Short-course Radiotherapy Combined With Chemotherapy and Pd-1 Inhibitor for Locally Advanced Colon Cancer(TORCH-C)

Study Overview
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Brief Summary
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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
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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.

Official Title
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Short-course Radiotherapy Combined With CAPOX and Pd-1 Inhibitor for Locally Advanced Colon Cancer: a Randomized, Prospective, Multicentre, Phase II Trial (TORCH-C)

Conditions
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Locally Advanced Colon Cancer

Intervention / Treatment
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* Drug: Serplulimab
* Radiation: short-term radiotherapy
* Drug: Oxaliplatin
* Drug: Capecitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: pathological confirmed adenocarcinoma clinical stage T4 and/or bulky nodes the distance from anal verge more than 15 cm without distance metastases age >=18 years old, female and male KPS >=70 without previous anti-cancer therapy or immunotherapy with good compliance signed the inform consent Exclusion Criteria: pregnancy or breast-feeding women history of other malignancies within 5 years serious medical illness, such as severe mental disorders, cardiac disease, uncontrolled infection, etc. immunodeficiency disease or long-term using of immunosuppressive agents 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 allergic to any component of the therapy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: short-course radiotherapy and immunotherapy<br>A total of 60 patients will receive 5*5Gy short-course radiotherapy, followed by 4 cycles of CAPOX chemotherapy and PD-1 antibody, finally receive the surgery. | Drug: Serplulimab<br>* Serplulimab 300mg, d1, q3w<br>Radiation: short-term radiotherapy<br>* radiation: 25Gy/5Fx<br>* Other names: Shor-course radiotherapy: 25Gy/5Fx;Drug: Oxaliplatin<br>* 130mg/m2 d1 q3w<br>Drug: Capecitabine<br>* 1000mg/m2 d1-14 q3w<br>* Other names: Xeloda;|
| Active Comparator: chemotherapy<br>A total of 60 patients will receive 4 cycles of CAPOX chemotherapy ,then receive the surgery. | Drug: Oxaliplatin<br>* 130mg/m2 d1 q3w<br>Drug: Capecitabine<br>* 1000mg/m2 d1-14 q3w<br>* Other names: Xeloda;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pCR | pCR was defined as the absence, from surgical samples, of malignant cells in the primary site and regional lymph nodes | The pCR rate will be evaluated after surgery, an average of 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| R0 resection rate | R0 resection refers to the complete removal of the tumor in the operation with microscopically negative margins | The R0 resection rate will be evaluated after surgery, an average of 4 weeks | 
| 3 year overall survival rate | Rate of 3 years overall survival | From date of randomization until the date of death from any cause, assessed up to 3 years | 
| 3 year disease free survival rate | Rate of 3 years disease free survival | 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. | 
| Grade 3-4 adverse effects rate | Rate of chemotherapy, radiotherapy and immunotherapy related severe adverse events | From date of randomization until the date of death from any cause, assessed up to 5 years | 
| 3 year local recurrence free survival rate | Rate of 3 years local recurrence free survival | From date of randomization until the date of first documented local-regional failure, assessed up to 3 years | 
| Surgical complications | Rate of surgical complications, such as intraoperative hemorrhage, anastomotic leakage, intestinal obstruction, etc. | 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 |