Back to resultsA Study of Chemoradiation in Combination With Tislelizumab as First Line Treatment in Participants With Advanced Esophageal Squamous Cell Carcinoma
Primary Purpose
Esophageal Squamous Cell Carcinoma
Status
Recruiting
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
Intensity-modulated radiotherapy (IMRT)
Tislelizumab
Cisplatin
Nab paclitaxel
Sponsored by
About this trial
This is an interventional treatment trial for Esophageal Squamous Cell Carcinoma focused on measuring Chemoradiation, Immunotherapy, Advanced esophageal cancer, Low PD-L1 expression, Progression-free survival
Eligibility Criteria
Inclusion Criteria: Subjects must have histologically confirmed squamous cell carcinoma of esophagus (per AJCC 8th edition). Subjects must have unresectable advanced, recurrent or metastatic ESCC. Subjects must not be amenable to curative approaches such as definitive chemoradiation and/or surgery. PD-L1 expression (CPS) is less than 10. No prior systemic anticancer therapy given as primary therapy for advanced or metastatic disease. ECOG Performance Status of 0 or 1. Subjects must have at least one measurable lesion by CT or MRI per RECIST 1.1 criteria; radiographic tumor assessment must be performed within 28 days prior to randomization. Subjects must have adequate organ and bone marrow function. Exclusion Criteria: Presence of tumor cells in the brain or spinal cord which are symptomatic or require treatment. Active known or suspected autoimmune disease. Any serious or uncontrolled medical disorder or active infection. Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS). Any positive test result for hepatitis B or C indicating acute or chronic infection and/or detectable virus. Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
Sites / Locations
- Renmin hosptial of Wuhan UniversityRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Chemoradiation + Tislelizumab
Chemotherapy + Tislelizumab
Arm Description
Intensity-modulated radiotherapy (IMRT): Esophageal primary tumor: 39.6Gy/2.2Gy Bone metastasis: 30Gy/3Gy Lung, liver, brain metastases, metastatic lymph nodes: 45Gy/3Gy During concurrent radiation therapy: Drug: Tislelizumab 200 mg IV Q3W Drug: Nab Paclitaxel 75 mg/m² IV QW Drug: Cisplatin 25 mg/m² IV QW During consolidation therapy: Drug: Tislelizumab 200 mg IV Q3W Drug: Nab Paclitaxel 220 mg/m² IV Q3W Drug: Cisplatin 75 mg/m² IV Q3W
Drug: Tislelizumab 200 mg IV Q3W Drug: Nab Paclitaxel 220 mg/m² IV Q3W Drug: Cisplatin 75 mg/m² IV Q3W
Outcomes
Primary Outcome Measures
Progression-Free Survival (PFS)
PFS is defined as the time from the date of randomization to the date of first documentation of disease progression assessed by the investigator per RECIST v1.1 or death, whichever occurs first
Secondary Outcome Measures
Overall Survival (OS)
Overall Survival (OS) is defined as the time between the date of randomization and the date of death. For participants without documentation of death, OS will be censored on the last date the subject was known to be alive.
Objective Response Rate (ORR)
Objective response rate (ORR) is defined as the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR). Best overall response (BOR) is defined as the best response designation as determined by BICR, recorded between the date of randomization and the date of objectively documented progression (per RECIST 1.1) or the date of subsequent anti-cancer therapy (including tumor-directed radiotherapy and tumor-directed surgery), whichever occurs first. Partial response is defined as at least a 30% decrease in the sum of diameters of target lesions. Complete response is defined as the disappearance of all target lesions and the reduction of any pathological lymph nodes to <10 mm.
Duration of Response (DOR)
DOR is defined as the time from the first determination of an objective response until the first documentation of progression assessed by the investigator per RECIST v1.1 or death, whichever comes first
Number of participants experiencing Adverse Events (AEs)
AEs are documented according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v4
Full Information
NCT ID
NCT05919030
First Posted
June 16, 2023
Last Updated
July 19, 2023
Sponsor
Renmin Hospital of Wuhan University
1. Study Identification
Unique Protocol Identification Number
NCT05919030
Brief Title
A Study of Chemoradiation in Combination With Tislelizumab as First Line Treatment in Participants With Advanced Esophageal Squamous Cell Carcinoma
Official Title
Chemoradiation Versus Chemotherapy in Combination With Tislelizumab as First Line Treatment for Advanced Esophageal Squamous Cell Carcinoma With Low PD-L1 Expression (RENMIN-236): Multicentre, Randomised, Phase 3 Trial
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 1, 2023 (Actual)
Primary Completion Date
July 1, 2026 (Anticipated)
Study Completion Date
July 1, 2027 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Renmin Hospital of Wuhan University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This study is a multicentre, randomised, parallel-controlled, open-label, 3 phase clinical trial. The subjects were untreated, unresectable locally advanced, recurrent or metastatic esophageal squamous cell carcinoma with low PD-L1 expression. Patients were randomly assigned to receive chemoradiation or chemotherapy in combination with Tislelizumab at a ratio of 1: 1. The primary endpoint was progression-free survival (PFS) in the intention-to-treat population. We hypothesized that in advanced esophageal squamous cell carcinoma patients with low PD-L1 expression, chemoradiation versus chemotherapy in combination with Tislelizumab will significantly improve PFS.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Esophageal Squamous Cell Carcinoma
