Long-course Chemoradiotherapy or Short-course Radiotherapy Combined With CAPOX, PD-1antibody, and COX-2 Inhibitor for MSS Locally Advanced Rectal Cancer (SERRAC)

Not Applicable

Recruiting

• Conditions: Locally Advanced Rectal Cancer; Neoadjuvant Therapy
• Interventions: Radiation: Long-course radiotherapy; Drug: Oxaliplatin; Drug: Capecitabine; Drug: Celecoxib; Radiation: Short-course radiotherapy; Drug: Serplulimab

• Registration Number: NCT07150949
• Lead Sponsor: Fudan University

Brief Summary

SERRAC is a prospective, multicentre, randomized phase II trial. 138 LARC (T3-4/N+M0, distance from anal verge ≤10cm) patients will be treated with neoadjuvant therapy and assigned to Group A and Group B (1:1). Group 1 receives LCRT (50Gy/25Fx) followed by 3 cycles of CAPOX.Group 2 receives SCRT (25Gy/5Fx) followed by 4 cycles of capecitabine plus oxaliplatin (CAPOX) chemotherapy and PD-1 antibody. The COX2 inhibitor celecoxib 200 mg was started orally twice a day during chemotherapy until the end of neoadjuvant treatment.TME surgery is scheduled after TNT while a watch and wait (W\&W) option can be applied to patients achieving clinical complete response (cCR). The primary endpoint is complete response (CR, pathological complete response \[pCR\] plus cCR) rate. The secondary endpoints include the grade 3-4 acute adverse effects (AE) rate, anal preservation rate, 3-year DFS rate, etc.

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-08
• Study First Submitted: 2025-08-27
• Study First Submitted QC: 2025-08-27
• Last Update Submitted: 2025-08-27
• Study Start: 2025-08-28
• Study First Posted: 2025-09-02
• Last Update Posted: 2025-09-02
• Primary Completion: 2027-08-31
• Study Completion: 2028-08-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 138

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Long-course Radiotherapy plus chemotherapy group	Long-course radiotherapy	-
Long-course Radiotherapy plus chemotherapy group	Oxaliplatin	-
Long-course Radiotherapy plus chemotherapy group	Capecitabine	-
Long-course Radiotherapy plus chemotherapy group	Celecoxib	-
Long-course Radiotherapy plus chemotherapy group	Serplulimab	-
Short-course Radiotherapy plus immunochemotherapy group	Oxaliplatin	-
Short-course Radiotherapy plus immunochemotherapy group	Capecitabine	-
Short-course Radiotherapy plus immunochemotherapy group	Celecoxib	-
Short-course Radiotherapy plus immunochemotherapy group	Short-course radiotherapy	-
Short-course Radiotherapy plus immunochemotherapy group	Serplulimab	-

Primary Outcome Measures

Name	Time	Method
Complete response (CR) rate	1 month after the surgery or the decision of W&W	Rate of complete response (CR), including the rate of pathologic complete response (pCR) after surgery and the rate of cCR with W\&W strategy.

Secondary Outcome Measures

Name	Time	Method
Grade 3-4 adverse effects rate	From date of randomization until 3 months after the completion neoadjuvant therapy	Rate of chemotherapy, radiotherapy and immunotherapy related adverse events
3 year anal preservation rate	From date of randomization until the date of or date of death from any cause, whichever came first, assessed up to 36 months.	3 year anal preservation rate
3 year disease free survival rate	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months.	Rate of 3 year disease free survival
3 year local recurrence free survival rate	From date of randomization until the date of first documented pelvic failure, assessed up to 36 months.	Rate of 3 year local recurrence free survival
3 year overall survival rate	From date of randomization until the date of death from any cause, assessed up to 36 months.	Rate of 3 year overall survival
Rate of surgical complications	The surgical complications were assessed within 3 months after the surgery.	Rate of surgical complications, such as intraoperative hemorrhage, anastomotic leakage, intestinal obstruction, etc.

Trial Locations

Locations (1)

Fudan University Shanghai Cancer Center; 🇨🇳 Shanghai, Shanghai Municipality, China