Toripalimab Combined With Neoadjuvant Chemoradiotherapy as First-line Treatment for Locally Advanced，High-Risk，MSS Rectal Cancer

Study Overview
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Brief Summary
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This is a single arm, open-label, prospective clinical trial to evaluate the combination of neoadjuvant short-course radiotherapy and toripalimab (PD-1 antibody) for locally advanced rectal cancer (LARC) patients with high risk factors. A total of 53patients will be enrolled in this trial to receive 5*5Gy short-course radiotherapy, followed by 4 cycles of CAPOX chemotherapy and PD-1 antibody. Then they will receive the TME surgery and another 2 cycles of CAPOX chemotherapy. The primary end point is the rate of pathological complete response (pCR). The long-term prognosis and adverse effects will also be evaluated and analyzed.

Official Title
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Toripalimab Combined With Neoadjuvant Chemoradiotherapy as First-line Treatment for Locally Advanced，High-Risk，MSS Rectal Cancer

Conditions
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Locally Advanced, High-Risk, Rectal Cancer, MSS

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-75 years old, female and male; Pathological confirmed MSS or pMMR rectal adenocarcinoma; Clinical stage T3-4 (AJCC 8th) and at least with one high risk factor（CRM+ or EMVI+ or lateral lymph nodes+）; No previous chemotherapy, radiotherapy, immunotherapy or other anti-tumor treatment; Adequate organ function defined at baseline as: ANC ≥1.5××109/L，PLt ≥100×109 /L，Hb ≥90 g/L，15×109 /L≥WBC≥4×109 /L; TBIL ≤1.5×ULN, ALT ≤1.5ULN, AST ≤1.5ULN, BUN and Cr ≤1.5×ULN or Ccr 60ml/min (Cockcroft-Gault formula);INR ≤1.5×ULN or PT ≤1.5×ULN (when patient didn't accept anticoagulant therapy); Women of childbearing age must have taken reliable contraceptive measures or have a pregnancy test (serum or urine) within 7 days prior to enrollment and the results are negative; Exclusion Criteria: Pathological confirmed rectal squamous cell carcinoma; History of other uncured malignancies within 5 years; Allergic to any component of chemotherapy or immunotherapy; History of any active, known, or suspected autoimmune disease, including but not limited to myasthenia gravis,Myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis,Inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener granulation Swollen disease, Sjogren's syndrome, Guillain-Barre syndrome, multiple sclerosis, vasculitis or Glomerulonephritis. With congenital or acquired immunodeficiency (such as those with HIV infection), active hepatitis B or hepatitis C;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: short-course radiotherapy plus chemotherapy and immunotherapy<br>A total of 53 patients receive 5*5Gy short-course radiotherapy, followed by 4 cycles of CAPOX chemotherapy and PD-1 antibody, finally receive the TME surgery and another 2 cycles of CAPOX chemotherapy. | Drug: Toripalimab<br>* Toripalimab 240mg,d1,q3w<br>Radiation: short-term radiotherapy<br>* 25Gy/5Fx<br>* Other names: shor-course radiotherapy;Drug: Oxaliplatin<br>* 135mg/m2 d1 q3w<br>Drug: Capecitabine<br>* 1200mg/m2 d1-14 q3w<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pCR rate | Pathologic complete response rate | The TME surgery will be recommended after the neoadjuvant therapy. The pCR rate is evaluated after surgery. Assessed up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 3-year ORR | 3-year objective response rate | Assessed up to 3 years | 
| 3-year DCR | 3-year disease control rate | Assessed up to 3 years | 
| 3-year OS | 3-year overall survival rate | Assessed up to 3 years | 
| AE | adverse event | Assessed up to 3 years | 
| SAE | Serious Adverse Event | Assessed up to 3 years |