NCT06958432

Node-Sparing Short-Course Radiotherapy Sequential Chemotherapy and PD-1 Inhibitor for Mid/Low pMMR/MSS Rectal Cancer (MODIFI-RC-II)

Node-Sparing Short-Course Radiotherapy Plus Sequential Chemotherapy and PD-1 Inhibitor for Mid/Low pMMR/MSS Rectal Cancer: An Open-Label, Randomized, Prospective Phase II/III Trial (MODIFI-RC-II)

• Status: Recruiting
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 430 (estimated)
• Sponsor: Sixth Affiliated Hospital, Sun Yat-sen University · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

Most rectal cancers are microsatellite stable (MSS) or mismatch repair-proficient (pMMR) and respond poorly to PD-1 inhibitors. Radiotherapy can enhance tumor antigen release and improve responsiveness to PD-1 blockade in MSS/pMMR rectal cancer. Tumor-draining lymph nodes (TDLNs) are critical sites for anti-tumor immune activation, but radiation-induced damage and fibrosis may impair lymphatic drainage and immune responses. Previous studies have reported a remarkable pathologic complete response (pCR) rate of 77.8% using node-sparing radiotherapy in locally advanced rectal cancer. This study aims to evaluate whether node-sparing short-course radiotherapy followed by sequential chemotherapy and PD-1 blockade can improve complete response rate in the phase II part and event-free survival in phase III part, together with sphincter preservation, treatment tolerance, and prognosis in patients with mid-low pMMR/MSS rectal cancer.

Conditions

• Rectal Cancer
• Neoadjuvant Therapies
• Immune Checkpoint Therapy
• Radiotherapy

Interventions

Type	Name	Description
COMBINATION_PRODUCT	Node-Sparing Radiotherapy plus Chemotherapy and PD-1 inhibitor	Patients will receive node-sparing modified short-course radiotherapy, followed by six cycles of CAPOX chemotherapy combined with a PD-1 inhibitor. After neoadjuvant treatment, patients will either undergo total mesorectal excision (TME) surgery or enter a watch-and-wait strategy based on clinical assessment.
COMBINATION_PRODUCT	Conventional Radiotherapy plus Chemotherapy and PD-1 inhibitor	Patients will receive conventional-target short-course radiotherapy, followed by six cycles of CAPOX chemotherapy. After neoadjuvant treatment, patients will either undergo TME surgery or enter a watch-and-wait strategy based on clinical assessment.

Timeline

• Start date: 2025-05-01
• Primary completion: 2030-12-31
• Completion: 2031-12-31
• First posted: 2025-05-06
• Last updated: 2025-08-07

Locations

1 site across 1 country: China