Conversion of Tislelizumab Combined With Chemotherapy in Unresectable Esophageal Squamous Cell Carcinoma

Phase 2

Recruiting

• Conditions: Unresectable; Esophageal Squamous Cell Carcinoma by AJCC V8 Stage
• Interventions: Drug: tislelizumab+ Paclitaxel + Cisplatin

• Registration Number: NCT05449483
• Lead Sponsor: Tianjin Medical University Cancer Institute and Hospital

Brief Summary

Whether the introduction of immunotherapy can transform unresectable esophageal cancer into resectable, or even achieve R0 surgical resection, has not been reported yet. We plan to conduct a prospective, single-center, single-arm phase II clinical study of the safety and efficacy of tislelizumab combined with chemotherapy in the treatment of unresectable esophageal squamous cell carcinoma.

Detailed Description

For patients not eligible for R0 resection (defined as locally advanced unresectable esophageal cancer), preoperative treatment can theoretically transform the tumor into a resectable state. The current significance of transformation therapy is to reduce tumor volume and stage to achieve radical resection, eliminate micrometastases, and prevent a postoperative recurrence. There are few studies on the transformation therapy of esophageal squamous cell carcinoma. We plan to conduct a prospective, single-center, single-arm phase II clinical study of the safety and efficacy of tislelizumab combined with chemotherapy in the treatment of T4a/N3 esophageal squamous cell carcinoma.

Study Timeline

• Study Start: 2022-05-11
• Status Verified: 2022-07
• Study First Submitted: 2022-07-04
• Study First Submitted QC: 2022-07-07
• Last Update Submitted: 2022-07-07
• Study First Posted: 2022-07-08
• Last Update Posted: 2022-07-08
• Primary Completion: 2023-06-30
• Study Completion: 2025-06-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

1. Histologically confirmed esophageal squamous cell carcinoma;
2. Unresectable cT4a/N3(stage ⅣA) (AJCC 8 TNM classification);
3. Have a performance status of 0 or 1 on the ECOG Performance Scale;
4. Age 18-75 years old, both men and women;
5. Be willing and able to provide written informed consent/assent for the trial;
6. Demonstrate adequate organ function, all screening labs should be performed within 10 days of treatment initiation;
7. Female subjects of childbearing potential should have a negative urine or serum pregnancy within 72 hours before receiving the study medication's first dose. If the urine test is positive or cannot be confirmed as unfavorable, a serum pregnancy test will be required;
8. Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion through repeated biopsies. Newly acquired is defined as a specimen obtained up to 4 weeks (28 days) prior to initiation of treatment on Day 1. Subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen only upon agreement from the Sponsor.

Exclusion Criteria

1. Prior therapy (operation, radiotherapy, immunotherapy, or chemotherapy) for esophageal cancer;
2. Ineligibility or contraindication for esophagectomy;
3. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug;
4. Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with the use of disease-modifying agents, corticosteroids, or immunosuppressive drugs);
5. Has severe hypersensitivity and adverse events (≥Grade 3) to any PD-1/PD-L1 inhibitors.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
tislelizumab+ Paclitaxel+Cisplatin	tislelizumab+ Paclitaxel + Cisplatin	Paclitaxel 135mg/m2 , D1; Cisplatin 80mg/m2, D1; tislelizumab 200mg D2 ; totally 2-4 cycles

Primary Outcome Measures

Name	Time	Method
R0 Surgical Resection Rate .	1 year	R0 resection rate

Secondary Outcome Measures

Name	Time	Method
Evaluate the rate of pathologic complete response (pCR) to the study regimen	1 year	The percentage of pathologic complete response at resection for patients who has completed the study regimen
Evaluate the rate of main pathologic response (MPR) to the study regimen.	1 year	Viable tumor comprised ≤ 10% of resected tumor specimens
Overall survival (OS)	3 years	Time from the enrollment to death of any cause
Objective response rate (ORR)	1 year	Partial response is defined as a decrease by 30% or more in sums of longest diameter of measurable target lesions
Disease-free survival (DFS)	3 years	DFS is defined as the time interval between the date of enrollment and the date of the first documented evidence of relapse after radical resection at any site or death related to cancer

Trial Locations

Locations (1)

Hongjing Jiang; 🇨🇳 Tianjin, Tianjin, China