Locally Advanced Colon Cancer
Conditions
Brief summary
The study evaluates the combination of immunotherapy of PD-1 antibody and chemotherapy and neoadjuvant short-course radiotherapy in locally advanced colon cancer (LACC). Patients are randomly assigned into two prospective groups: treatment group and observerment group. In treatment group, a total of 60 patients will receive 5\*5Gy short-course radiotherapy, followed by 4 cycles of capecitabine plus oxaliplatin (CAPOX) chemotherapy and PD-1 antibody, finally receive the surgery. In observerment group: a total of 60 patients will receive 4 cycles of CAPOX chemotherapy, then receive the surgery. The rate of pathologic complete response （pCR）, long-term prognosis and adverse effects will be analyzed.
Detailed description
This study is a prospective, randomized controlled, multicenter phase II study, with a design of superior efficacy，to compare the efficacy of neoadjuvant short-course radiotherapy combined with CapOX chemotherapy and PD-1 immunotherapy in locally advanced colon cancer. We will consecutively enrolled patients who were diagnosed with locally advanced colon cancer with T4 stage or bulky nodes. A total of 120 patients will be Randomized 1:1 to the treatment group and observerment group. In observerment group, patients will receive 4 cycles of CAPOX (Capecitabine: 1000mg/m2 d1-14 q3w; Oxaliplatin: 130mg/m2 d1 q3w)chemotherapy, then receive the surgery, followed by 4 cycles of CAPOX. In treatment group, patients will receive 5\*5Gy short-course radiotherapy, followed by 4 cycles of CAPOXand PD-1 antibody(Serplulimab,300mg d1 q3w), then receive the surgery,followed by 4 cycles of CAPOX.
Interventions
DRUGSerplulimab
Serplulimab 300mg, d1, q3w
RADIATIONshort-term radiotherapy
radiation: 25Gy/5Fx
DRUGOxaliplatin
130mg/m2 d1 q3w
DRUGCapecitabine
1000mg/m2 d1-14 q3w
Sponsors
Fudan University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. pathological confirmed adenocarcinoma 2. clinical stage T4 and/or bulky nodes 3. the distance from anal verge more than 15 cm 4. without distance metastases 5. age \>=18 years old, female and male 6. KPS \>=70 7. without previous anti-cancer therapy or immunotherapy 8. with good compliance 9. signed the inform consent
Exclusion criteria
1. pregnancy or breast-feeding women 2. history of other malignancies within 5 years 3. serious medical illness, such as severe mental disorders, cardiac disease, uncontrolled infection, etc. 4. immunodeficiency disease or long-term using of immunosuppressive agents 5. baseline blood and biochemical indicators do not meet the following criteria: neutrophils≥1.5×10\^9/L, Hb≥90g/L, PLT≥100×10\^9/L, ALT/AST ≤2.5 ULN, Cr≤ 1 ULN 6. allergic to any component of the therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| pCR | The pCR rate will be evaluated after surgery, an average of 4 weeks | pCR was defined as the absence, from surgical samples, of malignant cells in the primary site and regional lymph nodes |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 3 year overall survival rate | From date of randomization until the date of death from any cause, assessed up to 3 years | Rate of 3 years overall survival |
| 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 3 years. | Rate of 3 years disease free survival |
| R0 resection rate | The R0 resection rate will be evaluated after surgery, an average of 4 weeks | R0 resection refers to the complete removal of the tumor in the operation with microscopically negative margins |
| 3 year local recurrence free survival rate | From date of randomization until the date of first documented local-regional failure, assessed up to 3 years | Rate of 3 years local recurrence free survival |
| Surgical complications | The surgery was scheduled 2-4 weeks after the end of neoadjuvant therapy. And the surgical complications were assessed up to 5 years from the surgery | Rate of surgical complications, such as intraoperative hemorrhage, anastomotic leakage, intestinal obstruction, etc. |
| Grade 3-4 adverse effects rate | From date of randomization until the date of death from any cause, assessed up to 5 years | Rate of chemotherapy, radiotherapy and immunotherapy related severe adverse events |
Outcome results
None listed