Phase III Randomized Study of 5-FU, CoFactor, and Avastin vs. 5-FU, LV and Avastin for First-Line Colorectal Cancer.

Exclusion Criteria

• •1. Any prior exposure to bevacizumab.
• •2. A known intolerance to fluoropyrimidine (5-FU, capecitabine, floxuridine, UFT) therapy suggestive of dihydropyrimidine dehydrogenase (DPD) deficiency.
• •3. Use of the following drugs are not permitted on the protocol: sorivudine (or other nucleoside analogue), or Brivudin™ (or other DPD inhibitor).
• •4. Pregnancy or lactation. Women with a positive (or no) serum or urine pregnancy test within 15 days of Cycle 1 Week 1. Women must have been amenorrheic for at least 12 consecutive months to be considered to lack potential for child bearing.
• •5. If sexually active and of child-bearing potential, failure to agree to use adequate contraception during this study and for 60 days after discontinuation of study medication.
• •6. A concurrent infection, including diagnoses of FUO and evidence of possible central line sepsis (subjects must be afebrile at the start of therapy).
• •7. Any unstable oncologic emergency syndromes: superior vena cava syndrome, rising bilirubin needing stent placement, spinal cord compression, active bleeding, etc.
• •8. History of CNS metastasis, or other brain tumor, or history of stroke.
• •9. Radiation therapy within 6 weeks of Cycle 1 Week 1, or any radiation therapy which encompasses target lesions selected for this study unless those lesions have documented progression of disease.
• •10. Major surgery, open biopsy, or significant traumatic injury within 4 weeks of Cycle 1 Week 1, or anticipated need for major surgical procedure during the course of the study.
• •11. Fine needle aspiration or placement of a central line catheter within 7 days of Cycle 1 Week 1.
• •12. Inadequate bone marrow, liver or kidney function defined as:
• •* Serum creatinine more than 1.5 times the upper limit of normal,
• •* Urine protein to creatinine ratio \>1,
• •* Serum bilirubin \> 2 times the upper limit of normal,
• •* ANC \< 1.5 x 109/L,
• •* Hemoglobin \< 9.0 g / dL
• •* Platelet count \< 90 x 109/L,
• •* SGOT (AST) and SGPT (ALT) more than 3 times the upper limit of normal, or more than 5 times the upper limit of normal for subjects with documented liver metastases.
• •13. Myocardial infarction, transient ischemic attack, cerebral bleeding, translumenal cardiac angiography or cardiac stent placement or other arterial thrombotic event within 12 months prior to Cycle 1 Week 1.
• •14. Active, clinically significant cardiovascular or symptomatic arterial peripheral vascular disease \[e.g., uncontrolled hypertension, congestive heart failure, claudication, unstable angina, symptomatic cardiac arrhythmia, or New York Heart Association (NYHA) Class 2 or greater\].
• •15. Presence of serious non-healing wounds, gastro-duodenal ulcers active by endoscopy, gastro-intestinal perforation or intra-abdominal abscess, skin ulcers, or bone fractures.
• •16. INR \>1.5 unless on therapeutic doses of oral anticoagulants (e.g. warfarin). If so, must have an in-range INR (usually between 2-3) on a stable dose of drug.
• •17. Participation in another experimental drug study within 4 weeks prior to Cycle 1 Week 1.
• •18. Known or suspected anaphylaxis reaction to leucovorin or any allergic reaction to a drug which, in the opinion of the Investigator, suggests an increased potential for a hypersensitivity to CoFactor or other study drug including excipients.
• •19. Presence of organ allograft requiring immunosuppressive therapy.
• •20. Unwilling or unable to comply with the study protocol or history of psychiatric disability judged by the investigator to preclude granting of informed consent.