title: Rationale and Design for the LUME-Colon 1 Study: A Randomized, Double-Blind, Placebo-Controlled Phase III Trial of Nintedanib Plus Best Supportive Care Versus Placebo Plus Best Supportive Care in Patients With Advanced Colorectal Cancer Refractory to Standard Treatment.
abstract: BACKGROUND
  Clinical studies of antivascular endothelial growth factor (anti-VEGF) agents have demonstrated that angiogenesis is critical to colorectal cancer (CRC) tumor growth and metastasis. Nintedanib is a triple angiokinase inhibitor of VEGF, platelet-derived growth factor, and fibroblast growth factor signaling. Nintedanib, combined with docetaxel, has been approved in the European Union for the treatment of patients with non-small-cell lung cancer with adenocarcinoma tumor histologic type after first-line chemotherapy. The objective of the present study (1199.52; clinicaltrials.gov identifier NCT02149108; LUME-Colon 1) is to evaluate the efficacy and safety of nintedanib plus best supportive care (BSC) in patients with advanced colorectal cancer refractory to standard chemotherapy regimens and biologic agents.
  
  
  METHODS
  A total of 764 patients worldwide will be randomized 1:1 to receive either nintedanib 200 mg twice daily plus BSC or placebo plus BSC in 21-day courses until disease progression, undue toxicity, or withdrawal of informed consent. The primary endpoints are progression-free survival (PFS) and overall survival (OS). The secondary endpoints are the objective tumor response and disease control. PFS and OS will be evaluated using a log-rank test to determine the effect of nintedanib independently at the 2-sided α-level of 0.05. Other assessments will include the frequency and severity of adverse events and changes in laboratory parameters to measure the safety, health-related quality of life, and pharmacogenomic analyses, focusing on exploring the predictive biomarkers and drug-resistance mechanisms. The results are expected in 2016.
authors.affiliation: Digestive Oncology, University Hospitals Leuven, Leuven, Belgium. Electronic address: eric.vancutsem@uzleuven.be.
authors.forename: Eric
authors.initials: E
authors.lastname: Van Cutsem
authors.affiliation: Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Chiba, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Yoshino
authors.affiliation: Biometrics and Data Management, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Hocke
authors.affiliation: Biometrics and Data Management, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany.
authors.forename: Zohra
authors.initials: Z
authors.lastname: Oum'Hamed
authors.affiliation: Division of Medicine, Clinical Development Department, Boehringer Ingelheim, Vienna, Austria.
authors.forename: Matus
authors.initials: M
authors.lastname: Studeny
authors.affiliation: Medical Oncology Department, Vall d'Hebron University Hospital, Barcelona, Spain.
authors.forename: Josep
authors.initials: J
authors.lastname: Tabernero
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D004311:Double-Blind Method; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D057194:Intention to Treat Analysis; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D015996:Survival Rate; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; C530716:nintedanib
keywords: Angiogenesis; Colorectal; FGF; PDGF; TKI; VEGF