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

June 1, 2020 updated by: Zhen Zhang, Fudan University

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

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 Overview

Status

Unknown

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

50

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Shanghai
      • Shanghai, Shanghai, China, 200032
        • Zhen Zhang

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

15 years to 70 years (ADULT, OLDER_ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / 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: Capecitabine
During neo-CRT: 625mg/m2 bid Monday-Friday per week
Other Names:
  • Xeloda
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
Drug: PD-1 antibody
Before neo-CRT: 2 cycles of PD-1 antibody After neo-CRT: 3 cycles of PD-1 antibody

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
The pathologic complete response rate was evaluated after surgery, which was scheduled 7-8 weeks after the end of chemoradiotherapy.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
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.
Local recurrence free survival
Time Frame: From date of randomization until the date of first documented pelvic failure, assessed up to 36 months.
3 year local recurrence free survival rate
From date of randomization until the date of first documented pelvic failure, assessed up to 36 months.
Overall survival
Time Frame: From date of randomization until the date of death from any cause, assessed up to 36 months.
3 year overall survival rate
From date of randomization until the date of death from any cause, assessed up to 36 months.
Adverse effects
Time Frame: From date of randomization until the date of death from any cause, assessed up to 5 years
Chemoradiation-related or immunotherapy-related adverse events
From date of randomization until the date of death from any cause, assessed up to 5 years
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.
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.
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
Quality of life will be evaluated
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.
Time Frame: From date of randomization until the date of death from any cause, assessed up to 10 years
Quality of life will be evaluated
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.
Time Frame: From date of randomization until the date of death from any cause, assessed up to 10 years
Quality of life will be evaluated
From date of randomization until the date of death from any cause, assessed up to 10 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fudan University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ANTICIPATED)

July 1, 2020

Primary Completion (ANTICIPATED)

April 30, 2022

Study Completion (ANTICIPATED)

December 31, 2022

Study Registration Dates

First Submitted

May 10, 2020

First Submitted That Met QC Criteria

June 1, 2020

First Posted (ACTUAL)

June 2, 2020

Study Record Updates

Last Update Posted (ACTUAL)

June 2, 2020

Last Update Submitted That Met QC Criteria

June 1, 2020

Last Verified

May 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FDRT-2019-104-1734

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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