Effect of Omega-3 Fatty Acids on PD-1 Inhibitor Therapy in Advanced Esophageal Cancer (ESO-Shanghai28): A Phase II Randomized Controlled Trial
This is a randomized, double-blind, placebo-controlled phase II clinical trial designed to evaluate whether adding omega-3 fatty acids improves outcomes in adult patients with recurrent or metastatic esophageal cancer receiving PD-1 inhibitor therapy. The main questions are: Compared with placebo, does omega-3 (EPA+DHA) increase the longitudinal change in skeletal muscle index (ΔSMI) over 6 months? Does it improve clinical outcomes and favorably modulate immune and metabolic biomarkers as well as patient-reported outcomes ? Participants will be randomized 1:1 to: Intervention: Standard PD-1 therapy plus oral omega-3 (EPA 2.5 g + DHA 1.25 g per day) for 6 months. Control: Standard PD-1 therapy plus matching placebo for 6 months. Participants will attend study visits at baseline, 3 months, and 6 months (then every 3 months up to 2 years), undergo body composition and functional assessments, blood sampling, and questionnaires, and have treatment adherence assessed per protocol. Pre-specified exploratory biomarker analyses will be conducted to support mechanism research.
• PD-1 inhibitor naïve, or prior PD-1 stopped \>3 months with subsequent progression (not primary PD-1 resistance).
• Adequate organ function per protocol (hematologic, hepatic, renal). Women of childbearing potential: negative pregnancy test and agree to effective contraception.
• Signed informed consent.