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- Progression on standard therapies or withdrawn from standard treatment due to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 oxalipatin 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 Tranferase (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.