Locally Advanced Rectal Cancer, Neoadjuvant Therapy
Conditions
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.
Interventions
RADIATIONLong-course radiotherapy
Long-course radiation: 50Gy/25Fx
DRUGOxaliplatin
Oxaliplatin: 130mg/m2 d1 q3w
DRUGCapecitabine
Xeloda
DRUGCelecoxib
celecoxib 200 mg orally twice a day
RADIATIONShort-course radiotherapy
Short-course radiotherapy: 25Gy/5Fx
DRUGSerplulimab
Serplulimab 300mg, d1, q3w
Sponsors
Fudan University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 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. |
| 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 |
Countries
China
Contacts
Primary ContactZhen Zhang, M.D, PH.D
Backup ContactYajie Chen, PH.D
Outcome results
None listed