Nintedanib Alone or in Combination With Capecitabine in Refractory Metastatic Colorectal Cancer [LUME-Colon 2]

LUME-Colon 2: An Open-label Randomized Phase II Study to Assess the Efficacy and Safety of Nintedanib Alone or in Combination With Capecitabine for Patients With Refractory Metastatic Colorectal Cancer

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

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