Modified Long-Course Radiotherapy Followed by Chemotherapy and PD-1 Inhibitor for MSS/pMMR High-risk Mid/Low LARC (MODIFI-RC-I)

The goal of this clinical trial is to evaluate whether a total neoadjuvant therapy (TNT) regimen combining long-course chemoradiotherapy, sequential chemotherapy, and PD-1 inhibitor can improve response rates, enhance tolerability, and improve prognosis in patients with locally advanced, microsatellite-stable (MSS) rectal cancer. The main questions it aims to answer are: Does this TNT approach improve complete response (CR) rates? How does selective reduction of clinical target volume (CTV) to S2/S3 level compare with conventional CTV irradiation in terms of efficacy and safety? Researchers will compare a selective CTV reduction group and a conventional CTV irradiation group to assess differences in treatment outcomes, including complete response, tumor regression grading (TRG), organ preservation, R0 resection rates, and long-term survival. Participants will: Receive long-course chemoradiotherapy with either conventional or reduced CTV irradiation. Undergo sequential chemotherapy. Receive PD-1 inhibitor treatment. Be monitored for safety, tumor regression, and long-term survival outcomes.

NCT Number	NCT06923345
Lead Sponsor	Sixth Affiliated Hospital, Sun Yat-sen University
Conditions	Rectal Cancer, Neoadjuvant Therapies, Immune Checkpoint Therapy, Radiotherapy
Enrollment	80 participants
Start Date	2025-03-31
Primary Completion	2027-12-31 (estimated)
Study Completion	2028-12-31 (estimated)
Updated on ClinicalTrials.gov	2025-04-18