Nintedanib Alone or in Combination With Capecitabine in Refractory Metastatic Colorectal Cancer [LUME-Colon 2]
Condition: Colorectal Neoplasms
MeSH terms: Colorectal Neoplasms
Intervention: Nintedanib; Capecitabine
Intervention MeSH terms: Capecitabine; Nintedanib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The objective of this Phase II study is to assess the efficacy and safety of nintedanib alone
      or in combination with capecitabine for patients with refractory metastatic colorectal cancer
      (mCRC) after failure of at least 2 lines of standard treatment
    

Eligibility criteria:

        Inclusion criteria:

          -  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 RECIST 1.1

          -  Previously treated with all of the following: fluoropyrimidine, (e.g. 5-fluorouracil
             (5-FU), capecitabine or TAS-102); 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; Vascular Endothelial Growth Factor (VEGF) directed treatment (e.g.
             bevacizumab, aflibercept, ramucirumab or regorafenib); cetuximab or panitumumab for
             patients with K-Ras wt or Ras wt tumors

          -  Minimal time interval of 3 weeks between the last administration of Colorectal Cancer
             (CRC) treatment (cytotoxics or targeted agents) and starting of trial therapy

          -  Adequate liver and kidney function

          -  Further inclusion criteria apply

        Exclusion criteria:

          -  Prior treatment with nintedanib.

          -  Any other investigational agent received within 3 weeks prior to randomization

          -  Known hypersensitivity or intolerability to the trial drugs or their excipients

          -  History of other malignancies in the last 5 years, in particular those that could
             interfere with interpretation of results. Patients with adequately treated basal or
             squamous cell skin cancer or cervix carcinoma and other early stage cancer treated
             curatively are eligible

          -  History of severe or unexpected reactions to fluoropyrimidine therapy or any of its
             excipients

          -  Known dihydropyrimidine dehydrogenase (DPD) deficiency

          -  Treatment with sorivudine or its chemically related analogues, such as brivudine

          -  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, such as neurologic, psychiatric, infectious disease or
             active ulcers (gastro-intestinal tract, skin) or laboratory abnormality that may
             increase the risk associated with trial participation or trial drug administration,
             and in the judgment of the investigator would make the patient inappropriate for entry
             into the trial

          -  Major injuries and/or surgery or bone fracture within 4 weeks of trial inclusion
             (signing Informed Consent), or planned surgical procedures during the trial period

          -  Significant cardiovascular diseases (i.e. uncontrolled hypertension, unstable angina,
             history of myocardial infarction within past 6 months of trial inclusion, congestive
             heart failure > New York Heart Association (NYHA) II)

          -  History of severe hemorrhagic or thromboembolic event in the past 6 months (excluding
             central venous catheter thrombosis and peripheral deep vein thrombosis). Known
             inherited predisposition to bleeding or to thrombosis

          -  Bleeding or thrombotic disorders requiring anticoagulant therapy such as warfarin, or
             similar agents requiring therapeuticInternational normalized ratio (INR) monitoring
             (treatment with low molecular weight heparin and/or heparin flush as needed for
             maintenance of an indwelling intravenous device is allowed)

          -  Inflammatory bowel disease and other serious medical conditions increasing the risk of
             perforation or bleeding according to investigator's judgment

          -  Gastrointestinal disorders or abnormalities that would interfere with absorption of
             study drug

          -  Patient with brain metastases that are symptomatic and/or require therapy. Patients
             with previously treated and stable brain metastases are allowed

          -  Further exclusion criteria apply