The Combination of Immunotherapy and Neoadjuvant Short-course Radiotherapy in Early Rectal Cancer (TORCH-E）

Study Overview
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Brief Summary
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The study evaluates the combination of immunotherapy of PD-1 antibody and neoadjuvant short-course radiotherapy in early low rectal cancer. A total of 34 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 local excision(TEM) or total mesorectal excision (TME). The rate of complete response (CR, pCR + sustained cCR for ≥ 1 year), Organ retention rate, long-term prognosis, and adverse effects will be analyzed.

Official Title
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A Prospective Phase II Trial of Immunotherapy Combined With Short-course Radiotherapy in Early Low Rectal Cancer

Conditions
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Early Low Rectal Cancer

Intervention / Treatment
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* Drug: PD-1 antibody
* Drug: Capecitabine
* Drug: Oxaliplatin
* Radiation: Short-course radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age 18-70 years old, female and male pathological confirmed adenocarcinoma clinical stage T1-3bN0, tumor maximum diameter less than 4cm the distance from anal verge less than 5 cm without distance metastases KPS >=70 with good compliance microsatellite repair status is MSS/pMMR without previous anti-cancer therapy or immunotherapy signed the inform consent Exclusion Criteria: pregnancy or breast-feeding women pathological confirmed signet ring cell carcinoma clinical stage T1N0 and can be resected locally 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 DPD deficiency allergic to any component of the therapy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Treatment Arm<br>A total of 34 patients will receive 5*5Gy short-course radiotherapy, followed by 4 cycles of CAPOX chemotherapy and PD-1 antibody, finally receive the TEM or TME surgery. | Drug: PD-1 antibody<br>* PD-1 antibody (Toripalimab): 240mg d1 q3w<br>* Other names: Toripalimab;Drug: Capecitabine<br>* Capecitabine: 1000mg/m2 d1-14 q3w<br>* Other names: Xeloda;Drug: Oxaliplatin<br>* Oxaliplatin: 130mg/m2 d1 q3w<br>Radiation: Short-course radiotherapy<br>* Shor-course radiotherapy: 25Gy/5Fx<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| complete response (CR) rate | Rate of complete response (CR), including pathologic complete response (pCR) and sustained cCR for ≥ 1 year. | The status of cCR will be evaluated after the completion of neoadjuvant therapy. The pCR rate will be evaluated after surgery. The W&W patients with cCR for ≥ 1 year will be included into the CR rate caluculation. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Organ preservation rate | Rate of cCR or near-cCR after neoadjuvant therapy underwent nonsurgical treatment or radical resection | from date of receiving neoadjuvant therapy, assessed up to 2 years | 
| Grade 3-4 adverse effects rate | Rate of chemotherapy, radiotherapy and immunotherapy related adverse events | From date of initiation of treatment until the date of death from any cause, assessed up to 5 years | 
| 3 year disease free survival rate | Rate of 3 year disease free survival | From date of initiation of treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months. | 
| 3 year local recurrence free survival rate | Rate of 3 year local recurrence free survival | From date of initiation of treatment until the date of first documented pelvic failure, assessed up to 36 months. | 
| 3 year overall survival rate | Rate of 3 year overall survival | From date of initiation of treatment until the date of death from any cause, assessed up to 36 months. | 
| 10 year Quality of Life | Quality of life will be evaluated using EORTC QLQ-C30, EORTC QLQ-CR29, LARS score and Wexner score. | From date of initiation of treatment until the date of death from any cause, assessed up to 10 years |