A Study of Chemoradiation in Combination With Tislelizumab as First Line Treatment in Participants With Advanced Esophageal Squamous Cell Carcinoma

Esophageal Squamous Cell Carcinoma Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05919030
• Other study ID #: WDRY2023-K088
• Status: Recruiting
• Phase: Phase 3
• Start date: July 1, 2023
• Est. completion date: July 1, 2027

Study information

• Verified date: July 2023
• Source: Renmin Hospital of Wuhan University
• Contact: Yongshun Chen, MD
• Phone: +86 15327122084
• Email: yongshun2007[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 155
• Est. completion date: July 1, 2027
• Est. primary completion date: July 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Subjects must have histologically confirmed squamous cell carcinoma of esophagus (per AJCC 8th edition).

2. Subjects must have unresectable advanced, recurrent or metastatic ESCC.

3. Subjects must not be amenable to curative approaches such as definitive chemoradiation and/or surgery.

4. PD-L1 expression (CPS) is less than 10.

5. No prior systemic anticancer therapy given as primary therapy for advanced or metastatic disease.

6. ECOG Performance Status of 0 or 1.

7. 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.

8. Subjects must have adequate organ and bone marrow function.

Exclusion Criteria:

1. Presence of tumor cells in the brain or spinal cord which are symptomatic or require treatment.

2. Active known or suspected autoimmune disease.

3. Any serious or uncontrolled medical disorder or active infection.

4. Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).

5. Any positive test result for hepatitis B or C indicating acute or chronic infection and/or detectable virus.

6. 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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Esophageal Squamous Cell Carcinoma

Intervention

Radiation:
• Intensity-modulated radiotherapy (IMRT)
Esophageal primary tumor: 39.6Gy/2.2Gy Bone metastasis: 30Gy/3Gy Lung, liver, brain metastases, metastatic lymph nodes: 45Gy/3Gy

Drug:
• Tislelizumab
200 mg IV Q3W
• Cisplatin
During concurrent radiation therapy: 25 mg/m² IV QW During consolidation therapy: 75 mg/m² IV Q3W
• Nab paclitaxel
During concurrent radiation therapy: 75 mg/m² IV QW During consolidation therapy: 220 mg/m² IV Q3W

Locations

Country	Name	City	State
China	Renmin hosptial of Wuhan University	Wuhan	Hubei

Sponsors (1)

Lead Sponsor	Collaborator
Renmin Hospital of Wuhan University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Approximately 40 months from date of the first participant randomization
Secondary	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.	Approximately 40 months from date of the first participant randomization
Secondary	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.	Approximately 40 months from date of the first participant randomization
Secondary	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	Approximately 40 months from date of the first participant randomization
Secondary	Number of participants experiencing Adverse Events (AEs)	AEs are documented according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v4	Approximately 40 months from date of the first participant randomization