The Combination of Immunotherapy and Neoadjuvant Chemoradiotherapy in MSI-H Locally Advanced Rectal Cancer
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Treatment Arm 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
Before neo-CRT: 2 cycles of PD-1 antibody After neo-CRT: 3 cycles of PD-1 antibody
Drug: Capecitabine
During neo-CRT: 625mg/m2 bid Monday-Friday per week
Other Names:
Drug: Irinotecan
During neo-CRT: 80mg/m2 qw (UGT1A1*28 6/6) or 65mg/m2 qw (UGT1A1*28 6/7)
Radiation: Neoadjuvant Radiotherapy
IMRT DT: 50Gy/25Fx
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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
- 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
- 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.
- 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
Eligibility Criteria
Criteria
Inclusion Criteria:
-
pathological confirmed adenocarcinoma
-
clinical stage T3-4 and/or N+
-
the distance from anal verge less than 12 cm
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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
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without previous anti-cancer therapy or immunotherapy
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with good compliance
-
signed the inform consent
Exclusion Criteria:
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pregnancy or breast-feeding women
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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
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baseline blood and biochemical indicators do not meet the following criteria: neutrophils≥1.5×109/L, Hb≥90g/L, PLT≥100×109/L, ALT/AST ≤2.5 ULN, Cr≤ 1 ULN
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DPD deficiency
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UGT1A1*28 7/7
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the MSI status is MSS or p-MMR
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allergic to any component of the therapy
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Zhen Zhang | Shanghai | Shanghai | China | 200032 |
Sponsors and Collaborators
- Fudan University
Investigators
- Principal Investigator: Zhen Zhang, M.D, PH.D, Fudan University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- FDRT-2019-104-1734