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Total Neoadjuvant Therapy Combined With Tislelizumab for Local Advanced of Middle and Low Rectal Cancer

Primary Purpose

Locally Advanced Rectal Cancer

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Long-course chemoradiation, with Tislelizumab (PD-1 inhibitor)
Long-course chemoradiation, without Tislelizumab (PD-1 inhibitor)
Sponsored by
Beijing Friendship Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Locally Advanced Rectal Cancer focused on measuring neoadjuvant, Tislelizumab, PD-1, chemoradiation, LARC, randomized, controlled

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Patients have been fully aware of the content of this study and signed the informed consent voluntarily; Patients with rectal cancers must satisfied all the following conditions:Stage II/III LARC (cT3-4aN0M0 and cT1-4aN1-2M0);Tumor distal location ≤ 10 cm from anal verge (MRI diagnosed); Patients regardless of gender with aged ≥18 years and ECOG score of 0 or 1; Physical and viscera function of patients can withstand major abdominal surgery; Patients are willing and able to follow the study protocol during the study; Patients give consent to the use of blood and pathological specimens for study; Within 28 days prior to enrolment, we must confirm a negative serological pregnancy test for child-bearing age women and they agree to use effective contraception for the duration of drug use and for 60 days after the last dose. Exclusion Criteria: Patients have a present or previous active malignancy except the diagnosis of rectal cancer this time; Patients underwent major surgery within 4 weeks prior to study treatment; Patients have any condition affects the absorption of capecitabine through gastrointestinal tract; Patients have severe uncontrolled recurrent infections, or other severe uncontrolled concomitant diseases; Patients who are allergic to any of the ingredients under study; Patients with severe concomitant diseases with estimated survival ≤ 5 years; Patients with present or previous moderate or severe liver and kidney damage presently or previously; Patients have received other study medications or any immunotherapy currently or in the past; Patients preparing for or previously received organ or bone marrow transplant; Patients who received immunosuppressive or systemic hormone therapy for immunosuppressive purposes within 1 month prior to the initiation of study therapy; Patients with congenital or acquired immune deficiency (such as HIV infection); If patients with a history of uncontrolled epilepsy, central nervous system disease or mental disorder, the investigator will determine whether the clinical severity prevents the signing of informed consent or affects the patient's oral medication compliance; Patients with other factors that may affect the study results or cause the study to be terminated midway, such as alcoholism, drug abuse, other serious diseases (including mental illness) requiring combined treatment and severe laboratory examination abnormalities. Pregnant or lactating women

Sites / Locations

  • Beijing Friendship Hospital, Capital Medical UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

CRT+concurrent PD-1 inhibition

CRT without PD-1 inhibition

Arm Description

Long-course chemoradiation plus PD-1 inhibition (Tislelizumab 200mg, 3 times, 3-week interval) starting on Day 8 of radiation therapy. TME surgery is scheduled in 10~13 weeks after completion of radiation.

Long-course chemoradiation plus PD-1 inhibition with no PD-1 inhibition. TME surgery is scheduled in 10~13 weeks after completion of radiation.

Outcomes

Primary Outcome Measures

pCR rate
pathological complete response rate
cCR rate
clinical complete response rate

Secondary Outcome Measures

NAR score
Neoadjuvant rectal(NAR)score:It is based on the scoring criteria of preoperative treatment downstaging. The range is 0-201.46, with higher scores indicating worse prognosis.
OPR
organ preservation rate
ORR
objective response rate
immune-related adverse event rate
adverse event rate that is deemed to be associated with PD-1 inhibition

Full Information

First Posted
March 30, 2023
Last Updated
April 25, 2023
Sponsor
Beijing Friendship Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT05845268
Brief Title
Total Neoadjuvant Therapy Combined With Tislelizumab for Local Advanced of Middle and Low Rectal Cancer
Official Title
Total Neoadjuvant Therapy Combined With Tislelizumab for Local Advanced Phase II Randomized Controlled Clinical Study of Middle and Low Rectal Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Recruiting
Study Start Date
October 1, 2022 (Actual)
Primary Completion Date
November 1, 2024 (Anticipated)
Study Completion Date
December 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Beijing Friendship Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This study is a prospective, randomized, open, controlled, multi-center phase II clinical trial, which included patients with locally advanced low rectal cancer as the research object, and evaluated the application of long-term concurrent chemoradiotherapy combined with tislelizumab versus long-term synchronous Efficacy and safety of chemotherapy and radiotherapy as neoadjuvant therapy for patients with locally advanced rectal cancer. The main endpoints of the study were clinical complete response (cCR) (including imaging and endoscopic complete response) and pathological complete response (pathological complete response, pCR). Secondary study endpoints are primary pathological response rate (MPR), objective response rate (ORR), disease-free survival (DFS), overall survival (OS), organ preservation rate (OPR), rectal cancer neoadjuvant therapy score (NAR ), quality of life score (QoL), safety and tolerability. They will be randomly divided into an experimental group (tislelizumab combined with long-term concurrent chemoradiotherapy) and a control group (long-term concurrent chemoradiotherapy) at a ratio of 2:1. Random stratification factors: 1. TNM stage (II/III); 2. Distance from the tumor to the anal verge (≥5cm, <5cm).
Detailed Description
This study plans to recruit 102 patients, aged 18-75 years old, male or female; rectal adenocarcinoma confirmed by histopathology; clinical stage II-III assessed by MRI (according to AJCC 8th edition); Margin ≤ 10 cm; surgical resection is possible.All patients should have no history of immune diseases, nor history of immunotherapy or radiotherapy. Eligible participants will be randomly assigned to Experiment Arm (50.4Gy radiation, capecitabine, and anti-PD1 starting at Day 8 of radiation) and Control Arm (50.4Gy radiation, capecitabine) in a 2:1ratio.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Locally Advanced Rectal Cancer
Keywords
neoadjuvant, Tislelizumab, PD-1, chemoradiation, LARC, randomized, controlled

