A Study of RO5083945 in Combination With FOLFIRI Versus FOLFIRI Plus Cetuximab or FOLFIRI Alone as Second Line Treatment in Patients With Metastatic Colorectal Cancer

• Overall Response Rate: tumour assessments by CT scan or MRI according to RECIST criteria [ Time Frame: approximately 18 months ] [ Designated as safety issue: No ]
• Duration of response: time from complete or partial response to disease progression or death [ Time Frame: approximately 18 months ] [ Designated as safety issue: No ]
• Clinical benefit rate: stable disease for >6 weeks, complete response or partial response; tumour assessments by CT scan or MRI according to RECIST criteria [ Time Frame: approximately 18 months ] [ Designated as safety issue: No ]
• Overall survival [ Time Frame: approximately 18 months ] [ Designated as safety issue: No ]
• Safety: Incidence of adverse events [ Time Frame: approximately 18 months ] [ Designated as safety issue: No ]
• Effect of concomitant FOLFIRI on pharmacokinetics of RO5083945 and vice versa [ Time Frame: approximately 18 months ] [ Designated as safety issue: No ]

This randomized, multicenter, open label study will evaluate the safety and efficacy of RO5083945 in combination with FOLFIRI as compared to FOLFIRI plus cetuximab or FOLFIRI alone as second line treatment in patients with metastatic colorectal cancer. Patients will be randomized to receive RO5083945 (1400 mg intravenously on Day 1 and Day 8 and every 2 weeks thereafter) plus FOLFIRI standard iv chemotherapy or FOLFIRI plus cetuximab (400 mg/m2 iv on Day 1 followed by 250 mg/m2 iv every week) or FOLFIRI alone. Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs.

• Drug: RO5083945
  1400 mg iv on Day 1 and Day 8, and every 2 weeks thereafter
• Drug: FOLFIRI
  standard iv chemotherapy
• Drug: cetuximab
  400 mg/m2 iv on Day 1, followed by 250 mg/m2 iv every week

• Experimental: KRAS WT A
  Interventions:

  • Drug: RO5083945
  • Drug: FOLFIRI
• Active Comparator: KRAS WT B
  Interventions:

  • Drug: FOLFIRI
  • Drug: cetuximab
• Experimental: KRAS mutant A
  Interventions:

  • Drug: RO5083945
  • Drug: FOLFIRI
• Active Comparator: KRAS mutant B
  Intervention: Drug: FOLFIRI

Inclusion Criteria:

• Adult patients, >/= 18 years of age
• Carcinoma of the colon and/or rectum
• Disease progression during or within 6 months of last dose of oxaliplatin containing first-line combination therapy for metastatic disease
• ECOG performance status 0-1
• Adequate hematological, renal and liver function

Exclusion Criteria:

• Prior treatment with monoclonal antibody/small molecule against epidermal growth factor receptor (EGFR)
• Prior treatment with irinotecan
• Radiotherapy within the last 4 weeks before first dose of study drug (except for limited field palliative radiotherapy for bone pain relief)
• CNS metastasis
• History of or active autoimmune disorders/conditions