ARISTOTLE — Addition of Irinotecan to Preoperative Chemoradiotherapy for Locally Advanced Rectal Cancer

Phase 3 · 2026 · Colorectal Cancer

Design

Open-label randomized phase 3 trial: preoperative chemoradiotherapy (45 Gy in 25 fractions + capecitabine) versus the same CRT backbone plus weekly irinotecan, followed by total mesorectal excision.

Population

MRI-defined high-risk locally advanced rectal adenocarcinoma (T3c/d, T4, N2, or EMVI-positive on staging MRI).

Primary Endpoint

disease-free survival (DFS)

Key Result

Adding irinotecan to preoperative capecitabine-based CRT did not improve disease-free survival (HR 0.91, 95% CI 0.68–1.23; p=0.54) at 78-month median follow-up, while significantly increasing grade ≥3 toxicity.

Guideline Impact

Confirms standard capecitabine-based preoperative CRT without irinotecan intensification for MRI-defined high-risk locally advanced rectal cancer