The Combination of Immunotherapy and Neoadjuvant Chemoradiotherapy in MSI-H Locally Advanced Rectal Cancer

Study Overview
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Brief Summary
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The study evaluates the addition of immunotherapy of PD-1 antibody in neoadjuvant chemoradiotherapy in microsatellite stability-high (MSI-H) locally advanced rectal cancer (LARC). A total of 50 MSI-H LARC patients will receive 2 cycles of PD-1 antibody, followed by capecitabine plus irinotecan radiosensitized neoadjuvant chemoradiotherapy, and another 3 cycles of PD-1 antibody, finally received the total mesorectal excision (TME) and 6 cycles of adjuvant chemotherapy of XELOX. The tumor response grade, adverse effects and long-term prognosis will be analyzed.

Official Title
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A Phase II Trial of Immunotherapy Combined With Neoadjuvant Chemoradiotherapy in Microsatellite Instability-High Locally Advanced Rectal Cancer

Conditions
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Locally Advanced Rectal Cancer

Intervention / Treatment
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* Drug: PD-1 antibody
* Drug: Capecitabine
* Drug: Irinotecan
* Radiation: Neoadjuvant Radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: pathological confirmed adenocarcinoma clinical stage T3-4 and/or N+ the distance from anal verge less than 12 cm without distance metastases age 18-70 years old, female and male KPS >=70 UGT1A1*28 6/6 or 6/7 the MSI status is MSI-H or d-MMR 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 DPD deficiency UGT1A1*28 7/7 the MSI status is MSS or p-MMR allergic to any component of the therapy

Ages Eligible for Study
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Minimum Age: 15 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 50 MSI-H LARC patients will receive 2 cycles of PD-1 antibody, followed by capecitabine plus irinotecan radiosensitized neoadjuvant chemoradiotherapy, and another 3 cycles of PD-1 antibody, finally received the total mesorectal excision (TME) and 6 cycles of adjuvant chemotherapy of XELOX. | Drug: PD-1 antibody<br>* Before neo-CRT: 2 cycles of PD-1 antibody After neo-CRT: 3 cycles of PD-1 antibody<br>Drug: Capecitabine<br>* During neo-CRT: 625mg/m2 bid Monday-Friday per week<br>* Other names: Xeloda;Drug: Irinotecan<br>* During neo-CRT: 80mg/m2 qw (UGT1A1*28 6/6) or 65mg/m2 qw (UGT1A1*28 6/7)<br>Radiation: Neoadjuvant Radiotherapy<br>* IMRT DT: 50Gy/25Fx<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathologic Complete Response Rate | Pathologic Complete Response Rate | The pathologic complete response rate was evaluated after surgery, which was scheduled 7-8 weeks after the end of chemoradiotherapy. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease free 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 36 months. | 
| Local recurrence free survival | 3 year local recurrence free survival rate | From date of randomization until the date of first documented pelvic failure, assessed up to 36 months. | 
| Overall survival | 3 year overall survival rate | From date of randomization until the date of death from any cause, assessed up to 36 months. | 
| Adverse effects | Chemoradiation-related or immunotherapy-related adverse events | From date of randomization until the date of death from any cause, assessed up to 5 years | 
| Surgical complications | Surgical complications, such as intraoperative hemorrhage, anastomotic leakage, intestinal obstruction, etc. | The surgery was scheduled 7-8 weeks after the end of chemoradiotherapy. And the surgical complications were assessed up to 5 years from the surgery. | 
| Performance Status (Zubrod-ECOG-WHO method), range 0-5. The higher scores mean a worse quality of life. | Quality of life will be evaluated | From date of randomization until the date of death from any cause, assessed up to 10 years | 
| Karnofsky Performance Status, range 0-100. The higher scores mean a better quality of life. | Quality of life will be evaluated | From date of randomization until the date of death from any cause, assessed up to 10 years | 
| Quality of Life Scale, range 0-60. It evaluates the quality of life from 12 aspects, including appetite, mental status, sleep quality, fatigue, etc. The higher scores mean a better quality of life. | Quality of life will be evaluated | From date of randomization until the date of death from any cause, assessed up to 10 years |