Nintedanib (BIBF 1120) vs Placebo in Refractory Metastatic Colorectal Cancer (LUME-Colon 1)

Inclusion criteria

• Age >= 18 years
• Signed informed consent
• Histologically or cytologically confirmed colorectal adenocarcinoma
• Metastatic or locally advanced disease not amenable to curative surgery and/or radiotherapy
• Eastern Cooperative Oncology Group (ECOG) performance status = 1
• At least one measurable lesion according to Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1
• Progression on standard therapies or withdrawn from standard treatment due to unacceptable toxicity. Previous standard treatment must include all of the following:
• - fluoropyrimidine
• - oxaliplatin: Patients treated with oxaliplatin in adjuvant setting should have progressed within 6 months of completion of adjuvant therapy or they must have been treated with oxaliplatin for metastatic disease
• - irinotecan
• - bevacizumab or aflibercept
• - cetuximab or panitumumab for patients with K-Ras wt or Ras wt tumours
• - The remaining standard available therapy as recommended by investigator is best supportive care (note: previous treatment with regorafenib and TAS 102 are allowed and these agents should be administered before study if available to patient according to local standards)
• - Life expectancy of at least 12 weeks
• - Hepatic function: aspartate aminotransferase (AST)/ Alanine Amino Transferase (ALT) = 1.5 X Upper Limit of Normal (ULN) and bilirubin = ULN for patients without liver metastases. AST/ALT = 2.5 X ULN and bilirubin = ULN for patients with liver metastases. Patients with Gilbert syndrome and bilirubin < 2 X ULN and normal AST/ALT are eligible
• Coagulation parameters: International normalised ratio (INR) < 2 and partial prothrombin Time (PTT) = 2xULN

Exclusion criteria

• Previous treatment with nintedanib
• toxicity attributed to previous anticancer therapy that did not resolve to Common Terminology Criteria for Adverse Events (CTCAE) grade =1
• History of other malignancies in the last 5 years, in particular those that could interfere with interpretation of results.
• Serious concomitant disease or medical condition affecting compliance with trial requirements or which are considered relevant for the evaluation of the efficacy or safety of the trial drug,
• Significant cardiovascular diseases
• History of severe haemorrhagic or thromboembolic event in the past 12 months
• Bleeding or thrombotic disorders requiring anticoagulant therapy such as warfarin, or similar agents requiring therapeutic INR monitoring
• Gastrointestinal disorders or abnormalities that would interfere with absorption of study drug
• Patient with brain metastases that are symptomatic and/or require therapy.
• Patients of childbearing potential who are sexually active and unwilling to use a highly effective method of contraception
• Pregnancy or breast-feeding.