LUME-Colon 1: a randomized phase III study of nintedanib vs placebo in patients with advanced colorectal cancer

Abstract

Background: Angiogenesis is critical to colorectal cancer (CRC) tumor growth and metastasis. Regorafenib (R) has provided proof of principle in patients ( pts) with refractory CRC, but is associated with a specific safety profile; there is a need for effective alternative treatments with different safety profiles. Nintedanib (N) is a triple angiokinase inhibitor of VEGF, PDGF and FGF signaling. N is approved in the European Union for the treatment of pts with adenocarcinoma NSCLC after 1st‐line chemotherapy and has shown clinical benefit in trials in several tumor types. In a Phase I study of N in CRC, a clinically relevant anti‐angiogenic effect was observed in 67% of pts. These findings and a manageable safety profile provide a rationale to examine N in CRC. The objective of this Phase III study (NCT02149108; 1199.52) is to evaluate the efficacy and safety of N in pts with advanced CRC after failure of standard chemotherapy and biologic agents. Methods: 764 pts worldwide (age ≥18 years, ECOG‐PS 0/1 and histologically/ cytologically confirmed colorectal adenocarcinoma unamenable to surgery and/or radiotherapy) will be randomized 1:1 to receive either N + best supportive care (BSC) or placebo + BSC in 21‐day courses until disease progression or undue toxicity. The study is powered to distinguish a clinically meaningful effect in the co‐primary endpoints PFS and OS. Secondary endpoints are objective tumor response and disease control. Pts will be stratified at randomization based on previous R treatment, time from onset of metastatic disease to randomization and region. PFS and OS will be evaluated by the log‐rank test to determine the effect of N independently at the 2‐sided alpha level of 0.05. Other assessments include frequency and severity of adverse events and changes in laboratory parameters to measure safety; health‐related quality of life; and analyses to explore predictive biomarkers and drug resistance mechanisms. Results are expected in 2016.