Randomized controlled trial of the significance of combined use with Ninjin’yoeito in CapeOX + Bmab therapy for patients with unresectable advanced/recurrent colorectal cancer

Background: This randomized controlled trial is aimed at clarifying the benefit of an extract of ninjin’yoeito (NYT, traditional Japanese herbal medicine, Kampo) when combined with capecitabine plus oxaliplatin (CapeOX) plus bevacizumab (Bmab) in 150 patients with metastatic or recurrent colorectal cancer with special reference to nutritional status. Methods/Design: Patients with unresectable, metastatic, or recurrent colorectal cancer who plan to receive CapeOX + Bmab will be recruited. Of these patients, those who provide written informed consent will be randomly allocated to the NYT group (NYT + CapeOX + Bmab) or the control group (CapeOX + Bmab). The co-primary endpoints will be nutritional status, evaluated with CONtrolling NUTritional Status scores, and severe non-hematological adverse events, assessed using the Common Terminology Criteria for Adverse Events v5.0. The secondary endpoints will include the interaction between NYT and capecitabine; quality of life evaluated using the European Organization for Research and Treatment of Cancer-QLQ-C30; relative dose intensity of oxaliplatin, capecitabine, and bevacizumab; and plasma levels of phosphorylated neurofilament heavy chain. The two groups will include 75 patients each, and the patient recruitment period is January 1st, 2020 to December 31st, 2022. Discussion: This trial evaluates the efficacy and safety of NYT in the maintenance of a better nutritional status and fewer adverse events during the standard chemotherapeutic regimen of CapeOX + Bmab administered to patients with advanced or recurrent colorectal cancer. The potential implications include that NYT could be a strong supportive therapy in patients with colorectal cancer receiving chemotherapy. Trial registration number: This study was registered in the Japan Registry of Clinical Trials (registration number: jRCTs041190071) on October 2, 2019.