Keywords
Chemoradiation, Immunotherapy, Advanced esophageal cancer, Low PD-L1 expression, Progression-free survival
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
155 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Chemoradiation + Tislelizumab
Arm Type
Experimental
Arm Description
Intensity-modulated radiotherapy (IMRT):
Esophageal primary tumor: 39.6Gy/2.2Gy Bone metastasis: 30Gy/3Gy Lung, liver, brain metastases, metastatic lymph nodes: 45Gy/3Gy
During concurrent radiation therapy:
Drug: Tislelizumab 200 mg IV Q3W Drug: Nab Paclitaxel 75 mg/m² IV QW Drug: Cisplatin 25 mg/m² IV QW
During consolidation therapy:
Drug: Tislelizumab 200 mg IV Q3W Drug: Nab Paclitaxel 220 mg/m² IV Q3W Drug: Cisplatin 75 mg/m² IV Q3W
Arm Title
Chemotherapy + Tislelizumab
Arm Type
Active Comparator
Arm Description
Drug: Tislelizumab 200 mg IV Q3W Drug: Nab Paclitaxel 220 mg/m² IV Q3W Drug: Cisplatin 75 mg/m² IV Q3W
Intervention Type
Radiation
Intervention Name(s)
Intensity-modulated radiotherapy (IMRT)
Intervention Description
Esophageal primary tumor: 39.6Gy/2.2Gy Bone metastasis: 30Gy/3Gy Lung, liver, brain metastases, metastatic lymph nodes: 45Gy/3Gy
Intervention Type
Drug
Intervention Name(s)
Tislelizumab
Intervention Description
200 mg IV Q3W
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Intervention Description
During concurrent radiation therapy: 25 mg/m² IV QW During consolidation therapy: 75 mg/m² IV Q3W
Intervention Type
Drug
Intervention Name(s)
Nab paclitaxel
Intervention Description
During concurrent radiation therapy: 75 mg/m² IV QW During consolidation therapy: 220 mg/m² IV Q3W
Primary Outcome Measure Information:
Title
Progression-Free Survival (PFS)
Description
PFS is defined as the time from the date of randomization to the date of first documentation of disease progression assessed by the investigator per RECIST v1.1 or death, whichever occurs first
Time Frame
Approximately 40 months from date of the first participant randomization
Secondary Outcome Measure Information:
Title
Overall Survival (OS)
Description
Overall Survival (OS) is defined as the time between the date of randomization and the date of death. For participants without documentation of death, OS will be censored on the last date the subject was known to be alive.
Time Frame
Approximately 40 months from date of the first participant randomization
Title
Objective Response Rate (ORR)
Description
Objective response rate (ORR) is defined as the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR). Best overall response (BOR) is defined as the best response designation as determined by BICR, recorded between the date of randomization and the date of objectively documented progression (per RECIST 1.1) or the date of subsequent anti-cancer therapy (including tumor-directed radiotherapy and tumor-directed surgery), whichever occurs first. Partial response is defined as at least a 30% decrease in the sum of diameters of target lesions. Complete response is defined as the disappearance of all target lesions and the reduction of any pathological lymph nodes to <10 mm.
Time Frame
Approximately 40 months from date of the first participant randomization
Title
Duration of Response (DOR)
Description
DOR is defined as the time from the first determination of an objective response until the first documentation of progression assessed by the investigator per RECIST v1.1 or death, whichever comes first
Time Frame
Approximately 40 months from date of the first participant randomization
Title
Number of participants experiencing Adverse Events (AEs)
Description
AEs are documented according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v4
Time Frame
Approximately 40 months from date of the first participant randomization
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Subjects must have histologically confirmed squamous cell carcinoma of esophagus (per AJCC 8th edition).
Subjects must have unresectable advanced, recurrent or metastatic ESCC.
Subjects must not be amenable to curative approaches such as definitive chemoradiation and/or surgery.
PD-L1 expression (CPS) is less than 10.
No prior systemic anticancer therapy given as primary therapy for advanced or metastatic disease.
ECOG Performance Status of 0 or 1.
Subjects must have at least one measurable lesion by CT or MRI per RECIST 1.1 criteria; radiographic tumor assessment must be performed within 28 days prior to randomization.
Subjects must have adequate organ and bone marrow function.
Exclusion Criteria:
Presence of tumor cells in the brain or spinal cord which are symptomatic or require treatment.
Active known or suspected autoimmune disease.
Any serious or uncontrolled medical disorder or active infection.
Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
Any positive test result for hepatitis B or C indicating acute or chronic infection and/or detectable virus.
Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yongshun Chen, MD
Phone
+86 15327122084
Email
yongshun2007@163.com
Facility Information:
Facility Name
Renmin hosptial of Wuhan University
City
Wuhan
State/Province
Hubei
ZIP/Postal Code
430060
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Liwei Chen
Phone
86+15671578311
Email
wdrmiit@163.com
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Study of Chemoradiation in Combination With Tislelizumab as First Line Treatment in Participants With Advanced Esophageal Squamous Cell Carcinoma
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