, peritoneal, or mesenteric thickening in areas
             of known disease, or peritoneal nodules that are too small to be considered measurable
             by Response Evaluation Criteria in Solid Tumors (RECIST version 1.1) (48).

          4. The patient has experienced disease progression during treatment or within 4 months
             after the last dose of first-line therapy for metastatic disease.

               -  Acceptable prior chemotherapy regimens for this protocol are combination
                  chemotherapy regimens that include platinum and/or fluoropyrimidine components
                  (acceptable prior platinum agents are cisplatin, carboplatin, or oxaliplatin;
                  acceptable prior fluoropyrimidine agents are 5-FU, capecitabine, or S-1).
                  Regimens including a third agent, such as an anthracycline or a taxane, are
                  acceptable provided a fluoropyrimidine and/or a platinum were used.

               -  Recurrence during or within 6 months of completion of adjuvant chemotherapy
                  (capecitabine, 5-FU, or TS-1) will be considered as first-line chemotherapy.

          5. The patient's disease is not amenable to potentially curative resection.

          6. The patient is ≥18 years of age.

          7. The patient has resolution to Grade ≤1 (or to Grade ≤2 in the case of neuropathy) by
             the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-
             CTCAE), Version 4.03, of all clinically significant toxic effects of prior
             chemotherapy, surgery, radiotherapy, or hormonal therapy (with the exception of
             alopecia).

          8. The patient has an Eastern Cooperative Oncology Group performance status (ECOG PS)
             score of 0 or 1.

          9. The patient has adequate hepatic function as defined by a total bilirubin ≤1.5 mg/dL
             (25.65 µmol/L), and aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0
             times the upper limit of normal (ULN; or 5.0 times the ULN in the setting of liver
             metastases).

         10. The patient does not 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.

         11. The patient has adequate renal function as defined by a serum creatinine ≤1.5 times
             the ULN, or creatinine clearance (measured via 24-hour urine collection) ≥40 mL/minute
             (that is, if serum creatinine is >1.5 times the ULN, a 24-hour urine collection to
             calculate creatinine clearance must be performed).

         12. The patient's urinary protein is ≤1+ on dipstick or routine urinalysis (UA; if urine
             dipstick or routine analysis is ≥2+, a 24-hour urine collection for protein must
             demonstrate <1000 mg of protein in 24 hours to allow participation in this protocol).

         13. The patient has adequate hematologic function, as evidenced by an absolute neutrophil
             count (ANC) ≥1000/µL, hemoglobin ≥9 g/dL (5.58 mmol/L), and platelets ≥100,000/µL.

         14. The patient must have adequate coagulation function as defined by international
             normalized ratio (INR) ≤1.5 and a partial thromboplastin time (PTT) ≤5 seconds above
             the ULN (unless receiving anticoagulation therapy). Patients on full-dose
             anticoagulation must be on a stable dose (minimum duration 14 days) of oral
             anticoagulant or low molecular weight heparin. If receiving warfarin, the patient must
             have an INR ≤3.0 and no active bleeding (that is, no bleeding within 14 days prior to
             first dose of protocol therapy) or pathological condition present that carries a high
             risk of bleeding (for example, tumor involving major vessels or known varices).
             Patients on anticoagulation therapy with unresected primary tumors or local tumor
             recurrence following resection are not eligible.

         15. If the patient has received prior anthracycline therapy as part of his or her
             first-line regimen, the patient is able to engage in ordinary physical activity
             without significant fatigue or dyspnea (equivalent to New York Heart Association Class
             I function) (49).

         16. Because the teratogenicity of ramucirumab is not known, the patient, if sexually
             active, must be postmenopausal, surgically sterile, or using effective contraception
             (hormonal or barrier methods).

         17. Female patients of childbearing potential must have a negative serum pregnancy test
             within 7 days prior to enrollment.

         18. The patient is able to provide informed written consent.

         19. Feasible biopsy site

        Exclusion Criteria:

          1. The patient has documented and/or symptomatic brain or leptomeningeal metastases.

          2. The patient has experienced any Grade 3 to 4 GI bleeding within 3 months prior to
             enrollment.

          3. The patient has 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 enrollment.

          4. The patient has an ongoing or active infection, symptomatic congestive heart failure,
             unstable angina pectoris, symptomatic or poorly controlled cardiac arrhythmia,
             uncontrolled thrombotic or hemorrhagic disorder, or any other serious uncontrolled
             medical disorders in the opinion of the treating physician.

          5. The patient has ongoing or active psychiatric illness or social situation that would
             limit compliance with treatment.

          6. The patient has uncontrolled or poorly controlled hypertension (>160 mmHg systolic or
             >100 mmHg diastolic for >4 weeks) despite standard medical management.

          7. The patient has a serious or nonhealing wound, ulcer, or bone fracture within 28 days
             prior to enrollment.

          8. The patient has received chemotherapy, radiotherapy, immunotherapy, or targeted
             therapy for gastric cancer within 2 weeks prior to enrollment.

          9. The patient has received any investigational therapy within 30 days prior to
             enrollment.

         10. The patient has undergone major surgery within 28 days prior to enrollment, or
             subcutaneous venous access device placement within 7 days prior to enrollment.

         11. The patient has received prior therapy with an agent that directly inhibits VEGF
             (including bevacizumab), or VEGF Receptor 2 activity, or any antiangiogenic agent.

         12. The patient is receiving chronic antiplatelet therapy, including aspirin, nonsteroidal
             anti- inflammatory drugs (NSAIDs; including ibuprofen, naproxen, and others),
             dipyridamole or clopidogrel, or similar agents. Once-daily aspirin use (maximum dose
             325 mg/day) is permitted.

         13. The patient has elective or planned major surgery to be performed during the course of
             the clinical trial.

         14. The patient has a known allergy to any of the treatment components.

         15. The patient is pregnant or breastfeeding.

         16. The patient is known to be positive for infection with the human immunodeficiency
             virus (HIV).

         17. The patient has known alcohol or drug dependency.

         18. The patient has a concurrent active malignancy other than adequately treated
             nonmelanomatous skin cancer, other noninvasive carcinoma, or in situ neoplasm.

         19. The patient has a known hypersensitivity to ramucirumab or any of the excipients.

         20. The patient may not have received more than 1 prior therapy in the metastatic setting.
      