This is a prospective, single-arm phase II clinical trial intended to investigate the efficacy of neoadjuvant CTLA-4 monoclonal antibody combined with PD-1 monoclonal antibody plus preoperative chemoradiotherapy for locally advanced esophageal cancer. A total of 44 patients with resectable esophageal squamous cell carcinoma (ESCC) will be enrolled.All enrolled subjects will receive induction therapy with the combination of a CTLA-4 inhibitor and a PD-1 inhibitor. Three weeks afterwards, patients will transition to concurrent chemoradiotherapy combined with PD-1 inhibitor. Intensity-modulated radiotherapy (IMRT) will be delivered at a total dose of 40 Gy in 20 fractions. Radical esophagectomy with two-field thoracic and abdominal lymph node dissection will be performed 6-8 weeks after completion of chemoradiotherapy.The primary objective of this trial is to evaluate the efficacy and safety of the triplet regimen consisting of CTLA-4 inhibitor plus PD-1 inhibitor combined with preoperative chemoradiotherapy in locally advanced esophageal cancer, so as to further optimize the multimodal therapeutic strategy for esophageal cancer.
This is a single-arm, phase II, single-center clinical trial enrolling patients with resectable locally advanced thoracic esophageal squamous cell carcinoma (ESCC) staged as T1-4aN1-3M0 or T3-4aN0M0 per the 8th edition of the UICC TNM staging system. A total of 51 subjects are planned for enrollment. Patients will receive neoadjuvant concurrent chemoradiotherapy combined with dual immune checkpoint blockade (anti-CTLA-4 plus anti-PD-1 monoclonal antibodies) to evaluate the efficacy and safety of this regimen. Treatment Regimens Chemotherapy and dual immunotherapy agents Anti-CTLA-4 monoclonal antibody (IBI310): 1 mg/kg via intravenous infusion on Day 1 (D1);Anti-PD-1 monoclonal antibody (sintilimab): 200 mg per administration via intravenous infusion on D1, D22 and D43;Nab-paclitaxel: 75 mg/m² via intravenous infusion on D22, D29, D36 and D43;Cisplatin: 25 mg/m² via intravenous infusion on D22, D29, D36 and D43. Radiotherapy Intensity-modulated radiotherapy (IMRT) is delivered at a total dose of 40 Gy in 20 fractions (40 Gy/20 f), initiated on D22 with 5 fractions per week to be completed within 4 weeks. Surgery Preoperative re-evaluation is scheduled at 6-8 weeks after completion of neoadjuvant chemoradiotherapy plus dual immunotherapy. Patients without surgical contraindications will undergo radical esophagectomy plus two-field (thoracoabdominal) lymph node dissection.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
51
Chemotherapy and dual immunotherapy agents Anti-CTLA-4 monoclonal antibody (IBI310): 1 mg/kg via intravenous infusion on Day 1 (D1);
Sintilimab (anti-PD-1 monoclonal antibody) will be administered at a dose of 200 mg via intravenous infusion on Day 1, Day 22 and Day 43.
Nab-paclitaxel: 75 mg/m² via intravenous infusion on D22, D29, D36 and D43; Cisplatin: 25 mg/m² via intravenous infusion on D22, D29, D36 and D43.
Intensity-modulated radiotherapy (IMRT) will be adopted with a total dose of 40 Gy in 20 fractions. Radiotherapy starts on Day 22, administered 5 times per week and completed within 4 weeks.
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Guangzhou, Guangdong, China
RECRUITINGPathologic complete response rate
No malignant tumor cells were detected in the removed specimens including primary tumor and lymph nodes
Time frame: Two weeks after surgery
R0 resection rate
The persentage of patients who under complete resection
Time frame: Two weeks after surgery
Tumor Regression Grade
Time frame: Two weeks after surgery
Progression free survival
Progression free survival is defined as the time from randomization until objective tumor progression or death
Time frame: At end of enrollment-up to 5 years in follow up
Overall survival
Overall survival will be calculated from the date of randomization and an event registered on the date of death from those with no death recorded on the day the database is frozen,will be censored on the date of last follow up
Time frame: At the end of enrollment-up to 5 years in follow up
Incidence of perioperative complications
Incidence of complications
Time frame: Ninety days after surgery
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