Tislelizumab plus chemoradiation with possible surgery for unresectable esophageal squamous cell carcinoma

Phase II Study of Tislelizumab Combined With Induction Chemoradiotherapy and Subsequent Conversion Surgery for Locally Advanced Unresectable ESCC

This trial will try combining Tislelizumab with chemoradiotherapy and, if the tumor becomes operable, surgery for people with locally advanced, unresectable esophageal squamous cell carcinoma to see if it improves 2-year survival.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 45 (estimated)
• Ages: 20 Years and up
• Sex: All
• Sponsor: China Medical University Hospital (other)
• Drugs / interventions: Tislelizumab, chemotherapy
• Locations: 8 sites (Kaohsiung City and 7 other locations)
• Trial ID: NCT07039162 on ClinicalTrials.gov

What this trial studies

This is an open-label, single-arm Phase II study enrolling patients with locally advanced, unresectable esophageal squamous cell carcinoma. Participants receive induction chemoradiotherapy with weekly paclitaxel and cisplatin together with Tislelizumab, followed by two cycles of consolidation Tislelizumab plus chemotherapy. Patients whose tumors convert to resectable status will be offered surgical resection. The primary endpoint is the 2-year overall survival rate, with secondary endpoints including pathological complete response, conversion and R0 resection rates, disease-free and recurrence-free survival, and treatment-related adverse events.

Who should consider this trial

Good fit: Adults aged 20 years or older with histologically confirmed esophageal squamous cell carcinoma that is locally advanced and judged unresectable (e.g., clinical T4 or fixed regional nodes), with ECOG performance status 0–1 and adequate organ function are the ideal candidates.

Not a fit: Patients with non-squamous histology, widespread distant metastases beyond regional nodes, poor performance status, or inadequate organ function are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the regimen could increase the chance that previously unresectable tumors become operable and improve overall survival.

How similar studies have performed: Other trials combining PD-1 inhibitors with chemotherapy or chemoradiation in esophageal cancer have shown promising response and conversion rates, although Tislelizumab-specific data in this exact conversion-to-surgery setting are limited.

Eligibility criteria

Inclusion Criteria:

1. Patients had histologically confirmed, squamous-cell carcinoma of the esophagus
2. Clinical T4 cancer, at least one unresectable metastatic regional lymph node due to invasion into an adjacent organ, or computed tomographic (CT) evidence of M1Lym, such as fixed supraclavicular nodes. Regional lymph nodes are defined on the basis of criteria specified by the eighth edition of the Union for International Cancer Control TNM staging system (Sobin and Wittekind, 2016).
3. An age of at least 20 years
4. An Eastern Cooperative Oncology Group performance-status score 0 or 1
5. Adequate major organ functions

   * WBC ≥3,500/mm3
   * Hemoglobin ≥ 9.0 g/dL
   * Platelet ≥ 80,000/mm3
   * Total bilirubin ≤ 2-fold the upper limit of normal (ULN)
   * ALT and AST ≤ 5-fold the ULN AND ≤200 U/L
   * PT, aPTT and INR ≤1.5-fold the ULN
   * Albumin ≥2.5 g/dL
   * Creatinine clearance ≥50 ml/min (based upon 24 hours urine collection or calculated by Cockroft-Gault formula)

     * Male: ((140 - age) × weight \[kg\])/(72 × serum creatinine \[mg/dL\])
     * Female: 0.85 x estimate for male
6. Women of childbearing potential (including women with chemical menopause or no menstruation for other medical reasons) must agree to use contraception from the time of informed consent until 5 months or more after the last dose of investigational products. (Women of childbearing potential are defined as all women after the onset of menstruation who are not postmenopausal and have not been surgically sterilized (e.g., hysterectomy, bilateral tubal ligation, bilateral oophorectomy). Postmenopause is defined as amenorrhea for ≥12 consecutive months without specific reasons.)
7. Men must agree to use contraception from the start of study treatment until 3 months or more after the last dose of the investigational product.
8. Patients must be willing to undergo definitive resection with lymph node dissection
9. Participants must have signed written informed consent form in accordance with regulatory and institutional guidelines.

Exclusion Criteria:

1. Patient has received systemic therapy for advanced ESCC.
2. Patients had distant metastasis, including liver, lung, bone and brain metastases.
3. Patients had esophageal perforation or esophageal fistula
4. Patients had tumor bleeding
5. Patients had active infection(e.g. tuberculosis).
6. History or known human immunodeficiency virus.
7. Subjects with active, known, or suspected autoimmune disease. Subjects with Type I diabetes mellitus, residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment are permitted to enroll.
8. Systemic immunosuppression therapy or chronic systemic steroid therapy (more than 10mg daily of prednisolone)
9. Known hepatitis B (HBsAg reactive) or C virus infection (positive anti HCV)

   * Inactive hepatitis B surface antigen (HBsAg) carriers, treated and stable hepatitis B (HBV DNA \< 500 IU/mL or \< 2500 copies/mL) can be enrolled. Patients with detectable HBsAg or detectable HBV DNA should be managed per treatment guidelines. Patients receiving antivirals at screening should have been treated for \> 2 weeks before randomization/enrollment.
   * Patients with a positive HCV antibody test followed by a negative HCV RNA test at screening are eligible.
10. Previous therapy targeting T-cell costimulating or immune-checkpoint pathways
11. Prior or concurrent malignancies within the last 3 years, with the exception of carcinoma in situ of the cervix, or basal type skin cancer
12. Any major surgery within 4 weeks before study enrollment.
13. Pregnant women or nursing mothers, or positive pregnancy tests
14. Patients had allogeneic stem cell transplantation or organ transplantation.
15. Has uncontrolled, significant cardiovascular disease or cerebrovascular disease, including NYHA Class III or IV congestive heart failure, unstable angina, myocardial infarction, uncontrolled symptomatic arrhythmia, and/or other serious cardiovascular and cerebrovascular diseases within the 6 months preceding study intervention.
16. Patients with interstitial lung disease, noninfectious pneumonitis, or uncontrolled lung diseases including pulmonary fibrosis, or acute lung diseases
17. Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed.
18. Other patients judged by the investigators be inappropriate as subjects of this study

Where this trial is running

Kaohsiung City and 7 other locations

• Kaohsiung Chang Gung Memorial Hospital — Kaohsiung City, Taiwan (NOT_YET_RECRUITING)
• Kaohsiung Medical University Chung-Ho Memorial Hospital — Kaohsiung City, Taiwan (NOT_YET_RECRUITING)
• China Medical University Hospital — Taichung, Taiwan (RECRUITING)
• Taichung Veterans General Hospital — Taichung, Taiwan (NOT_YET_RECRUITING)
• National Cheng Kung University Hospital — Tainan, Taiwan (NOT_YET_RECRUITING)
• National Taiwan University Hospital — Taipei, Taiwan (NOT_YET_RECRUITING)
• Taipei Veterans General Hospital — Taipei, Taiwan (NOT_YET_RECRUITING)
• Linkou Chang Gung Memorial Hospital — Taoyuan, Taiwan (NOT_YET_RECRUITING)

Study contacts

• Study coordinator: Ming-Yu Lein, MD

Conditions: Esophageal Squamous Cell Carcinoma, Locally Advanced Unresectable Esophageal Cancer