Long-course chemoradiation or short-course radiation with CAPOX, PD-1 antibody, and celecoxib for MSS locally advanced rectal cancer

A Prospective Randomized Phase II Trial of Long-Course Chemoradiotherapy or Short-Course Radiotherapy Combined With CAPOX, PD-1 Antibody, and a COX-2 Inhibitor for Microsatellite Stable Locally Advanced Rectal Cancer (SERRAC)

This trial tests whether adding a PD‑1 immune drug and the anti‑inflammatory celecoxib to standard CAPOX chemotherapy with either long- or short-course radiotherapy helps people with MSS locally advanced rectal cancer achieve a complete response before surgery.

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
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT07150949 on ClinicalTrials.gov

What this trial studies

This is a randomized phase II trial enrolling 138 patients with T3-4/N+ M0 rectal adenocarcinoma located within 10 cm of the anal verge and confirmed MSS/pMMR. Participants are assigned 1:1 to long-course chemoradiotherapy (LCRT) followed by three cycles of CAPOX, or short-course radiotherapy (SCRT) followed by four cycles of CAPOX combined with a PD‑1 antibody; all patients receive oral celecoxib during chemotherapy. Total mesorectal excision (TME) is planned after total neoadjuvant therapy, while patients achieving a clinical complete response may be offered a watch-and-wait approach. The primary endpoint is complete response rate (pathologic plus clinical complete responses), with secondary endpoints including grade 3–4 acute adverse event rate, anal preservation rate, and 3-year disease-free survival.

Who should consider this trial

Good fit: Ideal candidates are adults 18–75 with biopsy-proven T3-4/N+ M0 rectal adenocarcinoma within 10 cm of the anus, MSS/pMMR status, Karnofsky score ≥70, no prior anti-cancer or immunotherapy, and able to comply with the protocol and give informed consent.

Not a fit: Patients with distant metastases, MSI-high/MMR-deficient tumors, prior radiotherapy or systemic cancer therapy, significant cardiac/renal/hepatic dysfunction, pregnancy, or recent other malignancies are unlikely to benefit or are excluded.

Why it matters

Potential benefit: If successful, this approach could raise complete response rates and increase the chance of avoiding surgery or preserving the anus while improving longer-term disease control.

How similar studies have performed: Total neoadjuvant therapy combining radiotherapy and chemotherapy with immune checkpoint inhibitors has shown promising early results in rectal cancer, but adding a COX-2 inhibitor like celecoxib is a more novel approach with limited prior validation.

Eligibility criteria

Inclusion Criteria:

1. Age 18-75 years, gender not limited
2. Pathologically confirmed rectal adenocarcinoma
3. ≤10 cm from the anus
4. Baseline stage T3-4/N+
5. No distant metastasis
6. MSI/MMR status MSS/pMMR
7. Karnofsky performance status score ≥70
8. No prior chemotherapy or other anti-cancer treatment prior to enrollment
9. No prior immunotherapy prior to enrollment
10. Ability to comply with the study protocol
11. Written informed consent

Exclusion Criteria:

1. Pregnancy or breast-feeding women;
2. Known history of other malignancies within 5 years;
3. Known history of previous anti-tumor treatment, including radiotherapy, chemotherapy, immune checkpoint inhibitors, T cell-related therapy, etc;
4. Known history of severe neurological or mental illness (such as schizophrenia, dementia or epilepsy);
5. Current severe cardiac disease (cardiac dysfunction and arrhythmia), renal dysfunction and liver dysfunction;
6. Acute cardiac infarction or cerebral ischemic stroke occurred within 6 months before recruitment;
7. Uncontrolled infection which needs systemic therapy;
8. Active autoimmune disease or immunodeficiencies, known history of organ transplantation or systematic use of immunosuppressive agents;
9. Known history of human immunodeficiency virus (HIV) infection (i.e., HIV 1 to 2 antibody positive), active syphilis infection, active pulmonary tuberculosis infection
10. Allergic to any component of the therapy.

Where this trial is running

Shanghai, Shanghai Municipality

• Fudan University Shanghai Cancer Center — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Principal investigator: Zhen Zhang, M.D, PH.D — Fudan University
• Study coordinator: Zhen Zhang, M.D, PH.D

Conditions Locally Advanced Rectal Cancer; Neoadjuvant Therapy