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

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

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.

Inclusion Criteria:

1. pathological confirmed adenocarcinoma
2. clinical stage T3-4 and/or N+
3. the distance from anal verge less than 12 cm
4. without distance metastases
5. age 18-70 years old, female and male
6. KPS >=70
7. UGT1A1*28 6/6 or 6/7
8. the MSI status is MSI-H or d-MMR
9. without previous anti-cancer therapy or immunotherapy
10. with good compliance
11. 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. DPD deficiency
7. UGT1A1*28 7/7
8. the MSI status is MSS or p-MMR
9. allergic to any component of the therapy