BIBF 1120 Versus Bevacizumab in Metastatic Colorectal Cancer

• Efficacy of BIBF1120 based on OS, PFS, Overall response rate, resection rate and tumour shrinkage [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
• Appropriate dose of BIBF 1120 in the first 12 to 18 patients when combined with mFolfox6 [ Time Frame: 2 weeks (cycle duration for DLT determination) ] [ Designated as safety issue: No ]
• Safety assessed by the evaluation of the incidence and intensity of adverse events with grading according to the US NCI Common Terminology Criteria for Adverse Events (CTCAE version 3.0) [ Time Frame: up to 1 year ] [ Designated as safety issue: Yes ]
• Pharmacokinetics characteristics of BIBF 1120, 5-FU and oxaliplatin [ Time Frame: up to 1 year ] [ Designated as safety issue: No ]
• Quality of life evaluation by the standardised questionnaires European Organization for Research and Treatment of Cancer Quality of Life Questionnaire ( EORTC-QLQ-C30) and Colorectal Cancer-Specific Quality of Life Questionnaire (EORTC-QLQ-CR38) [ Time Frame: up to 1 year ] [ Designated as safety issue: No ]
• Biomarkers analysis including Vascular Endothelial Growth Factor (VEGF), Fibroblast Growth Factor (FGF), Platelet- Derived Growth Factor (PDGF) plasma levels, Genetic variation, oncogene profile) [ Time Frame: up to 1 year ] [ Designated as safety issue: No ]

The primary objective of this study is to evaluate PFS rate at 9 months of BIBF 1120 in combination with mFolfox6 compared with mFolfox6 combined to bevacizumab in first line patients with metastatic colorectal cancer.

• Drug: BIBF 1120
  BIBF 1120 100 and 150 mg capsules
• Drug: mFolfox
  standard i.v chemotherapy
• Drug: Bevacizumab
  100 mg/Kg solution , IV infusion
• Drug: mFolfox 6
  IV standard chemotherapy
• Drug: bevacizumab
  100 mg/4 ml solution

• Experimental: BIBF 1120 + mFolfox6
  BIBF1120 medium dose twice daily
  Interventions:

  • Drug: BIBF 1120
  • Drug: mFolfox 6
  • Drug: bevacizumab
• Active Comparator: Bevacizumab + mFolfox6
  Bevacizumab 5mg/kg once daily every other week
  Interventions:

  • Drug: BIBF 1120
  • Drug: mFolfox
  • Drug: Bevacizumab

Inclusion criteria:

1. Age >= 18 years
2. Histologically proven colorectal adenocarcinoma
3. No previous oxaliplatin based chemotherapy is allowed unless disease free survival after the end of chemotherapy > = 12 months
4. No previous therapy with VEGFR or EGFR inhibitors
5. No prior systemic therapy for metastatic CRC
6. No previous adjuvant therapy with fluoropyrimidines is allowed unless disease free survival after the end of chemotherapy > 6 months
7. ECOG performance status < = 2
8. Adequate hepatic, renal and bone marrow functions:
9. No uncontrolled hypertension
10. Signed and dated written informed consent prior to admission to the study

Exclusion criteria:

1. Treatment with any investigational drug within 28 days of trial onset.
2. History of other malignancies in the last 5 years, in particular those that could affect compliance with the protocol or interpretation of results.
3. Serious concomitant disease, especially those affecting compliance with trial requirements or which are considered relevant for the evaluation of the efficacy or safety of the trial drug,
4. Major injuries and/or surgery or bone fracture within 4 weeks of trial inclusion, or planned surgical procedures during the trial period.
5. Significant cardiovascular diseases
6. History of severe haemorrhagic or thromboembolic event in the past 12 months. Known inherited predisposition to bleeding or to thrombosis.
7. Patient with brain metastases that are symptomatic and/or require therapy.
8. Pregnancy or breast-feeding.