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Sintilimab Plus NCT or NCRT Versus NCRT for ESCC

Phase 3
Not yet recruiting
Conditions
Esophageal Squamous Cell Carcinoma
Interventions
Drug: Chemotherapy
Radiation: radiotherapy
Registration Number
NCT05244798
Lead Sponsor
Sichuan Cancer Hospital and Research Institute
Brief Summary

Comparative analysis of patients with resectable locally advanced esophageal squamous cell carcinoma treated with neoadjuvant chemotherapy or neoadjuvant chemoradiotherapy combined sintilimab versus neoadjuvant chemoradiotherapy.

Detailed Description

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.

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
All
Target Recruitment
420
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Group of sintilimab combined with neoadjuvant chemotherapyChemotherapysintilimab (D1 administration) was given in combination with chemotherapy (TP regimen: albumin-paclitaxel + carboplatin, D1 administration) for 2 cycles. Every 3 weeks, there was a dosing cycle (Q3W). Surgery was performed 6-8 weeks after completion of neoadjuvant therapy. If the patients 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.
Group of sintilimab combined with neoadjuvant chemoradiotherapyradiotherapysintilimab (D1) was administered in combination with 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. Surgery was performed 6-8 weeks after completion of neoadjuvant therapy. If the patients 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.
Group of sintilimab combined with neoadjuvant chemoradiotherapyChemotherapysintilimab (D1) was administered in combination with 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. Surgery was performed 6-8 weeks after completion of neoadjuvant therapy. If the patients 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.
Group of neoadjuvant chemoradiotherapyradiotherapyThe control group received neoadjuvant chemoradiotherapy and the regimen was as follows: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. Surgery was performed 6-8 weeks after completion of neoadjuvant therapy. If the patients 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.
Group of neoadjuvant chemoradiotherapyChemotherapyThe control group received neoadjuvant chemoradiotherapy and the regimen was as follows: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. Surgery was performed 6-8 weeks after completion of neoadjuvant therapy. If the patients 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.
Group of sintilimab combined with neoadjuvant chemotherapySintilimabsintilimab (D1 administration) was given in combination with chemotherapy (TP regimen: albumin-paclitaxel + carboplatin, D1 administration) for 2 cycles. