s1+ paclitaxel (iv&ip) + bevacizumab (ip) versus s1+oxaliplatin as first-line treatment in gastric cancer with malignant ascites

Conditions: Metastatic Gastric Adenocarcinoma

Summary: the purpose of this study is to compare the efficacy of s1 plus paclitaxel (intravenous injection \& intraperitoneal injection) plus bevacizumab (intraperitoneal injection) vs. s1 plus oxaliplatin intravenous injection as first-line treatment in gastric or gastroesophageal junctional adenocarcinoma with malignant ascites.

this is a prospective, open-label, multicenter clinical trial, to compare the efficacy of s1 plus paclitaxel (intravenous injection \& intraperitoneal injection) plus bevacizumab (intraperitoneal injection) versus s1 plus oxaliplatin intravenous injection as first-line treatment in gastric or gastroesophageal junctional adenocarcinoma with malignant ascites. a total of 66 patients who are diagnosed with gastric or gastroesophageal junctional adenocarcinoma will be allocated to receive either s1 orally administration plus paclitaxel intravenous injection \& intraperitoneal injection plus bevacizumab intraperitoneal injection, or to receive s1 orally administration plus oxaliplatin intravenous injection. the primary end point is ascites response rate at 6 weeks. the secondary end points include the median overall survival (os), progression-free survival (pfs), time to treatment failure (ttf), objective response rate (orr), puncture free survival, volume of drainage, the quality of life (qol) and safety.

Eligibility criteria:
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.

Keywords: gastric carcinoma malignant ascites intraperitoneal chemotherapy bevacizumab