A Phase III Study of 2nd-line XELIRI ± Bevacizumab vs. FOLFIRI ± Bevacizumab in mCRC

Exclusion Criteria

• •1. History of other malignancy with a disease-free interval \<5 years (other than curatively treated cutaneous basal cell carcinoma, curatively treated carcinoma in situ of the cervix, and gastroenterological cancer confirmed to be cured by endoscopic mucosal resection)
• •2. With massive pleural effusion or ascites requiring intervention
• •3. Radiological evidence of brain tumor or brain metastases
• •4. Active infection including hepatitis
• •5. Any of the following complication:
• •i) Gastrointestinal bleeding or gastrointestinal obstruction (including paralytic ileus) ii) Symptomatic heart disease (including unstable angina, myocardial infarction, and heart failure) iii) Interstitial pneumonia or pulmonary fibrosis iv) Uncontrolled diabetes mellitus v) Uncontrolled diarrhea (that interferes with daily activities despite adequate therapy)
• •6. Any of the following medical history:
• •Myocardial infarction: History of one episode within one year before enrollment or two or more lifetime episodes i) Serious hypersensitivity to any of the study drugs ii) History of adverse reaction to fluoropyrimidines suggesting dihydropyrimidine dehydrogenase (DPD) deficiency
• •7. Previous treatment with irinotecan hydrochloride
• •8. Current treatment with atazanavir sulfate
• •9. Previous treatment with tegafur, gimeracil, and oteracil potassium within seven days before enrollment
• •10. Pregnant or lactating females, and males and females unwilling to use contraception
• •11. Requires continuous treatment with systemic steroids
• •12. Psychiatric disability that would preclude study compliance
• •13. Otherwise determined by the investigator to be unsuitable for participation in the study
• •14. Concurrent gastrointestinal perforation or history of gastrointestinal perforation with 1 year before enrollment
• •15. History of pulmonary hemorrhage/hemoptysis ≥ Grade 2 (defined as bright red blood of at least 2.5mL) within 1 month prior to enrollment.
• •16. History of laparotomy, thoracotomy, or intestinal resection within 28 days before enrollment
• •17. Unhealed wound (except suture wounds from implantation of a central venous port), gastrointestinal ulcer, or traumatic fracture
• •18. Current or recent (within 1 year) thromboembolism or cerebrovascular disease
• •19. Currently receiving or requires anticoagulation therapy (\> 325 mg/day of aspirin)
• •20. Bleeding diathesis, coagulopathy, or coagulation factor abnormality (INR ≥1.5 within 14 days before enrollment)
• •21. Uncontrolled hypertension
• •22. Urine dipstick for proteinuria \>+2