A Phase II Trial of Immunotherapy Combined With Neoadjuvant Chemoradiotherapy in Microsatellite Instability-High Locally Advanced Rectal Cancer
Trial Snapshot
- Phase
- Phase 2
- Sponsor
- Fudan University
- Enrollment
- 50
- Locations
- 1
- Primary Endpoint
- Pathologic Complete Response Rate
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 15 Years to 70 Years (Child, Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
- •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
Arms & Interventions
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.
Intervention: PD-1 antibody (Drug)
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.
Intervention: Capecitabine (Drug)
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.
Intervention: Irinotecan (Drug)
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.
Intervention: Neoadjuvant Radiotherapy (Radiation)
Outcomes
Primary Outcomes
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.
Pathologic Complete Response Rate
Secondary Outcomes
- Overall survival(From date of randomization until the date of death from any cause, assessed up to 36 months.)
- Adverse effects(From date of randomization until the date of death from any cause, assessed up to 5 years)
- 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.)
- 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)
- 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 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)
- 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.)
- Local recurrence free survival(From date of randomization until the date of first documented pelvic failure, assessed up to 36 months.)
Investigators
Zhen Zhang
Professor
Fudan University