Esophageal squamous cell carcinoma
Conditions
Interventions
Control group:Two cycles of anti–PD-1 therapy (tislelizumab) combined with chemotherapy as neoadjuvant treatment
Experimental group:Two cycles of low-dose radiotherapy (total dose 16 Gy in 8 fractions) combined with anti–PD-1 therapy (tislelizumab) and chemotherapy as neoadjuvant treatment
Sponsors
West China Hospital of Sichuan University
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: (1) Histologically (pathologically) confirmed thoracic esophageal squamous cell carcinoma with clinical stage: cT1b–cT2N1–3M0 or cT3–cT4aN0–3M0 (AJCC/UICC 8th edition staging system for esophageal cancer); (2) Eligible for R0 radical resection; (3) ECOG performance status score 0–1; (4) Age >=18 years and =3.5 × 10?/L; absolute neutrophil count (ANC) >=1.5 × 10?/L; platelet count (PLT) >=100 × 10?/L; hemoglobin (HGB) >=9 g/dL; (6) Assessed by a radiation oncologist as having no severe pulmonary ventilatory dysfunction or acute heart failure. Pulmonary function requirements: FEV1/FVC >=70%; FEV1 >=50% of predicted value; DLCO (diffusing capacity of the lung for carbon monoxide), measured value as a percentage of predicted value >80%; (7) Liver function: total bilirubin (TBIL) =30 g/L; (8) Renal function: serum creatinine =60 mL/min (calculated using the Cockcroft/Gault formula): Female: CrCl = (140 - age) × weight (kg) × 0.85 ÷ [72 × serum creatinine (mg/dL)] Male: CrCl = (140 - age) × weight (kg) × 1.00 ÷ [72 × serum creatinine (mg/dL)]; (9) Voluntarily agrees to participate in the study, signs a written informed consent form, and is able to comply with the protocol-specified visit schedule and related study procedures during the study period; (10) Expected survival >6 months; (11) Agrees to undergo surgery and neoadjuvant multimodality therapy (including radiotherapy, chemotherapy, and immunotherapy); (12) Women of childbearing potential must undergo a pregnancy test within 7 days prior to initiation of treatment, with a negative result. All study participants (regardless of sex) must use appropriate contraception during the study period and for 8 weeks after the last administration of the study drug; (13) No evidence of esophageal perforation or active esophageal bleeding, and no invasion of the trachea or major thoracic vessels; (14) At least one measurable lesion according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Exclusion criteria
Exclusion criteria: (1) Unsuitable for protocol-specified immunotherapy or chemotherapy; (2) Prior treatment for ESCC, including investigational products, chemotherapy, radiotherapy, or prior therapy with anti-PD-1, anti-PD-L1, anti-PD-L2 antibodies, or any other agents targeting T-cell co-stimulatory or checkpoint pathways; (3) History of fistula caused by primary tumor invasion; (4) Patients assessed by the investigator as having a high risk of fistula or signs of perforation; (5) Any condition requiring systemic corticosteroid therapy (prednisone >10 mg/day or equivalent) or other immunosuppressive therapy within 14 days prior to the first dose. Exceptions include: 1) Adrenal replacement steroids (prednisone <=10 mg/day or equivalent); 2) Topical, ophthalmic, intra-articular, intranasal, or inhaled corticosteroids with minimal systemic absorption; 3) Short-term (<=7 days) use of corticosteroids for prophylaxis or treatment of non-autoimmune conditions; 4) Dexamethasone as premedication for paclitaxel-based chemotherapy; (6) Active autoimmune disease or a history of autoimmune disease with potential for recurrence. Participants meeting the following conditions may be eligible: 1) Well-controlled type 1 diabetes mellitus; 2) Hypothyroidism requiring only hormone replacement therapy; 3) Well-controlled celiac disease; 4) Skin disorders not requiring systemic treatment (e.g., vitiligo, psoriasis, or alopecia); 5) Autoimmune diseases not expected to recur in the absence of external triggers; (7) History of interstitial lung disease, non-infectious pneumonitis, or poorly controlled pulmonary diseases (including pulmonary fibrosis, acute lung disease, etc.); (8) Infections requiring systemic antibacterial, antifungal, or antiviral therapy, including active tuberculosis; Severe infection within 4 weeks prior to the first dose, including but not limited to infection-related complications requiring hospitalization, bacteremia, or severe infectious pneumonia; Therapeutic oral or intravenous antibiotics within 2 weeks prior to the first dose; (9) Known history of allogeneic organ transplantation (except corneal transplantation) or allogeneic hematopoietic stem cell transplantation; (10) Known hypersensitivity to tislelizumab or to the active ingredients or excipients of the combined chemotherapy drugs; (11) Clinically significant and symptomatic abnormalities in rhythm, conduction, or morphology on resting electrocardiogram (ECG), such as complete left bundle branch block, second-degree or higher atrioventricular block, ventricular arrhythmias, or atrial fibrillation; unstable angina; congestive heart failure; or chronic heart failure of New York Heart Association (NYHA) class =2.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pathological Complete Response rate; | — |
Secondary
| Measure | Time frame |
|---|---|
| Event-Free Survival;Major Pathological Response rate;R0 resection rate;Objective Response Rate;Overall Survival;Safty; | — |
Countries
China
Contacts
Public ContactYong Yuan
West China Hospital of Sichuan University
Outcome results
None listed