Serine/Glycine-Restricted Diet With Chemoradiotherapy for Rectal Cancer

This is a Phase Ib/II seamless, open‐label, randomized controlled trial evaluating thesafety and efficacy of a serine/glycine‐restricted diet combined with neoadjuvantchemoradiotherapy and immunotherapy in patients with locally advanced rectal cancer(LARC).The study consists of two phases. Phase Ib is a non‐randomized, single‐arm safety run‐inphase enrolling 6 patients, all of whom will receive the experimental regimen(serine/glycine‐restricted diet plus CAPOX chemotherapy, PD‐1 inhibitor, and short‐courseradiotherapy). The primary objective of Phase Ib is to assess safety, tolerability, anddietary compliance. If the safety criteria are met (≥3 grade diet‐related adverse eventrate ≤20% and compliance rate ≥70%), the study will proceed to Phase II.Phase II is a randomized, open‐label, parallel‐controlled phase in which 134 additionalpatients will be randomized in a 1:1 ratio to either the experimental group(serine/glycine‐restricted diet plus standard neoadjuvant chemoradiotherapy andimmunotherapy) or the control group (standard neoadjuvant chemoradiotherapy andimmunotherapy alone). The total enrollment is 140 patients (6 in Phase Ib + 134 in PhaseII).The primary endpoint is the complete response rate (pCR + cCR). Secondary endpointsinclude major pathological response (MPR) rate, R0 resection rate, mrTRG regressiongrade, event‐free survival (EFS), progression‐free survival (PFS), overall survival (OS),adverse event profile, changes in serum amino acid levels, quality of life (EORTCQLQ‐C30), and nutritional status. Exploratory endpoints include gut microbiome diversityand tumor immune microenvironment changes.