Irinotecan Plus E7820 Versus FOLFIRI in Second-Line Therapy in Patients With Locally Advanced or Metastatic Colon or Rectal Cancer

Exclusion Criteria

• •1. Received chemotherapy, targeted therapy, radiotherapy, surgery, immunotherapy, or treatment in another clinical study within the 30 days prior to commencing study treatment or have not recovered from side effects of all treatment-related toxicities to Grade less than or equal to 1, except for peripheral neuropathy (Grade 1 and Grade 2 are permitted) and alopecia;
• •2. Previously received irinotecan or irinotecan derivatives in Phase II (irinotecan-containing regimens are allowed in Phase Ib);
• •3. Previously received anti-alpha 2 integrin therapy;
• •4. History of other malignancies except: (1) adequately treated basal or squamous cell carcinoma of the skin; (2) curatively treated in situ carcinoma of the uterine cervix; or (3) other curatively treated solid tumor with no evidence of disease for greater than or equal to 5 years;
• •5. Presence of brain metastases, unless the patient has received adequate treatment at least 4 weeks prior to randomization, and is stable, asymptomatic, and off steroids for at least 4 weeks prior to randomization;
• •6. Are currently receiving any other anticancer treatment;
• •7. Serious non-healing wound, ulcer, or active bone fracture;
• •8. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1, or anticipation of need for a major surgical procedure during the course of the study;
• •9. Refractory nausea and vomiting, malabsorption, significant bowel resection, or any other medical condition that would preclude adequate absorption or result in the inability to take oral medication;
• •10. Significant cardiovascular impairment (history of congestive heart failure New York Heart Association \[NYHA\] Grade greater than 2, unstable angina or myocardial infarction within the past 6 months, or serious cardiac arrhythmia);
• •11. Active hemoptysis (defined as bright red blood of 1/2 teaspoon or more) within the 30 days prior to study entry;
• •12. Current or recent use (within 7 days) of full-dose warfarin (except low-dose warfarin as required to maintain patency of pre-existing, permanent indwelling IV catheters). For patients receiving warfarin, International Normalization Ratio (INR) should be less than 1.5. Patients may have prophylactic use of low molecular weight heparin; however, therapeutic use of heparin or low molecular weight heparin is not acceptable;
• •13. History of bleeding diathesis or coagulopathy;
• •14. Any history of cerebral vascular accident, transient ischemic attack, or Grade greater than or equal to 2 peripheral vascular disease, unless they have had no evidence of active disease for at least 6 months prior to randomization;
• •15. Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 1, unless affected area has been removed surgically;
• •16. Patients with organ allografts requiring immunosuppression;
• •17. Known positive human immunodeficiency virus (HIV), known hepatitis B surface antigen, or active hepatitis C positive;
• •18. Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to irinotecan, 5-FU, or leucovorin;
• •19. Hypersensitivity to sulfonamide derivatives;
• •20. Have any medical condition that would interfere with the conduct of the study.