A Study of Avastin (Bevacizumab) in Combination With mFOLFOX-6 or FOLFOXIRI in Patients With Metastatic Colorectal Cancer.

• Histopathological response; relapse-free survival; progression-free survival; overall survival; overall response rate; time to response; surgical safety. [ Time Frame: Event driven ] [ Designated as safety issue: No ]
• Surgical safety (wound healing complications, bleeding) [ Time Frame: 48hrs, 1 months and 3 months post-durgery for surgical safety ] [ Designated as safety issue: No ]
• SAEs [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

This 2 arm study will compare the resection rate of liver metastases and safety of surgery in patients with metastatic colorectal cancer and primarily unresectable liver metastases receiving treatment with Avastin in combination with 5-FU, leucovorin and oxaliplatin with irinotecan (FOLFOXIRI) or without irinotecan (mFOLFOX-6) as first line treatment. Patients will be randomized to receive Avastin (5mg/kg iv every 2 weeks) in combination with each of these two standard neoadjuvant chemotherapy regimens. The anticipated time on study treatment is until surgery, disease progression, unacceptable toxicity or patient refusal, and the target sample size is <100 individuals.

• Drug: bevacizumab [Avastin]
  5mg/kg iv day 1 every 2 weeks
• Drug: Oxaliplatin
  85mg/m2 2-hour iv infusion, day 1 every 2 weeks
• Drug: Leucovorin
  400mg/m2 2-hour iv infusion, day 1 every 2 weeks
• Drug: 5-FU
  Bolus 400mg/m2, day 1 every 2 weeks
• Drug: 5-FU
  2400mg/m2 46-hour continuous iv infusion, day 1 every 2 weeks
• Drug: Leucovorin
  200mg/m2 2-hour iv infusion, day 1 every 2 weeks
• Drug: 5-FU
  3200mg/m2 46-hour continuous iv infusion, day 1 every 2 weeks
• Drug: Irinotecan
  165mg/m2 1-hour iv infusion, day 1 every 2 weeks

• Experimental: 1
  Interventions:

  • Drug: bevacizumab [Avastin]
  • Drug: Oxaliplatin
  • Drug: Leucovorin
  • Drug: 5-FU
  • Drug: 5-FU
• Active Comparator: 2
  Interventions:

  • Drug: bevacizumab [Avastin]
  • Drug: Oxaliplatin
  • Drug: Leucovorin
  • Drug: 5-FU
  • Drug: Irinotecan

Inclusion Criteria:

• adult patients, >=18 and <=70 years of age;
• unresectable liver metastasis secondary to cancer of colon or rectum;
• scheduled for standard first line chemotherapy;
• ECOG performance score of 0 or 1;
• condition feasible for major abdominal surgery after first line treatment.

Exclusion Criteria:

• diagnosis of metastatic disease >3 months prior to study entry;
• evidence of extrahepatic disease, diffuse peritoneal carcinosis or involvement of celiac lymph nodes;
• prior systemic or local treatment of metastatic disease;
• prior (neo)adjuvant chemotherapy/radiotherapy completed within 6 months prior to study entry;
• history or evidence of CNS disease unrelated to cancer.