Esophageal squamous cell carcinoma
Conditions
Interventions
Early Group:Sliburumab 4.5mg/kg + Albumin-bound paclitaxel 125mg/m2 (D1, D8) + Cisplatin 75mg/m2 (D1), all infusions completed before 12:00
Mid-day Group:Sliburumab 4.5mg/kg + Albumin-bound paclitaxel 125mg/m2 (D1, D8) + Cisplatin 75mg/m2 (D1), infusion started after 12:00 and completed before 15:00
Late Group:Sliburumab 4.5mg/kg + Albumin-bound paclitaxel 125mg/m2 (D1, D8) + Cisplatin 75mg/m2 (D1), infusion started at or after 15:00
Sponsors
Tangdu Hospital, Air Force Medical University
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Voluntarily provide written informed consent and agree to participate in this study. 2. Histologically or cytologically confirmed esophageal squamous cell carcinoma. 3. Thoracic esophageal cancer evaluated by CT/MRI/EUS with clinical stage T1b-4aN+M0 or T2-4N0M0 (T2N0 patients must have high-risk factors: lymphovascular invasion [LVI], tumor size >=3 cm, or poor differentiation), according to the 8th edition of AJCC staging system. 4. Expected to be eligible for R0 resection. 5. Age 18–75 years, male or female. 6. ECOG performance status 0–1 (see Appendix 1). 7. No prior anti-tumor therapy for esophageal cancer, including radiotherapy, chemotherapy, surgery, etc. 8. Planned to undergo surgical resection after completion of neoadjuvant therapy. 9. No contraindications to surgery. 10. Adequate organ function, defined as: (1) Hematology (no blood products, colony-stimulating factors, leukocyte-elevating agents, platelet-elevating agents or anti-anemia agents within 14 days before first study drug administration): Absolute neutrophil count >=1.5×10^9/L; platelet count >=100×10^9/L; hemoglobin >=90 g/L. (2) Blood biochemistry: Total bilirubin =50 mL/min. (3) Coagulation: International normalized ratio (INR) <=1.5×ULN; activated partial thromboplastin time (APTT) <=1.5×ULN. 11. Female subjects of childbearing potential must have a negative serum pregnancy test within 72 hours before first study drug administration, and use effective contraception during the study and for at least 3 months after last administration (e.g., intrauterine device, contraceptive pills, condoms). Male subjects with female partners of childbearing potential must be surgically sterile or agree to use effective contraception during the study and for 3 months after last administration. 12. Completion of the Morningness-Eveningness Questionnaire (MEQ) before enrollment. 13. Agree to undergo biopsy at baseline, provide tumor tissue samples at surgery, and cooperate with 5 longitudinal blood collections throughout the study (baseline, on-treatment, pre-surgery, post-surgery follow-up) for biomarker analysis. 14. Good compliance, able to adhere to the follow-up schedule and regular assessments, and strictly comply with the randomly assigned treatment time windows (morning, midday, or evening).
Exclusion criteria
Exclusion criteria: 1. Obvious invasion of adjacent organs (aorta or trachea) by the tumor. 2. Presence of supraclavicular lymph node metastasis. 3. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage. 4. Poor nutritional status with BMI 10 mg/day prednisone or equivalent) within 2 weeks before first study drug administration. Inhaled or topical steroids and physiological replacement doses of corticosteroids are permitted in the absence of active autoimmune disease. (3) Live attenuated vaccines within 4 weeks before first study drug administration. (4) Major surgery or severe trauma within 4 weeks before first study drug administration. 7. Any active or history of autoimmune disease, including but not limited to interstitial pneumonia, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism. Patients with controlled hypothyroidism on hormone replacement may be considered. Patients with fully resolved psoriasis or childhood asthma/allergies requiring no adult intervention may be included; those requiring medical intervention with bronchodilators are excluded. 8. History of immunodeficiency, including positive HIV test, other acquired or congenital immunodeficiency disorders, organ transplantation, or allogeneic bone marrow transplantation. 9. Uncontrolled cardiac conditions, including but not limited to: (1) Heart failure >= NYHA class II; (2) Unstable angina; (3) Myocardial infarction within 1 year; (4) Clinically significant supraventricular or ventricular arrhythmias that are untreated or poorly controlled. 10. Severe infection (CTCAE grade >2) within 4 weeks before first study drug administration, such as severe pneumonia, bacteremia, infectious complications requiring hospitalization. Active pulmonary inflammation on baseline chest imaging, or signs/symptoms of infection requiring oral or intravenous antibiotics within 14 days before first study drug administration (prophylactic antibiotics excluded). 11. Active pulmonary tuberculosis confirmed by medical history or CT scan, history of active tuberculosis within 1 year before enrollment, or history of active tuberculosis more than 1 year previously without standard treatment. 12. Active hepatitis B (HBV DNA >=2000 IU/mL or 10^4 copies/mL) or hepatitis C (positive anti-HCV antibody with detectable HCV RNA above the lower limit of quantification). 13. Diagnosis of another malignancy within 5 years before first study drug administration, except for adequately treated malignancies with very low metastatic or mortality risk (5-year survival >90%), such as basal cell carcinoma, squamous cell carcinoma of the skin, or carcinoma in situ of the cervix. 14. Pregnant or lactating female subjects. 15. Any other conditions judged by the investigator that may lead to premature study discontinuation, including other severe diseases (including psychiatric disorders), alcoholism, drug abuse, social or family factors th
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pathological Complete Response, pCR; | — |
Secondary
| Measure | Time frame |
|---|---|
| Major Pathological Response (MPR);Event-Free Survival, EFS;Overall Survival, OS;R0 resection rate;Treatment-related adverse events;Objective Response Rate, ORR; | — |
Countries
China
Contacts
Public ContactYan Xiaolong
Tangdu Hospital,Air Force Medical University
Outcome results
None listed