Phase I Trial of Intraperitoneal Bevacizumab in Refractory Malignant Ascites

Exclusion Criteria

• •1. systematic anti-cancer therapy, including chemotherapy (intraperitoneal chemotherapy), radiation therapy, immunotherapy, biological or hormone therapy performed within 2 weeks;
• •2. tyrosine kinase inhibitors or monoclonal antibodies of anti-vascular endothelial growth factor (VEGF) performed within 4 weeks;
• •3. Laboratory tests:Absolute neutrophil count\<1.0x109/L,Platelet count\<75x 109/L,Hemoglobin\<8g/dl,PT-INR≥1.5 times upper limit of normal (ULN);Bilirubin≥2 x ULN,AST and ALT≥2.5 times ULN(no liver metastasis),≥5 times ULN(with liver metastasis)Creatinine≥1.5 times ULN or calculated creatinine clearance, using the Cockcroft-Gault formula,\<40 mL/min;
• •4. uncontrolled hypertension:systolic pressure ≥160 mmHg,or diastolic pressure≥100mmHg
• •5. Known history of severe heart disease,uncontrolled or symptomatic angina, congestive heart failure,clinically significant arrhythmias,myocardial infarction within six months;
• •6. active (severe or uncontrolled) bleeding (hemorrhage within 3 months\> 30 ml), hemoptysis (fresh blood, 4 weeks\> 5 ml), bloody ascites
• •7. thrombosis, tumor thrombus events (including arterial/venous thrombosis, tumor thrombosis, pulmonary embolism, transient ischemic attack)within 12 months;
• •8. Portal hypertensive disease or severe liver disease, including various types of cirrhosis, obstructive jaundice;
• •9. concurrent gastrointestinal obstruction, peptic ulcer, Crohn's disease, ulcerative colitis and other gastrointestinal diseases according to investigators' determination that may cause gastrointestinal bleeding or perforation;
• •10. concurrent severe respiratory disease, or chronic therapy with oxygen or corticosteroids, such as chronic obstructive pulmonary disease, interstitial lung disease, etc.
• •11. Unresolved or unstable, serious toxicity from prior cancer treatment (any toxicities greater than grade 2 or not recovered from surgery;
• •12. Symptomatic brain metastasis;
• •13. Uncontrolled systemic disease,such as infection,unstable diabetes mellitus,etc;
• •14. Active infection of HIV、HBV、HCV；
• •15. Major surgery within 4 weeks of start of study treatment, without complete recovery.
• •16. Pregnant or lactating women.Negative serum pregnancy test (For women of childbearing potential);Fertile patients must use effective contraception.
• •17. Dementia, altered mental status, or any psychiatric condition that would prevent the understanding or rendering of ICF;
• •18. Received any investigational drug treatment within 4 weeks of start of study treatment.