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Masking Description
Masking is not practically possible
Allocation
Randomized
Enrollment
102 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
CRT+concurrent PD-1 inhibition
Arm Type
Experimental
Arm Description
Long-course chemoradiation plus PD-1 inhibition (Tislelizumab 200mg, 3 times, 3-week interval) starting on Day 8 of radiation therapy. TME surgery is scheduled in 10~13 weeks after completion of radiation.
Arm Title
CRT without PD-1 inhibition
Arm Type
Active Comparator
Arm Description
Long-course chemoradiation plus PD-1 inhibition with no PD-1 inhibition. TME surgery is scheduled in 10~13 weeks after completion of radiation.
Intervention Type
Combination Product
Intervention Name(s)
Long-course chemoradiation, with Tislelizumab (PD-1 inhibitor)
Intervention Description
Tislelizumab was added to long-course chemoradiotherapy (CRT) in LARC patients, CRT + concurrent tislelizumab was used in the Experimental arm, and CRT was used in the Active Comparator arm.
Intervention Type
Combination Product
Intervention Name(s)
Long-course chemoradiation, without Tislelizumab (PD-1 inhibitor)
Intervention Description
Tislelizumab was added to long-course chemoradiotherapy (CRT) in LARC patients, CRT + concurrent tislelizumab was used in the Experimental arm, and CRT was used in the Active Comparator arm.
Primary Outcome Measure Information:
Title
pCR rate
Description
pathological complete response rate
Time Frame
within 10 days after surgery
Title
cCR rate
Description
clinical complete response rate
Time Frame
12-13 weeks after radiotherapy ends
Secondary Outcome Measure Information:
Title
NAR score
Description
Neoadjuvant rectal(NAR)score:It is based on the scoring criteria of preoperative treatment downstaging. The range is 0-201.46, with higher scores indicating worse prognosis.
Time Frame
within 10 days after surgery
Title
OPR
Description
organ preservation rate
Time Frame
immediately after surgery
Title
ORR
Description
objective response rate
Time Frame
within 10 days after surgery
Title
immune-related adverse event rate
Description
adverse event rate that is deemed to be associated with PD-1 inhibition
Time Frame
up to 30th day after surgery

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients have been fully aware of the content of this study and signed the informed consent voluntarily; Patients with rectal cancers must satisfied all the following conditions:Stage II/III LARC (cT3-4aN0M0 and cT1-4aN1-2M0);Tumor distal location ≤ 10 cm from anal verge (MRI diagnosed); Patients regardless of gender with aged ≥18 years and ECOG score of 0 or 1; Physical and viscera function of patients can withstand major abdominal surgery; Patients are willing and able to follow the study protocol during the study; Patients give consent to the use of blood and pathological specimens for study; Within 28 days prior to enrolment, we must confirm a negative serological pregnancy test for child-bearing age women and they agree to use effective contraception for the duration of drug use and for 60 days after the last dose. Exclusion Criteria: Patients have a present or previous active malignancy except the diagnosis of rectal cancer this time; Patients underwent major surgery within 4 weeks prior to study treatment; Patients have any condition affects the absorption of capecitabine through gastrointestinal tract; Patients have severe uncontrolled recurrent infections, or other severe uncontrolled concomitant diseases; Patients who are allergic to any of the ingredients under study; Patients with severe concomitant diseases with estimated survival ≤ 5 years; Patients with present or previous moderate or severe liver and kidney damage presently or previously; Patients have received other study medications or any immunotherapy currently or in the past; Patients preparing for or previously received organ or bone marrow transplant; Patients who received immunosuppressive or systemic hormone therapy for immunosuppressive purposes within 1 month prior to the initiation of study therapy; Patients with congenital or acquired immune deficiency (such as HIV infection); If patients with a history of uncontrolled epilepsy, central nervous system disease or mental disorder, the investigator will determine whether the clinical severity prevents the signing of informed consent or affects the patient's oral medication compliance; Patients with other factors that may affect the study results or cause the study to be terminated midway, such as alcoholism, drug abuse, other serious diseases (including mental illness) requiring combined treatment and severe laboratory examination abnormalities. Pregnant or lactating women
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Zhang Zhongtao, MD
Phone
+8613801060364
Email
zhangzht@ccmu.edu.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Zhang Zhongtao
Organizational Affiliation
Beijing Friendship Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Beijing Friendship Hospital, Capital Medical University
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100050
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yao Hongwei, M.D
Phone
86 13611015609
Email
yaohongwei@ccmu.edu.cn

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
Export of individual patient data is a sensitive issue according to current Chinese laws

Learn more about this trial

Total Neoadjuvant Therapy Combined With Tislelizumab for Local Advanced of Middle and Low Rectal Cancer

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