S1+ Paclitaxel (IV&IP) + Bevacizumab (IP) Versus S1+Oxaliplatin as First-line Treatment in Gastric Cancer With Malignant Ascites

Inclusion Criteria:

* 18 years ≥ Age≤ 70 years, male or female
* Pathologically confirmed adenocarcinoma of the gastric or gastro-oesophageal junction with inoperable locally advanced or recurrent and/or metastatic disease; with medium amount of malignant ascites which can be catheterized.
* Diagnostic criteria for malignant ascites (meet any of the following criteria): ascites cytology positive; or imaging or pathological confirmed peritoneal metastases.
* No prior anti-tumor treatment to the metastatic disease; an interval of at least 6 months from the last adjuvant chemotherapy.
* Eastern Cooperative Oncology Group (ECOG) performance status( PS) score 0-1.
* Normal major organ function, and laboratory tests must meet the following criteria: hemoglobin (HGB) ≥ 90 g/L, neutrophil count ≥ 1.5×109/L, platelet count ≥ 100×109/L, total bilirubin (TBil) ≤ 1.5 upper normal limitation (UNL), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 UNL, serum creatinine (Cr) ≤ 1 UNL; creatinine clearance rate (CCr) ≥ 60 ml/min (calculated using the Cockcroft-Gault equation).
* International Normalized Ratio (INR) ≤ 1.5 and partial prothrombin time (PPT) or activated partial thromboplastin time (APTT) ≤ 1.5 UNL within 7 days before enrollment.
* Life expectancy of at least 12 weeks
* Signed informed consent (ICF)
* For women of child bearing potential, a negative serum or urine pregnancy test result should be obtained with 7 days before enrollment; Women of childbearing potential and men must agree to use adequate contraception before entering the program until at least 8 weeks after the last study drug administration.

Exclusion Criteria:

* Known hypersensitivity or allergic to any of the study drugs, study drug classes, or excipients in the formulation.
* Subject received chemotherapy to the metastatic disease (except adjuvant/neoadjuvant chemotherapy administered 24 weeks before enrollment)
* Subject with other malignancies, except for non-melanoma skin cancer or in-situ cervical carcinoma under adequate treatment, or other treated malignancies without evidence of recurrent for 5 years.
* Anti-tumor cytotoxic drug therapy within 14 days prior to enrollment（longer washout time interval might needed depends on drug characteristics）
* Uncontrolled hypertension which cannot be reduced to normal range by antihypertensive agents \[Systolic Blood Pressure(SBP) \>140 mmHg, diastolic blood pressure (DBP) \> 90 mmHg\], coronary artery disease \> grade 1, arrhythmia \> grade 1 \[including corrected QT(QTc) interval prolongation: QTc\>450 ms for male，QTc\>470 ms for female\], grade 1 heart failure.
* Proteinuria ≥ ++，or persistent proteinuria \> 1.0 g/24 hours
* Presence of any toxicity ≥ grade 1 according to NCI-CTCAE except for alopecia.
* Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks, cerebral hemorrhage、cerebral infarction), deep vein thrombosis and pulmonary embolism within 12 months before enrollment.
* Bowel obstruction within 6 weeks before enrollment.
* Surgical treatment was performed within 6 weeks before enrollment. Subject should recover from any major surgery.
* Serious uncontrolled systemic illness or medical condition or uncontrolled infections, including but not limited to: uncontrollable ventricular arrhythmias, history of documented myocardial infarction within 3 months, uncontrollable epileptic dementia, unstable spinal compression, superior vena cava syndrome, extensive bilateral interstitial pulmonary disease by high-resolution computed tomography (HRCT), or any neurological or mental abnormalities which affect compliance.
* Human immunodeficiency virus (HIV) positive
* Pregnancy or lactation women
* Cannot be orally administered medication
* Subject with a tendency for gastrointestinal hemorrhage. Including: Black stool or hematemesis within 2 months; For subjects positive in occult test with unresected primary lesion, if the principle investigator in each center considers with possibility of gastrointestinal hemorrhage, the subject could not be enrolled.
* Subject with malignant pleural effusion need medical intervention.
* A history or evidence of hereditary hemorrhagic constitution or coagulation disorder that increases the risk of bleeding
* Subjects with central nerve system metastases
* Have been enrolled in other clinical trial with investigational drug treatment within the 4 weeks of start of study treatment
* For subject with bone metastases, palliative radiotherapy was given 4 weeks before enrollment (radiation field \>5%).
* Any other disease or condition that the investigator considers not suitable for participating in this clinical trial.