NCT06908031

SCRT + mFOLFOX6 + PD-1 Antibody + Targeted Therapy for HIgh-Risk pMMR/MSS Rectal Cancer

Short-Course Radiotherapy Combined With mFOLFOX6, PD-1 Antibody and Cetuximab (for RAS/BRAF Wild-Type)/Bevacizumab (for RAS/BRAF Mutant) in High-Risk pMMR/MSS Rectal Adenocarcinoma: a Prospective, Multicenter Phase II Study

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 49 (estimated)
• Sponsor: Sixth Affiliated Hospital, Sun Yat-sen University · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

To explore the efficacy and safety of short-course radiotherapy combined with mFOLFOX6, PD-1 monoclonal antibody and cetuximab (for RAS/BRAF Wild-Type)/bevacizumab (for RAS/BRAF Mutant) in High-Risk pMMR/MSS Rectal Adenocarcinoma through a prospective study, providing high-level evidence-based medical evidence for the use in the treatment of high-risk rectal cancer.

Detailed description

Patients with locally advanced rectal cancer (LARC) who have high-risk factors, such as low rectal cancer, clinical stage T4b, positive mesorectal fascia (MRF), and positive extramural vascular invasion (EMVI), are at extremely high risk of distant metastasis. For these LARC patients with high-risk factors, the pathological complete response (PCR) rate with neoadjuvant chemotherapy alone is relatively low, ranging from 4.3% to 13.3%. Therefore, the use of a more potent comprehensive neoadjuvant treatment regimen, including concurrent chemoradiotherapy combined with targeted therapy and immunotherapy, may offer greater benefits to these patients. For patients with high-risk LARC, this study aims to explore whether the combination of short-course radiotherapy, mFOLFOX6, PD-1 monoclonal antibody and cetuximab (for RAS/BRAF Wild-Type)/bevacizumab (for RAS/BRAF Mutant) can improve the pathological responce rate, and achieve better long-term survival benefits. The study will investigate the efficacy and safety of short-course radiotherapy, mFOLFOX6, PD-1 monoclonal antibody and cetuximab (for RAS/BRAF Wild-Type)/bevacizumab (for RAS/BRAF Mutant) for high-risk LARC in treating liver metastases, with the goal of providing high-level evidence-based medical evidence for the use of local hypofractionated radiotherapy combined with PD-1 monoclonal antibody in the treatment of unresectable colorectal cancer liver metastasis. This is a prospective, open-label, multicenter, single-arm, Phase II study. Patients with high-risk LARC will be eligible for enrollment. Enrolled patients will receive neoadjuvant treatment phase includes short-course radiotherapy (SCRT) combined with four cycles of the mFOLFOX6 regimen, PD-1 monoclonal antibody, and molecularly targeted drugs (selected based on RAS status; patients with RAS/BRAF wild-type receive cetuximab, while those with RAS/BRAF mutations receive bevacizumab). After completing the first cycle of mFOLFOX6 chemotherapy combined with targeted and immune therapy, patients undergo SCRT at a dose of 5Gy × 5 fractions. At least 7 days after the completion of radiotherapy, patients continue with three additional cycles of mFOLFOX6 chemotherapy combined with PD-1 monoclonal antibody and targeted drugs (bevacizumab is not used in the last cycle of the bevacizumab group). Surgery is performed 8-10 weeks after the completion of SCRT. If pelvic MRI indicates clinical complete response (CCR) and N0, local excision (local excision, LE) will be performed. If pelvic MRI suggests clinical restaging as T1N0M0, LE surgery will be carried out. Otherwise, total mesorectal excision (TME) will be performed. The decision regarding adjuvant chemotherapy after surgery will be made by the attending physician.

Conditions

• Rectal Adenocarcinoma
• High-Risk Cancer
• MSS

Interventions

Type	Name	Description
RADIATION	Short-Course Radiotherapy	Patients undergo SCRT at a dose of 5Gy × 5 fractions
DRUG	PD-1 monoclonal antibody	Patients complete immune therapy with PD-1 monoclonal antibody for 4 cycles.
DRUG	mFOLFOX6 regimen	Patients complete chemotherapy with mFOLFOX6 regimen for 4 cycles.
DRUG	Cetuximab	Patients with RAS/BRAF wild-type receive targeting therapy with Cetuximab for 4 cycles.
DRUG	Bevacizumab	Patients with RAS/BRAF mutations receive targeting therapy with Bevacizumab for 3 cycles. (Bevacizumab is not used in the last cycle of the bevacizumab group)
PROCEDURE	Surgical resection	Surgery either local excition or total mesorectal excision is performed 8-10 weeks after the completion of short-course radiotherapy.

Timeline

• Start date: 2025-04-02
• Primary completion: 2027-04-01
• Completion: 2027-04-01
• First posted: 2025-04-03
• Last updated: 2025-05-14

Locations

1 site across 1 country: China