Phase II RCT of LCRT vs SCRT + CAPOX/PD-1i/COX-2i in MSS Locally Advanced Rectal Cancer

A Randomized Phase II Study of Long-term Chemoradiotherapy or Short-term Radiotherapy Combined With CAPOX, PD-1 Monoclonal Antibody and COX-2 Inhibitors in MSS Type Locally Advanced Rectal Cancer

This randomized phase II trial evaluates the efficacy of long-course chemoradiotherapy (50Gy/25Fx + capecitabine) versus short-course radiotherapy (25Gy/5Fx) combined with CAPOX（Capecitabine and Oxaliplatin）, PD-1 inhibitor (serplulimab), and COX-2 inhibitor (celecoxib) in MSS（MicroSatellite Stable） locally advanced rectal cancer, with primary endpoint of complete response rate (pCR+cCR)（Complete Remission） and secondary endpoints including anal preservation rate and 3-year survival outcomes, aiming to elucidate the immunomodulatory effects of triple therapy on tumor microenvironment.

Inclusion Criteria:

• Age 18-75 years, regardless of gender.
• Pathologically confirmed rectal adenocarcinoma.
• Tumor located ≤10 cm from the anal verge.
• Baseline stage T3-4 and/or N+ (locally advanced disease).
• No evidence of distant metastasis.
• Microsatellite stability (MSS) or proficient mismatch repair (pMMR).
• Karnofsky Performance Status (KPS) ≥70.
• No prior chemotherapy or any other anticancer therapy before enrollment.
• No prior immunotherapy.
• Able to comply with study protocol requirements throughout the study period.
• Signed written informed consent obtained prior to study participation.

Exclusion Criteria:

• Pregnant or lactating women.
• Individuals with a history of other malignant diseases within the past 5 years, excluding cured skin cancer and cervical carcinoma in situ.
• Individuals with a history of uncontrolled epilepsy, central nervous system diseases, or mental disorders, where the clinical severity (as judged by the investigator) may impair the ability to sign the informed consent form or affect compliance with oral medication.
• Clinically significant (i.e., active) heart disease, including symptomatic coronary heart disease, congestive heart failure of New York Heart Association (NYHA) class II or worse, severe arrhythmias requiring pharmacological intervention, or a history of myocardial infarction within the past 12 months.
• Individuals requiring immunosuppressive therapy for organ transplantation and those on long-term corticosteroid therapy.
• Individuals with autoimmune diseases.
• Individuals with severe, uncontrolled, recurrent infections or other severe, uncontrolled concurrent diseases.
• Baseline blood routine and biochemical parameters not meeting the following criteria: hemoglobin ≥90 g/L; absolute neutrophil count (ANC) ≥1.5×10⁹/L; platelets ≥100×10⁹/L; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5× upper limit of normal (ULN); alkaline phosphatase (ALP) ≤2.5×ULN; serum total bilirubin <1.5×ULN; serum creatinine <1×ULN; serum albumin ≥30 g/L.
• Individuals with known dihydropyrimidine dehydrogenase (DPD) deficiency. Individuals with a history of hypersensitivity to any component of the study medications.