Tislelizumab Combined With Neoadjuvant Radiotherapy and Chemotherapy for Resectable Esophageal Squamous Cell Carcinoma.

Neoadjuvant Tislelizumab Combined With Chemoradiotherapy for Resectable Locally Advanced Esophageal Squamous Cell Carcinoma : Single Arm Phase II Study

This study aimed to evaluate the safety and feasibility of neoadjuvant tislelizumab combined with chemoradiotherapy in patients with resectable esophageal squamous cell cancer. The tumor microenvironment and circulating immunological biomarkers in these patients were further evaluated to explore the factors affecting the efficacy of neoadjuvant therapy for esophageal cancer. This study will provide valuable information for further prospective clinical trials of neoadjuvant anti-PD-1 and other immunotherapy in esophageal cancer patients.

Study Overview

• Status: Recruiting
• Conditions: Advanced Esophageal Squamous Cell Cancer
• Intervention / Treatment: Drug: Tislelizumab Combined With Neoadjuvant Radiotherapy and Chemotherapy

• Study Type: Interventional
• Enrollment (Anticipated): 15
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shandong
    • Jinan, Shandong, China, 250117
      • Recruiting
      • Shandong Cancer Hospital and Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 18-75
2. Histologically or cytologically confirmed resectable squamous-cell esophageal cancer ( cT1-2N+/ cT3-4aN0-3M0)
3. Eastern Cooperative Oncology Group (ECOG) status 0-1
4. Signed written informed consent prior to the implementation of any trial-related rocedures
5. Adequate organ function, evidenced by laboratory results with no contraindications to chemotherapy Absolute neutrophil count ≥ 1,500 х109/l Thrombocytes ≥ 100 х 109/l Hemoglobin ≥ 90 mg/l Creatinine ≤ 1.5 x ULN or creatinine clearance (calculated using the Cockcroft-Gault formula) ≥40 mL/min Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) > 2.5 x upper limit of normal (ULN) Alkaline phosphatase (ALP) > 5 x ULN Bilirubin > 1.5 х ULN

Exclusion Criteria:

1. Patients diagnosed with any other malignant tumor
2. Patients at risk for tracheoesophageal fistula or aortoesophageal fistula
3. Have received prior therapy with: chemotherapy, radiation therapy,immune checkpoint inhibitor
4. Insufficient caloric and/or fluid intake despite consultation with a dietitian and/or tube feeding
5. Have an active infection requiring systemic therapy that has not resolved 3 days (simple infection, such as cystitis) to 7 days (severe infection, such as pyelonephritis) before the first dose of trial treatment
6. Patients who cannot tolerate chemoradiotherapy or surgery due to severe cardiac, lung dysfunction
7. A history of interstitial lung disease or non-infectious pneumonia
8. Active autoimmune disease with systemic therapy (ie, use of disease modifiers, corticosteroids, or immunosuppressive drugs) in the past 2 years
9. Known history of human immunodeficiency virus (HIV) infection (i.e., positive for HIV 1/2 antibody) and various viral hepatitis infections
10. Patients who have received allogeneic stem cell or solid organ transplantation
11. Women during pregnancy or lactation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tislelizumab arm; Radiotherapy: PTV 41.4Gy in 23 Fractions，5 days per week; Chemotherapy: Paclitaxel (Albumin bound) (100mg/m2) and Cisplatin (75 mg/m2) for 5 weeks, concurrent with radiotherapy; Immunotherapy: Tislelizumab (200mg per 3 weeks)	Drug: Tislelizumab Combined With Neoadjuvant Radiotherapy and Chemotherapy; Patients received tislelizumab at a fixed dose of 200 mg every three weeks (q3w, 21 days) for 2 cycles.; Other Names: Anti-PD-1 Therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major Pathological Response Rate	No more than 10% of tumor cells were found in neoadjuvant surgical specimens.	From date of surgery to 14 days later
Pathologic complete response rate	Pathologic complete response rate	From date of surgery to 14 days later

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease free survival	Disease free survival will be calculated from the start of the treatment to the disease progression or death of any reason.	24 months
Incidence of Treatment-related Adverse Events	Number and percentage of cases of all adverse events	8 weeks

Collaborators and Investigators

• Sponsor: Shandong Cancer Hospital and Institute

Study record dates

Study Major Dates

• Study Start (Actual): April 20, 2022
• Primary Completion (Anticipated): October 20, 2023
• Study Completion (Anticipated): October 20, 2024

Study Registration Dates

• First Submitted: April 5, 2022
• First Submitted That Met QC Criteria: April 11, 2022
• First Posted (Actual): April 12, 2022

Study Record Updates

• Last Update Posted (Actual): March 14, 2023
• Last Update Submitted That Met QC Criteria: March 11, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Esophageal Neoplasms; Carcinoma, Squamous Cell; Esophageal Squamous Cell Carcinoma; Neoplasms, Squamous Cell
• Other Study ID Numbers: Shandong CHI

Drug and device information, study documents

• 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.: Yes