A Study of Avastin (Bevacizumab) Plus Crossover Fluoropyrimidine-Based Chemotherapy in Patients With Metastatic Colorectal Cancer.

• Overall survival from time of starting first-line therapy [ Time Frame: approximately 6.5 years ] [ Designated as safety issue: No ]
• Progression-free survival (after first progression) [ Time Frame: approximately 6.5 years ] [ Designated as safety issue: No ]
• Response rate, tumor assessments according to RECIST criteria [ Time Frame: approximately 6.5 years ] [ Designated as safety issue: No ]
• Safety: Incidence of adverse events [ Time Frame: approximately 6.5 years ] [ Designated as safety issue: No ]

• Overall survival; response rate. [ Time Frame: Event driven ] [ Designated as safety issue: No ]
• AEs, laboratory parameters. [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

This study will evaluate the efficacy and safety of adding Avastin (bevacizumab) to crossover fluoropyrimidine-based chemotherapy in patients with metastatic colorectal cancer who have experienced disease progression under first line treatment with standard chemotherapy plus Avastin. Patients will be randomized to one of 2 chemotherapy strata. Those in stratum 1 will receive chemotherapy (AIO-IRI, FOLFIRI, CAPIRI or XELIRI) alone, or in combination with Avastin (5mg/kg iv on days 1 and 14 of each 4 week cycle or 7.5mg/kg on days 1 and 22 of each 6 week cycle) and those in stratum 2 will receive chemotherapy (FUFOX, FOLFOX, CAPOX or XELOX) alone, or in combination with Avastin (5mg/kg on days 1 and 14 of each 4 week cycle or 7.5mg/kg on days 1 and 22 of each 6 week cycle). The anticipated time on study treatment is until disease progression or unacceptable toxicity occurs.

• Drug: bevacizumab [Avastin]
  5mg/kg iv on days 1 and 14 of each 4 week cycle, or 7.5mg/kg on days 1 and 22 of each 6 week cycle.
• Drug: AIO-IRI, FOLFIRI, CAPIRI or XELIRI
  As prescribed
• Drug: FUFOX, FOLFOX, CAPOX or XELOX
  As prescribed

• Experimental: Chemotherapy 1 + Avastin
  Interventions:

  • Drug: bevacizumab [Avastin]
  • Drug: AIO-IRI, FOLFIRI, CAPIRI or XELIRI
• Experimental: Chemotherapy 2 + Avastin
  Interventions:

  • Drug: bevacizumab [Avastin]
  • Drug: FUFOX, FOLFOX, CAPOX or XELOX
• Active Comparator: Chemotherapy 1
  Intervention: Drug: AIO-IRI, FOLFIRI, CAPIRI or XELIRI
• Active Comparator: Chemotherapy 2
  Intervention: Drug: FUFOX, FOLFOX, CAPOX or XELOX

Inclusion Criteria:

• Adult patients, >=18 years of age
• Metastatic colorectal cancer and disease progression
• Previously treated with first-line chemotherapy plus Avastin
• ECOG <=2.

Exclusion Criteria:

• Diagnosis of progression of disease more than 3 months after last Avastin administration
• First-line patients with progression-free survival in first-line of <3 months
• Patients receiving less than 3 consecutive months of Avastin in first-line therapy
• Past or current history (within the last 2 years prior to treatment start) of other malignancies, except for curatively treated basal and squamous cell cancer of the skin or in situ cancer of the cervix
• Clinically significant cardiovascular disease within 6 months prior to start of study treatment
• Known CNS disease, except for treated CNS metastases as defined by protocol