Clinical trial NCT02149108 (phase 3, status: completed)
Conditions: colorectal neoplasms
ICD codes: C05.2, C10.0, C16.0, C16.4, C17.0, C17.1, C17.2
Drugs: nintedanib (bibf 1120), placebo, bsc, bsc
SMILES: COC(=O)C1=CC=C2C(NC(=O)\C2=C(/NC2=CC=C(C=C2)N(C)C(=O)CN2CCN(C)CC2)C2=CC=CC=C2)=C1, CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
Eligibility criteria:

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          -  Progression on standard therapies or withdrawn from standard treatment due to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