A randomized controlled trial evaluating the effects of anamorelin in postoperative patients with upper gastrointestinal cancer: protocol for the CLEAR-UP study

Abstract Patients undergoing curative surgery for upper gastrointestinal (UGI) cancers often experience substantial postoperative weight loss and reduction in muscle mass, one contributing factor being decreased ghrelin secretion following surgery. Anamorelin, a ghrelin receptor agonist, has been shown to improve appetite and increase lean body mass in patients with cancer cachexia; however, its efficacy in the postoperative setting has not been established. The CLEAR-UP study is a multicenter, open-label, randomized controlled trial designed to investigate the clinical effects of anamorelin in patients who have undergone curative resection for gastric or esophageal cancer. A total of 160 patients will be randomly assigned in a 1:1 ratio to receive either anamorelin (100 mg orally once daily for 12 weeks) or standard postoperative care without pharmacological intervention. Randomization will be stratified by cancer type (gastric vs. esophageal) and baseline body mass index (BMI 18.5 vs. ≥18.5). All patients will be followed for 48 weeks. The primary endpoint is the percent change in lean body mass at 12 weeks, assessed using multifrequency bioimpedance analysis. Secondary endpoints include changes in body weight, fat mass, muscle, and fat cross-sectional area on CT, muscle strength, appetite, quality of life, hormonal markers, nutritional indicators, and adverse events. This study aims to clarify the potential benefits of anamorelin in mitigating postoperative deterioration of body composition in patients with UGI cancer and to provide essential preliminary data to inform the design of future confirmatory trials.