Second Line ColoRectal Cancer Therapy in Combination With Combination of FOL- Folinic Acid(Leucovorin), F - Fluorouracil and OX - Oxaliplatin (FOLFOX) (HORIZON I)

• Objective Response Rate [ Time Frame: Randomisation to data cut-off date of November 2007 ] [ Designated as safety issue: No ]

  Per RECIST Criteria (V1.0) and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >= ##% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

  Confirmed Partial Response (PR) or Complete Response (CR) as defined by RECIST.

• Overall Survival [ Time Frame: Randomisation to data cut-off date of 30 January 2009 ] [ Designated as safety issue: No ]
  Number of months from randomisation to the date of death from any cause
• Quality Of Live(QOL) : Time to Worsening of Tissue Oxygen Index (TOI) [ Time Frame: Randomisation to data cut-off date of November 2007 ] [ Designated as safety issue: No ]
  Time when a sustained clinically important deterioration in TOI has been recorded: derived from the FACT-C questionnaires
• QOL: Time to Worsening of Treatment-free Survival (TFS) [ Time Frame: Randomisation to data cut-off date of November 2007 ] [ Designated as safety issue: No ]
  Time when a sustained clinically important deterioration in TFS has been recorded: derived from the Functional Assessment of Cancer Therapy-Colorectal (FACT-C) questionnaires
• QOL: Time to Worsening of Clear Cell Sarcoma (CCS) [ Time Frame: Randomisation to data cut-off date of November 2007 ] [ Designated as safety issue: No ]
  Time when a sustained clinically important deterioration in CCS has been recorded: derived from the FACT-C questionnaires
• QOL: Time to Worsening of FACT Colorectal Cancer Symptom Index(FCSI) [ Time Frame: Randomisation to data cut-off date of November 2007 ] [ Designated as safety issue: No ]
  Time when a sustained clinically important deterioration in CCS has been recorded: derived from the FACT-C questionnaires

The primary purpose of this study is to compare the efficacy of AZD2171 in combination with FOLFOX to the efficacy of bevacizumab in combination with FOLFOX, in the second-line treatment of patients with metastatic colorectal cancer

• Drug: AZD2171
  oral tablet
  Other Names:

  • cediranib
  • RECENTIN™
• Drug: 5-fluorouracil
  intravenous infusion
  Other Name: 5-FU
• Drug: Leucovorin
  intravenous infusion
• Drug: Oxaliplatin
  intravenous infusion
  Other Name: Eloxatin®
• Drug: Bevacizumab
  intravenous infusion
  Other Name: Avastin®

• Active Comparator: 1
  Bevacizumab + FOLFOX
  Interventions:

  • Drug: 5-fluorouracil
  • Drug: Leucovorin
  • Drug: Oxaliplatin
  • Drug: Bevacizumab
• Experimental: 2
  AZD2171 + FOLFOX
  Interventions:

  • Drug: AZD2171
  • Drug: 5-fluorouracil
  • Drug: Leucovorin
  • Drug: Oxaliplatin

Inclusion Criteria:

• Clinical diagnosis of colon or rectal cancer,
• Received prior systemic therapy for cancer,
• Cancer must have progressed during or after first treatment

Exclusion Criteria:

• Prior treatment with a VEGF inhibitor,
• Poorly controlled hypertension