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

Primary Purpose

Locally Advanced Rectal Cancer

Status

Unknown status

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

PD-1 antibody

Capecitabine

Irinotecan

Neoadjuvant Radiotherapy

About this trial

This is an interventional treatment trial for Locally Advanced Rectal Cancer

Eligibility Criteria

15 Years - 70 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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
KPS >=70
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

Sites / Locations

Zhen Zhang

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment Arm

Arm Description

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.

Outcomes

Primary Outcome Measures

Pathologic Complete Response Rate

Secondary Outcome Measures

Disease free survival

3 year disease free survival rate

Local recurrence free survival

3 year local recurrence free survival rate

Overall survival

3 year overall survival rate

Adverse effects

Chemoradiation-related or immunotherapy-related adverse events

Surgical complications

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.

Quality of life will be evaluated

Karnofsky Performance Status, range 0-100. The higher scores mean a better quality of life.

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.

Quality of life will be evaluated

Full Information

NCT ID

NCT04411524

First Posted

May 10, 2020

Last Updated

June 1, 2020

Sponsor

Fudan University

1. Study Identification

Unique Protocol Identification Number

NCT04411524

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2020

Overall Recruitment Status

Unknown status

Study Start Date

July 1, 2020 (Anticipated)

Primary Completion Date

April 30, 2022 (Anticipated)

Study Completion Date

December 31, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Fudan University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Locally Advanced Rectal Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Treatment Arm

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

PD-1 antibody

Intervention Description

Before neo-CRT: 2 cycles of PD-1 antibody After neo-CRT: 3 cycles of PD-1 antibody

Intervention Type

Drug

Intervention Name(s)

Capecitabine

Other Intervention Name(s)

Xeloda

Intervention Description

During neo-CRT: 625mg/m2 bid Monday-Friday per week

Intervention Type

Drug

Intervention Name(s)

Irinotecan

Intervention Description

During neo-CRT: 80mg/m2 qw (UGT1A1*28 6/6) or 65mg/m2 qw (UGT1A1*28 6/7)

Intervention Type

Radiation

Intervention Name(s)

Neoadjuvant Radiotherapy

Intervention Description

IMRT DT: 50Gy/25Fx

Primary Outcome Measure Information:

Title

Pathologic Complete Response Rate

Description

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.

Secondary Outcome Measure Information:

Title

Disease free survival

Description

3 year disease free survival rate

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.

Title

Local recurrence free survival

Description

3 year local recurrence free survival rate

Time Frame

From date of randomization until the date of first documented pelvic failure, assessed up to 36 months.

Title

Overall survival

Description

3 year overall survival rate

Time Frame

From date of randomization until the date of death from any cause, assessed up to 36 months.

Title

Adverse effects

Description

Chemoradiation-related or immunotherapy-related adverse events

Time Frame

From date of randomization until the date of death from any cause, assessed up to 5 years

Title

Surgical complications

Description

Surgical complications, such as intraoperative hemorrhage, anastomotic leakage, intestinal obstruction, etc.

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.

Title

Performance Status (Zubrod-ECOG-WHO method), range 0-5. The higher scores mean a worse quality of life.

Description

Quality of life will be evaluated

Time Frame

From date of randomization until the date of death from any cause, assessed up to 10 years

Title

Karnofsky Performance Status, range 0-100. The higher scores mean a better quality of life.

Description

Quality of life will be evaluated

Time Frame

From date of randomization until the date of death from any cause, assessed up to 10 years

Title

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.

Description

Quality of life will be evaluated

Time Frame

From date of randomization until the date of death from any cause, assessed up to 10 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

15 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

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 KPS >=70 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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Zhen Zhang, M.D, PH.D

Phone

18801735029

Ext

18801735029

zhen_zhang@fudan.edu.cn

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Zhen Zhang, M.D, PH.D

Organizational Affiliation

Fudan University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Zhen Zhang

City

Shanghai

State/Province

Shanghai

ZIP/Postal Code

200032

Country

China

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Zhen Zhang, M.D, PH.D

Phone

18801735029

Ext

18801735029

zhen_zhang@fudan.edu.cn

12. IPD Sharing Statement

Learn more about this trial

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

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