Comparative analysis of patients with resectable locally advanced esophageal squamous cell carcinoma treated with neoadjuvant chemotherapy or neoadjuvant chemoradiotherapy combined sintilimab versus neoadjuvant chemoradiotherapy.
The research process is divided into three stages: firstly, the stage of screening period for 14 days. Qualified subjects will enter the treatment period after completion of screening examination and evaluation. And then, the stage of treatment period: Experimental group (group A) received sintilimab combined with neoadjuvant chemotherapy regimen: preoperative neoadjuvant, sintilimab (D1 administration) combined with chemotherapy (TP regimen: albumin-paclitaxel + carboplatin, D1 administration) for 2 cycles. Every 3 weeks, there was a dosing cycle (Q3W). The experimental group (group B) received neoadjuvant sintilimab combined concurrent chemoradiotherapy: preoperative sintilimab (D1 administration) combined with neoadjuvant concurrent chemoradiotherapy. Chemotherapy regimen: TP regimen: albumin-paclitaxel + carboplatin, D1 administration, 2 cycles. Every 3 weeks, there was a dosing cycle (Q3W). Radiotherapy regimen: according to IMRT treatment plan, the total dose was 41.4Gy, divided into 23 times, 5 days a week. And the control group (group C) received neoadjuvant chemoradiotherapy and the regimen was similar with group B. Surgery was performed 6-8 weeks after completion of neoadjuvant therapy. If the patient without vital tumor cells in primary and lymph nodes after surgery, they only need regular follow-up visit. If the patients with non-pCR resected, those patients need to receive adjuvant immunotherapy. And if the patients with non-R0 resected, the regimen of those patients need to carefully decide based on multidisciplinary team discussed. Lastly, the stage of postoperative assistance, the researchers selected postoperative treatment according to the guidelines for the diagnosis and treatment of esophageal cancer. Patients were followed up for efficacy and safety within 90 days after surgery, once every 3 months for 2 years and once every 6 months for 2-5 years.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
420
Sintilimab: D1 administration) for 2 cycles. Every 3 weeks was a dosing cycle (Q3W)
Radiotherapy: According to IMRT treatment plan, the total dose was 41.4Gy, divided into 23 times, 5 days a week.
Neoadjuvant chemotherapy with TP regimen: albumin-paclitaxel + carboplatin, D1 administration) for 2 cycles. Every 3 weeks was a dosing cycle (Q3W).
Sichuan Cancer Hospital and Research Institute
Chengdu, Sichuan, China
Pathology complete response rate, pCR
Definition of pathology complete response is "no cancer cell, including lympho nodes" which corresponds with tumor regression score 0 definition of pathologic response is as follows. Tumor regression score Grade 0 and 1 will be defined as "responder" and 2 and 3 will be considered as "non-responders".
Time frame: 3 months after the surgery
Treatment related adverse event, TRAE
The TRAE defined as the proportion of participants who have treatment-related adverse events assessed by National Cancer Institute Common Terminology Criteria for Adverse Event, Version 4.0 (CTCAE v4.0).
Time frame: 3 months after the surgery
Major Pathological Remission rate, MPR
The residual tumor after neoadjuvant treatment ≤ 10% residual tumor lesion in surgical specimen compared to baseline.
Time frame: 3 months after the surgery
Rate of R0 resection
Measure the rate of R0 resection with all margins microscopically clear.
Time frame: 3 months after the surgery
Events Free Survival, EFS
Event-free survival was defined as the time from the date of randomization to the date of the first documented non-fatal event (worsening cardiac function, hospitalization for congestive heart failure, liver function impairment, liver cirrhosis, transformation to AML, as defined in the protocol), or death, whichever occurred first. Participants who did not experience a non-fatal event as of the time of data cut-off (end of study), as well as participants who did not experience a non-fatal event and stopped study participation before the data cut-off, were censored as specified in the protocol.
Time frame: Through study completion, an average of 1 year.
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Overall Survival,OS
Overall survival was the duration from the start of study treatment to death.
Time frame: 5 years after inclusion
disease-free survival, DFS
DFS is defined as the time interval between the date of random assignment and the date of the first documented evidence of relapse at any site or death related to cancer (including toxicity), whichever occurred first.
Time frame: 5 years after inclusion
Disease Control Rate, DCR
he Disease Control Rate (DCR) will be defined as the proportion of patients with a best overall response of CR, PR or Stable Disease (SD) (RECIST V1.1) 2 months after randomization
Time frame: 3 years after inclusion
Objective Response Rate, ORR
The Objective Response Rate (ORR) will be defined as the proportion of patients with a best overall response of Complete Response (CR) or Partial Response (PR) (RECIST V1.1)
Time frame: 3 years after inclusion
Circulating tumor DNA, ctDNA
Blood will be drawn and tested for ctDNA
Time frame: Before neoadjuvant therapy, before surgery, 1, 6, 12, 18, 24 months after surgery