Locally Advanced Rectal Cancer
Conditions
Brief summary
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.
Interventions
DRUGPD-1 antibody
Before neo-CRT: 2 cycles of PD-1 antibody After neo-CRT: 3 cycles of PD-1 antibody
DRUGCapecitabine
During neo-CRT: 625mg/m2 bid Monday-Friday per week
DRUGIrinotecan
During neo-CRT: 80mg/m2 qw (UGT1A1\*28 6/6) or 65mg/m2 qw (UGT1A1\*28 6/7)
RADIATIONNeoadjuvant Radiotherapy
IMRT DT: 50Gy/25Fx
Sponsors
Fudan University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
15 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pathologic Complete Response Rate | The pathologic complete response rate was evaluated after surgery, which was scheduled 7-8 weeks after the end of chemoradiotherapy. | Pathologic Complete Response Rate |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Local recurrence free survival | From date of randomization until the date of first documented pelvic failure, assessed up to 36 months. | 3 year local recurrence free survival rate |
| Overall survival | From date of randomization until the date of death from any cause, assessed up to 36 months. | 3 year overall survival rate |
| Adverse effects | From date of randomization until the date of death from any cause, assessed up to 5 years | Chemoradiation-related or immunotherapy-related adverse events |
| 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 36 months. | 3 year disease free survival rate |
| Performance Status (Zubrod-ECOG-WHO method), range 0-5. The higher scores mean a worse quality of life. | From date of randomization until the date of death from any cause, assessed up to 10 years | Quality of life will be evaluated |
| Karnofsky Performance Status, range 0-100. The higher scores mean a better quality of life. | From date of randomization until the date of death from any cause, assessed up to 10 years | Quality of life will be evaluated |
| 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. | From date of randomization until the date of death from any cause, assessed up to 10 years | Quality of life will be evaluated |
| Surgical complications | 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. | Surgical complications, such as intraoperative hemorrhage, anastomotic leakage, intestinal obstruction, etc. |
Countries
China
Contacts
Primary ContactZhen Zhang, M.D, PH.D
Outcome results
None listed