Standard treatment for patients with proficient mismatch repair (pMMR) / microsatellite stable (MSS) locally advanced rectal cancer (LARC) consists primarily of neoadjuvant chemoradiotherapy followed by radical surgery. Several studies (including the UNION, STELLAR, TORCH, and SPRING-01 trials, etc) have demonstrated that the neoadjuvant strategy of short-course radiotherapy followed by chemotherapy combined with immunotherapy can improve pCR rate in patients with pMMR/MSS LARC, and might also provide higher organ preservation rates and long-term survival benefits. The study aims to explore the efficacy and safety of a TNT regimen comprising short-course radiotherapy combined with chemotherapy, cetuximab N01 (for patients with wild-type RAS/BRAF) or bevacizumab (for patients with mutant RAS/BRAF), and sintilimab in patients with high-risk LARC.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
60
SCRT: 25 Gy, 5 Gy × 5 fr. One week after completion of SCRT: 1. Patients with wild-type RAS/BRAF: mFOLFOX6: oxaliplatin 85 mg/m², leucovorin 400 mg/m², 5-fluorouracil 400 mg/m² IV bolus on Day 1; followed by 5-fluorouracil 2400 mg/m² continuous infusion over 46 hours, q2w; sintilimab 200 mg/m² IV infusion on Day 1, q3w; cetuximab N01 500 mg/m² IV infusion on Day 1, q2w; Combination therapy for 18 weeks (9 cycles of chemotherapy). 2. Patients with mutant RAS/BRAF: CAPOX: oxaliplatin 130 mg/m² IV ivgtt, D1; capecitabine 1000 mg/m² BID, po, D1-14, q3w, for 6 cycles; sintilimab 200 mg/m² ivgtt, D1, q3w, for 6 cycles; bevacizumab 7.5 mg/kg IV infusion on Day 1, q3w, for 5 cycles
China PLAGH
Beijing, China
Complete Response (CR)
CR = Pathological Complete Response (pCR) + Clinical Complete Response (cCR)
Time frame: Within 3 months after surgery
R0 resection rate
Proportion of patients achieving a margin-negative tumor removal
Time frame: Within 3 months after surgery
LER
Local Excision rate
Time frame: Within 3 months after surgery
ORR
Objective Response Rate of neoadjuvant therapy ( by RECIST 1.1)
Time frame: Around 6 months after recruitment
DCR
Disease Control Rate of neoadjuvant therapy (by RECIST 1.1)
Time frame: Around 6 months after recruitment
3y-EFS
3 years events-free survival
Time frame: Around 3 years after recruitment
3y-RFS
3 years recurrence-free Survival
Time frame: Around 3 years after recruitment
OS
Overall Survival
Time frame: Around 5 years after recruitment
Safety Measures
Incidence and grades of treatment related adverse events (by NCI-CTCAE 5.0) and surgery related safeties
Time frame: Within 3 months after surgery
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