NCT07230639

Node-Sparing Hypofractionated Radiotherapy Plus Chemotherapy and PD-1 Inhibitor in pMMR/MSS High-Risk Locally Advanced Colon Cancer: A Prospective, Randomized, Phase II Trial

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 52 (estimated)
• Sponsor: Sixth Affiliated Hospital, Sun Yat-sen University · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

Most colorectal cancers are microsatellite stable (MSS) or mismatch repair-proficient (pMMR) subtypes, which show limited efficacy to PD-1 inhibitors. Radiotherapy can enhance the release of tumor-associated antigens, thereby improving the responsiveness of pMMR/MSS colorectal cancers to PD-1 blockade. Tumor-draining lymph nodes (TDLNs) are critical sites where PD-1 inhibitors exert their antitumor effects; however, previous studies have reported that direct radiation-induced damage and fibrosis may impair lymphatic drainage and antitumor immunity. Early reports have demonstrated a remarkable pathological complete response (pCR) rate of 77.8% with lymph node-sparing short-course radiotherapy (25 Gy in 5 fractions) in locally advanced rectal cancer. In metastatic colorectal cancer, single-fraction high-dose irradiation (6-8 Gy) has been shown to induce robust abscopal effects. Based on these findings, our study aims to evaluate whether lymph node-sparing hypofractionated radiotherapy (25 Gy/5F or 24 Gy/4F) followed sequentially by chemotherapy and PD-1 blockade can increase the pCR rate, improve tolerability, and ultimately enhance outcomes in patients with pMMR/MSS high-risk locally advanced colon cancer.

Conditions

• Neoadjuvant Therapies
• Immune Checkpoint Therapy
• Radiotherapy

Interventions

Type	Name	Description
COMBINATION_PRODUCT	Node-Sparing Radiotherapy(25Gy/5F) plus Chemotherapy and PD-1 inhibitor	Patients will receive node-sparing modified short-course radiotherapy(25Gy/5F), followed by 4 cycles of CAPOX chemotherapy combined with a PD-1 inhibitor. After neoadjuvant treatment, patients will undergo surgery.
COMBINATION_PRODUCT	Node-Sparing Radiotherapy(24Gy/4F) plus Chemotherapy and PD-1 inhibitor	Patients will receive node-sparing modified short-course radiotherapy(24Gy/4F), followed by 4 cycles of CAPOX chemotherapy combined with a PD-1 inhibitor. After neoadjuvant treatment, patients will undergo surgery.

Timeline

• Start date: 2025-08-30
• Primary completion: 2030-08-29
• Completion: 2031-12-31
• First posted: 2025-11-17
• Last updated: 2025-12-26

Locations

1 site across 1 country: China