A Phase II Trial of Weekly Alternating Sequential Administration of BIBF 1120 and BIBW 2992 in Patients With Advanced Colorectal Cancer

Inclusion criteria

• Age over 18 years.
• Signed informed consent.
• Histologically proven colorectal adenocarcinoma
• History or presence of metastatic colorectal cancer (stage IV)
• Measurable (>1 cm) or evaluable tumour deposit (according to RECIST criteria)
• Documented progression or unacceptable toxicity on the last therapy
• Progression on oxaliplatin-based chemotherapy or unacceptable residual neurotoxicity on oxaliplatin
• Progression on irinotecan-based chemotherapy or unacceptable toxicity on irinotecan
• If patients have been previously exposed to Cetuximab or other EGFR inhibitor, they must have shown progression or unacceptable toxicity
• If patients have been previously exposed to Bevacizumab or other VEGF inhibitor, they must have shown progression or unacceptable toxicity
• Life expectancy of at least 12 weeks.
• WHO (ECOG) performance status <= 2, <= 1 if age > 75 years.
• Adequate hepatic function
• Adequate renal function

Exclusion criteria

• Prior treatment with small molecule EGFR, HER2 or VEGFR tyrosine kinase inhibitors
• Treatment with standard chemotherapy or cetuximab within the last 14 days
• Treatment with bevacizumab within the last 28 days
• History of other malignancies in the last 5 years, which could affect compliance with the protocol or interpretation of results. Patients with adequately treated basal or squamous cell skin cancer are generally eligible.
• Serious illness or concomitant non-oncological disease such as neurologic, psychiatric, infectious disease or active ulcers (gastro-intestinal tract, skin) or laboratory abnormality
• Significant cardiovascular diseases
• History of haemorrhagic or thrombotic event in the past 12 months. Known inherited predisposition to bleeds or to thrombosis.
• Patient with history or clinical or radiological evidence of CNS disease or brain metastases.
• Pregnancy or breast-feeding