Comparing long-course chemoradiation versus short-course radiation plus CAPOX, a PD-1 blocker (serplulimab), and celecoxib for 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 trial will test whether adding CAPOX, the PD-1 drug serplulimab, and celecoxib to short-course radiotherapy works better than standard long-course chemoradiation for adults with MSS locally advanced rectal cancer.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 138 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Fudan University (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, serplulimab
• Locations: 5 sites (Fuzhou, Fujian and 4 other locations)
• Trial ID: NCT07154316 on ClinicalTrials.gov

What this trial studies

This randomized phase II trial enrolls adults with microsatellite-stable (MSS) locally advanced rectal adenocarcinoma to compare standard long-course chemoradiotherapy (50 Gy in 25 fractions with capecitabine) against short-course radiotherapy (25 Gy in 5 fractions) followed by CAPOX (capecitabine plus oxaliplatin), the PD-1 inhibitor serplulimab, and the COX-2 inhibitor celecoxib. The primary endpoint is combined complete response rate (pathologic complete response plus clinical complete response), with secondary endpoints including anal-preservation rate and three-year survival outcomes. The protocol also includes correlative studies to explore how the triple regimen alters the tumor microenvironment and immune response. Participants must be treatment-naïve for chemotherapy and immunotherapy and have tumors located ≤10 cm from the anal verge.

Who should consider this trial

Good fit: Ideal candidates are adults age 18–75 with pathologically confirmed MSS/pMMR locally advanced rectal adenocarcinoma (T3-4 and/or N+, tumor ≤10 cm from anal verge), no distant metastasis, KPS ≥70, and no prior chemotherapy or immunotherapy.

Not a fit: Patients with MSI-high/dMMR tumors, distant metastases, prior systemic therapy, poor performance status, pregnancy, or serious uncontrolled comorbidities are unlikely to benefit or are ineligible for this protocol.

Why it matters

Potential benefit: If successful, the combination approach could raise complete remission rates and increase the chance of preserving the anus while reducing recurrence.

How similar studies have performed: Short-course radiotherapy combined with chemotherapy and PD-1 blockade has shown encouraging early signals in rectal cancer, but adding a COX-2 inhibitor like celecoxib is a novel component that remains exploratory.

Eligibility criteria

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.

Where this trial is running

Fuzhou, Fujian and 4 other locations

• Fujian Provincial Cancer Hospital — Fuzhou, Fujian, China (Recruiting)
• Anyang Tumor Hospital — Anyang, Henan, China (Recruiting)
• The First Affiliated Hospital of Shandong First Medical University — Jinan, Shandong, China (Recruiting)
• Yunnan Cancer Hospital — Kunming, China (Recruiting)
• Fudan University Shanghai Cancer Center — Shanghai, China (Recruiting)

Study contacts

• Study coordinator: Dawei Li

Conditions Colorectal Cancer