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

NCT05919030 | Recruiting Phase 3 DMC

• 1 other identifier: WDRY2023-K088
• Study Type: interventional
• Target: 155
• Locations: 1 country
• Sites: 1

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.

Conditions

Esophageal Squamous Cell Carcinoma

Keywords

Chemoradiation; Immunotherapy; Advanced esophageal cancer; Low PD-L1 expression; Progression-free survival

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Overall Survival (OS)

  Approximately 40 months from date of the first participant randomization

• Objective Response Rate (ORR)

  Approximately 40 months from date of the first participant randomization

• Duration of Response (DOR)

  Approximately 40 months from date of the first participant randomization

• Number of participants experiencing Adverse Events (AEs)

  Approximately 40 months from date of the first participant randomization

Study Arms (2)

Chemoradiation + Tislelizumab

EXPERIMENTAL

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

Radiation: Intensity-modulated radiotherapy (IMRT); Drug: Tislelizumab; Drug: Cisplatin; Drug: Nab paclitaxel

Chemotherapy + Tislelizumab

ACTIVE COMPARATOR

Drug: Tislelizumab 200 mg IV Q3W Drug: Nab Paclitaxel 220 mg/m² IV Q3W Drug: Cisplatin 75 mg/m² IV Q3W

Drug: Tislelizumab; Drug: Cisplatin; Drug: Nab paclitaxel

Interventions

Intensity-modulated radiotherapy (IMRT) RADIATION

Esophageal primary tumor: 39.6Gy/2.2Gy Bone metastasis: 30Gy/3Gy Lung, liver, brain metastases, metastatic lymph nodes: 45Gy/3Gy

Chemoradiation + Tislelizumab

Tislelizumab DRUG

200 mg IV Q3W

Chemoradiation + Tislelizumab; Chemotherapy + Tislelizumab

Cisplatin DRUG

During concurrent radiation therapy: 25 mg/m² IV QW During consolidation therapy: 75 mg/m² IV Q3W

Chemoradiation + Tislelizumab; Chemotherapy + Tislelizumab

Nab paclitaxel DRUG

During concurrent radiation therapy: 75 mg/m² IV QW During consolidation therapy: 220 mg/m² IV Q3W

Chemoradiation + Tislelizumab; Chemotherapy + Tislelizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Renmin Hospital of Wuhan University: lead

Study Sites (1)

Renmin hosptial of Wuhan University

Wuhan, Hubei, 430060, China

RECRUITING

MeSH Terms

Conditions

Esophageal Squamous Cell Carcinoma

Interventions

Radiotherapy, Intensity-Modulated; tislelizumab; Cisplatin; Taxes

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Esophageal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Economics; Health Care Economics and Organizations

Central Study Contacts

Yongshun Chen, MD

CONTACT

+86 15327122084; yongshun2007@163.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 16, 2023
• First Posted: June 26, 2023
• Study Start: July 1, 2023
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2027
• Last Updated: November 14, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)