The Combination of Immunotherapy and Neoadjuvant Chemoradiotherapy in MSS Locally Advanced Rectal Cancer

Locally Advanced Rectal Cancer Clinical Trial

Official title:

A Phase II Trial of Immunotherapy Combined With Neoadjuvant Chemoradiotherapy in Microsatellite Stable Locally Advanced Rectal Cancer

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04411537
• Other study ID #: FDRT-2019-97-1731
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: July 1, 2020
• Est. completion date: December 31, 2022

Study information

• Verified date: May 2020
• Source: Fudan University
• Contact: zhen zhang, M.D, PH.D
• Phone: 18801735029
• Email: zhen_zhang[@]fudan.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study evaluates the addition of immunotherapy of PD-1 antibody in neoadjuvant chemoradiotherapy in microsatellite stable (MSS) locally advanced rectal cancer (LARC). A total of 50 MSS 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 50
• Est. completion date: December 31, 2022
• Est. primary completion date: April 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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 MSS or p-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 MSI-H or d-MMR

9. allergic to any component of the therapy

Related Conditions & MeSH terms

• Locally Advanced Rectal Cancer
• Rectal Neoplasms

Intervention

Drug:
• PD-1 antibody
Before neo-CRT: 2 cycles of PD-1 antibody, 240mg d1 q2w. After neo-CRT: 3 cycles of PD-1 antibody, 240mg d1 q2w.
• Capecitabine
During neo-CRT: 625mg/m2 bid Monday-Friday per week
• 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

Locations

Country	Name	City	State
China	Zhen Zhang	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Fudan University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pathologic Complete Response Rate	Pathologic Complete Response Rate	The pathologic complete response rate was evaluated after surgery, which was scheduled 7-8 weeks after the end of chemoradiotherapy
Secondary	Disease free survival	3 year disease free survival rate	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.
Secondary	Local recurrence free survival	3 year local recurrence free survival rate	From date of randomization until the date of first documented pelvic failure, assessed up to 36 months.
Secondary	Overall survival	3 year overall survival rate	From date of randomization until the date of death from any cause, assessed up to 36 months.
Secondary	Adverse effects	Chemoradiation-related or immunotherapy-related adverse events	From date of randomization until the date of death from any cause, assessed up to 5 years
Secondary	Surgical complications	Surgical complications, such as intraoperative hemorrhage, anastomotic leakage, intestinal obstruction, etc.	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.
Secondary	Performance Status (Zubrod-ECOG-WHO method), range 0-5. The higher scores mean a worse quality of life.	Quality of life will be evaluated	From date of randomization until the date of death from any cause, assessed up to 10 years
Secondary	Karnofsky Performance Status, range 0-100. The higher scores mean a better quality of life.	Quality of life will be evaluated	From date of randomization until the date of death from any cause, assessed up to 10 years
Secondary	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.	Quality of life will be evaluated	From date of randomization until the date of death from any cause, assessed up to 10 years