Assessment of Management and Anti-inflammatory Therapy Effectiveness in Colorectal cancer: Randomized Assessment of Supplemental Hochuekkito Therapy: Study protocol for a multicenter randomized controlled trial (AMATERAS study)

Background Systemic inflammation, a hallmark of cancer, is recognized as a key mechanism underlying malnutrition, sarcopenia, and cancer cachexia. Hochuekkito (TJ-41) is a traditional Japanese Kampo formula composed of ten medicinal plants, and several studies have suggested its anti-inflammatory effects in various diseases. Our recent retrospective study, supported by in vitro experiments, was the first to demonstrate an anti-inflammatory effect of TJ-41 in patients with unresectable or metastatic gastrointestinal cancer, including colorectal cancer (CRC). However, no prospective randomized multicenter clinical trial has evaluated TJ-41 in the palliative setting of malignancies, including CRC. Methods Patients with unresectable or metastatic CRC who have received at least two prior systemic regimens or are intolerant to standard therapy, and who show an elevated C-reactive protein (CRP) level > 0.5 mg/dL on two consecutive occasions within two months before enrollment, will be eligible. After providing written informed consent, patients will be randomly assigned to Treatment group (standard treatment plus TJ-41) or Control Group (standard treatment alone). Patients in Treatment Group will receive oral TJ-41 (Tsumura & Co., Tokyo, Japan) at 7.5 g/day, divided into three doses (2.5 g per dose), before or between meals for 12 weeks. The primary endpoint is the difference in anti-inflammatory effect between groups, assessed by the change in CRP from baseline to 12 weeks. Secondary endpoints include the effects of TJ-41 on other inflammatory and nutritional parameters; patient-reported symptoms and quality of life (QOL) using QOL-ACD and EORTC QLQ-C30; cytokine-based anti-inflammatory and anti-cachectic effects using serial blood specimens; interactions with other appetite-stimulating agents or nutritional products; and effects on antitumor efficacy and adverse events. Each group will include 44 patients, with recruitment planned from July 1, 2024, to December 31, 2026. Discussion This trial will evaluate whether TJ-41 can attenuate systemic inflammation related to host–tumor interactions in patients with unresectable or metastatic CRC. Trial registration: This study was registered in the Japan Registry of Clinical Trials on June 26, 2024 (jRCTs041240051).