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

Phase 2

• Conditions: Locally Advanced Rectal Cancer
• Interventions: Drug: PD-1 antibody; Drug: Capecitabine; Drug: Irinotecan; Radiation: Neoadjuvant Radiotherapy

• Registration Number: NCT04411524
• Lead Sponsor: Fudan University

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2020-05
• Study First Submitted: 2020-05-10
• Study First Submitted QC: 2020-06-01
• Last Update Submitted: 2020-06-01
• Study First Posted: 2020-06-02
• Last Update Posted: 2020-06-02
• Study Start: 2020-07-01
• Primary Completion: 2022-04-30
• Study Completion: 2022-12-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 50

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment Arm	PD-1 antibody	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.
Treatment Arm	Neoadjuvant Radiotherapy	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.
Treatment Arm	Capecitabine	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.
Treatment Arm	Irinotecan	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.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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
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

Trial Locations

Locations (1)

Zhen Zhang; 🇨🇳 Shanghai, Shanghai, China