Neoadjuvant Radiotherapy for Rectal Adenocarcinoma With Capecitabine Versus TAS-102 (Neo-REACT): A Multi-center, Randomized, Phase III Trial

Neoadjuvant fluoropyrimidine-based chemoradiotherapy (nCRT) followed by TME is the standard care for LARC. However, the tumor responses to nCRT cover a wide spectrum and the complete pathologic response rate varies from 8% to 20%. The low rate of pCR after neoadjuvant therapy could not satisfy patients with distal rectal cancer who want to keep anal function. Therefore, currently, the addition of other agents to 5-FU or capecitabine as components of the multimodality treatment for LARC outside of clinical trials is not recommended in clinical practice. TAS-102 is a new oral anti-tumor oral formulation of nucleoside analogue, FTD, and a thymidine phosphorylase inhibitor, TPI. TPI improves the bioavailability and ensures sufficient blood concentrations of FDT. Previous studies have shown that TAS-102 has shown clinically relevant activity after fluoropyrimidine failure in colorectal cancer and may thus be of increased efficacy compared with current standard capecitabine chemoradiation. Also, a phase 2 trials conducted by our team have demonstrated that neoaduvant TAS-102 concurrent with long-course radiotherapy could lead to a high pCR rate of 32% with acceptable toxicity for LARC patients. Herein, we will conduct this multicenter, randomized controlled, phase III trial to explore the safety and efficacy benefit of TAS-102 concurrent with long-course radiotherapy for LARC.