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

Study Overview
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Brief Summary
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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

Official Title
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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

Conditions
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Colorectal Neoplasms

Intervention / Treatment
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* Drug: Nintedanib
* Drug: Capecitabine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nintedanib<br> | Drug: Nintedanib<br> <br> |
| Experimental: Nintedanib plus capecitabine<br> | Drug: Nintedanib<br> <br> Drug: Capecitabine<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | PFS is defined as the time from randomization until objective tumor progression or death. Since only one patient was enrolled prior to termination of the trial, no data summarization or analysis was carried out. | Data collected up to cut-off date 09 Sep 2016, Up to 02 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | Overall survival is defined as the time from randomization until death from any cause. Since only one patient was enrolled prior to termination of the trial, no data summarization or analysis was carried out. | Data collected up to cut-off date 09 Sep 2016, Up to 02 months | 
| Objective Response Rate (ORR) | ORR is defined as complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Since only one patient was enrolled prior to termination of the trial, no data summarization or analysis was carried out. | tumor response was to be assessed by imaging according to RECIST (version 1.1) every 6 weeks. | 
| Disease Control (DC) | Disease control is defined as CR or PR or Stable disease (SD) per RECIST version 1.1. Since only one patient was enrolled prior to termination of the trial, no data summarization or analysis was carried out. | Data collected up to cut-off date 09 Sep 2016, Up to 02 months | 
| Percentage of Patients With Grade 3 or Worse Adverse Events | Percentage of patients with grade 3 or worse adverse events. | Data collected up to cut-off date 09 Sep 2016, Up to 02 months |