Nintedanib (BIBF 1120) vs Placebo in Refractory Metastatic Colorectal Cancer (LUME-Colon 1)
Condition: Colorectal Neoplasms
MeSH terms: Colorectal Neoplasms
Intervention: Nintedanib (BIBF 1120); Placebo; BSC; BSC
Intervention MeSH terms: Nintedanib
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Enrollment: 768.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The objective of this Phase III study is to evaluate the efficacy of nintedanib in patients
      with metastatic colorectal cancer (mCRC) after failure of previous treatment with standard
      chemotherapy and biological agents.
    

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          -  Progression on standard therapies or withdrawn from standard treatment due to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