Effective systemic therapy such as nivolumab as an adjuvant therapy has been demonstrated to improve the outcomes of patients receiving neoadjuvant chemoradiotherapy (CRT) for locoregional esophageal cancer. A more effective systemic therapy with anti-PD-1 or anti-PD-L1 immune checkpoint inhibitors (ICIs) plus cisplatin-based doublet chemotherapy, which has shown with high tumor response rate and improved survivals in patients with late-stage ESCC, may provide crucial benefit to patients with locally advanced disease by improving the systemic control, downstaging the locoregional tumor burden and reducing recurrence and metastasis. Collectively, the investigators hypothesize that total neoadjuvant therapy (TNT) approach-consisting of induction immunochemotherapy followed by CRT-is a promising strategy to enhance the outcomes for participants with locally advanced esophageal squamous cell carcinoma.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
50
200 mg, 1h-IVF, Q3W on day 1 for 2 cycles
Paclitaxel 175 mg/m2, 3h-IVF, Q3W on day 1 for 2 cycles
Cisplatin 75 mg/m2, 2h-IVF, Q3W on day 1 for 2 cycles
Chemoradiotherapy * Paclitaxel 50 mg/m2, 1h-IVF, on days 1, 8,15, 22, and 29; * Cisplatin 30 mg/m2,1h-IVF, on days 1, 8,15, 22, and 29; * RT: 1.8 Gy/fraction, 5 days a week, for 25 fractions (total dose= 45 Gy).
National Taiwan University Hospital
Taipei, Taiwan
RECRUITINGpathological complete response
To evaluate the pathological complete response (pCR) rate of participants receiving total neoadjuvant therapy with induction immunochemotherapy and chemoradiotherapy (CRT) followed by surgery in operable ESCC.
Time frame: through study completion, an average of 6 months
Major pathological response
defined as number of participants with residual tumor cells ≤10% at the time of surgery divided by the number of participants received esophagectomy
Time frame: through study completion, an average of 6 months
R0 resection rate
defined as number of participants with no gross residual disease, plus negative section margins (i.e., proximal, distal, and circumferential margins are all \> 1 mm) according to pathological examination of esophagectomy specimen.
Time frame: through study completion, an average of 6 months
Disease-free survival
defined as the time from esophagectomy until evidence of disease recurrence or death in participants received esophagectomy.
Time frame: from esophagectomy until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 50 months
Event-free survival
defined as the time from enrollment to an event which may include radiographic progression, clinical progression, local or distant recurrence, second aerodigestive tract squamous cell carcinoma, and death.
Time frame: from enrollment to an event which may include radiographic progression, clinical progression, local or distant recurrence, second aerodigestive tract squamous cell carcinoma, and death from any cause, whichever came first, assessed up to 50 months
Distant metastasis-free survival
defined as the time from esophagectomy until evidence of distant metastasis recurrence or death.
Time frame: from esophagectomy until evidence of distant metastasis recurrence or death from any cause, whichever came first, assessed up to 50 months
Overall survival
defined as the time from enrollment to death.
Time frame: the time from enrollment to death from any cause, whichever came first, assessed up to 50 months
Loco-regional recurrence rate
defined as number of participants with loco-regional recurrence divided by the number of participants received esophagectomy
Time frame: from esophagectomy until evidence of loco-regional metastasis recurrence or death from any cause, whichever came first, assessed up to 50 months
Distant metastasis rate
defined as number of participants with distant recurrence divided by the number of participants received esophagectomy
Time frame: from esophagectomy until evidence of distant metastasis or death from any cause, whichever came first, assessed up to 50 months
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