A Study Combining FOLFOX or FOLFIRI With AG-013736 or Bevacizumab (Avastin) in Patients With Metastatic Colorectal Cancer After Failure Of One First Line Regimen

• Drug: Bevacizumab (avastin)
  
  Bevacizumab intravenous [IV] infusion 5 mg/kg every two weeks until disease progression, intolerance or withdrawal of consent.
• Drug: FOLFIRI (Irinotecan, leucovorin, 5-fluorouracil [5FU])
  
  Irinotecan (180 mg/m²) intravenous infusion [IV] over 90 minutes, concurrently with leucovorin (400 mg/m²) intravenous infusion [IV] over 2 hours followed immediately by 5-FU bolus (400 mg/m²) intravenous [IV] and a subsequent 5-FU infusion (2400 mg/m² over 46-48 hours), repeated every 2 weeks until disease progression, intolerance or withdrawal of consent.
• Drug: AG-013736 (axitinib)
  
  Axitinib is given at a starting dose of 5 mg twice daily [BID] continuous dosing until disease progression, intolerance or withdrawal of consent.
• Drug: FOLFOX (oxaliplatin, leucovorin, 5-fluorouracil [5FU])
  
  Oxaliplatin (85 mg/m²) intravenous infusion [IV] over 120 minutes, concurrently with leucovorin (400 mg/m²) intravenous infusion [IV] over 2 hours followed by 5-FU IV bolus (400 mg/m²) and a subsequent 5-FU IV infusion (2400 mg/m² over 46-48 hours), repeated every 2 weeks until disease progression, intolerance or withdrawal of consent.
• Drug: FOLFIRI (irinotecan, leucovorin, 5-fluorouracil [5FU])
  
  Irinotecan (180 mg/m²) intravenous infusion [IV] over 90 minutes, concurrently with leucovorin (400 mg/m²) intravenous infusion [IV] over 2 hours followed immediately by 5-FU bolus (400 mg/m²) IV and a subsequent 5-FU IV infusion (2400 mg/m² over 46-48 hours), repeated every 2 weeks until disease progression, intolerance or withdrawal of consent.
• Drug: Bevacizumab (avastin)
  
  Bevacizumab intravenous infusion [IV] 5 mg/kg every two weeks until disease progression, intolerance or withdrawal of consent.
• Drug: FOLFOX (oxaliplatin, leucovorin, 5-fluorouracil [5FU])
  
  Oxaliplatin (85 mg/m²) IV infusion over 120 minutes, concurrently with leucovorin (400 mg/m²) intravenous infusion [IV] over 2 hours followed by 5-FU IV bolus (400 mg/m²) and a subsequent 5-FU IV infusion (2400 mg/m² over 46-48 hours), repeated every 2 weeks until disease progression, intolerance or withdrawal of consent.

• Active Comparator: B
  
  Bevacizumab (avastin)
  Interventions:
  

  • Drug: Bevacizumab (avastin)
  • Drug: FOLFIRI (Irinotecan, leucovorin, 5-fluorouracil [5FU])
• Experimental: C
  
  AG-013736 (axitinib)
  Interventions:
  

  • Drug: AG-013736 (axitinib)
  • Drug: FOLFOX (oxaliplatin, leucovorin, 5-fluorouracil [5FU])
• Experimental: A
  
  AG-013736 (axitinib)
  Interventions:
  

  • Drug: AG-013736 (axitinib)
  • Drug: FOLFIRI (irinotecan, leucovorin, 5-fluorouracil [5FU])
• Active Comparator: D
  
  bevacizumab (avastin)
  Interventions:
  

  • Drug: Bevacizumab (avastin)
  • Drug: FOLFOX (oxaliplatin, leucovorin, 5-fluorouracil [5FU])

Inclusion Criteria:

• Histologically documented colorectal cancer plus one of the following:
• Failure of one prior irinotecan- or oxaliplatin-containing regimen, or
• Adjuvant refractory to irinotecan- or oxaliplatin-containing regimen.

Exclusion Criteria:

• Prior treatment in first line metastatic setting with more than one regimen
• Prior irradiation of more than 25% of bone marrow.