Description:
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.
Title
- Brief Title: The Combination of Immunotherapy and Neoadjuvant Chemoradiotherapy in MSI-H Locally Advanced Rectal Cancer
- Official Title: A Phase II Trial of Immunotherapy Combined With Neoadjuvant Chemoradiotherapy in Microsatellite Instability-High Locally Advanced Rectal Cancer
Clinical Trial IDs
- ORG STUDY ID:
FDRT-2019-104-1734
- NCT ID:
NCT04411524
Conditions
- Locally Advanced Rectal Cancer
Interventions
| Drug | Synonyms | Arms |
|---|
| PD-1 antibody | | Treatment Arm |
| Capecitabine | Xeloda | Treatment Arm |
| Irinotecan | | Treatment Arm |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Treatment Arm | Experimental | 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. | - PD-1 antibody
- Capecitabine
- Irinotecan
|
Eligibility Criteria
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
| Maximum Eligible Age: | 70 Years |
| Minimum Eligible Age: | 15 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Pathologic Complete Response Rate |
| Time Frame: | The pathologic complete response rate was evaluated after surgery, which was scheduled 7-8 weeks after the end of chemoradiotherapy. |
| Safety Issue: | |
| Description: | Pathologic Complete Response Rate |
Secondary Outcome Measures
| Measure: | Disease free survival |
| Time Frame: | 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. |
| Safety Issue: | |
| Description: | 3 year disease free survival rate |
| Measure: | Local recurrence free survival |
| Time Frame: | From date of randomization until the date of first documented pelvic failure, assessed up to 36 months. |
| Safety Issue: | |
| Description: | 3 year local recurrence free survival rate |
| Measure: | Overall survival |
| Time Frame: | From date of randomization until the date of death from any cause, assessed up to 36 months. |
| Safety Issue: | |
| Description: | 3 year overall survival rate |
| Measure: | Adverse effects |
| Time Frame: | From date of randomization until the date of death from any cause, assessed up to 5 years |
| Safety Issue: | |
| Description: | Chemoradiation-related or immunotherapy-related adverse events |
| Measure: | Surgical complications |
| Time Frame: | 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. |
| Safety Issue: | |
| Description: | Surgical complications, such as intraoperative hemorrhage, anastomotic leakage, intestinal obstruction, etc. |
| Measure: | Performance Status (Zubrod-ECOG-WHO method), range 0-5. The higher scores mean a worse quality of life. |
| Time Frame: | From date of randomization until the date of death from any cause, assessed up to 10 years |
| Safety Issue: | |
| Description: | Quality of life will be evaluated |
| Measure: | Karnofsky Performance Status, range 0-100. The higher scores mean a better quality of life. |
| Time Frame: | From date of randomization until the date of death from any cause, assessed up to 10 years |
| Safety Issue: | |
| Description: | Quality of life will be evaluated |
| Measure: | 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. |
| Time Frame: | From date of randomization until the date of death from any cause, assessed up to 10 years |
| Safety Issue: | |
| Description: | Quality of life will be evaluated |
Details
| Phase: | Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Not yet recruiting |
| Lead Sponsor: | Fudan University |
Last Updated
June 2, 2020
