NCT06958419

Node-Sparing Short-Course Radiotherapy Plus Chemotherapy, Bevacizumab and PD-1 Inhibitor in Metastatic pMMR/MSS Colorectal Cancer (MODIFI-CRC)

Node-Sparing Short-Course Radiotherapy Followed by First-Line Chemotherapy Plus Bevacizumab and PD-1 Inhibitor Versus Chemotherapy Plus Bevacizumab Alone in Metastatic pMMR/MSS Colorectal Cancer: A Randomized, Phase II/III Trial (MODIFI-CRC)

• Status: Recruiting
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 286 (estimated)
• Sponsor: Sixth Affiliated Hospital, Sun Yat-sen University · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

The current standard first-line treatment for metastatic colorectal cancer is chemotherapy combined with targeted therapy, yet the prognosis remains poor. Although combining immunotherapy, anti-angiogenic agents, and chemotherapy has shown some efficacy in MSS/pMMR metastatic patients, progression-free survival (PFS) remains suboptimal. Radiotherapy-particularly high-dose radiotherapy-can enhance tumor antigen release and potentially improve the response of MSS/pMMR colorectal cancer to PD-1 inhibitors. Tumor-draining lymph nodes (TDLNs) are key sites for PD-1-mediated anti-tumor activity, but radiation-induced damage and fibrosis may impair their immune function. Prior studies have reported a remarkable pathologic complete response (pCR) rate of 77.8% using node-sparing radiotherapy in locally advanced rectal cancer. This phase II/III study aims to evaluate whether node-sparing modified short-course radiotherapy combined with chemotherapy, bevacizumab, and PD-1 blockade can improve objective response rate (ORR) in phase II and progression-free survival (PFS) in phase III, together with treatment tolerance, and overall prognosis in patients with pMMR/MSS metastatic colorectal cancer.

Conditions

• Immune Checkpoint Therapy
• Radiotherapy
• Metastatic Colorectal Cancer (CRC)

Interventions

Type	Name	Description
COMBINATION_PRODUCT	Node-Sparing Radiotherapy plus first-line therapy	Patients will receive node-sparing modified short-course radiotherapy, followed by 8 cycles of FOLFOX chemotherapy combined with bevacizumab and a PD-1 inhibitor. After induction therapy, patients will continue with maintenance therapy using bevacizumab, PD-1 inhibitor, and 5-fluorouracil (5-FU), administered every 2 weeks (Q2W).
COMBINATION_PRODUCT	First-line treatment	Patients will receive 8 cycles of FOLFOX chemotherapy combined with bevacizumab, followed by maintenance therapy with bevacizumab and 5-fluorouracil (5-FU), administered every 2 weeks (Q2W).

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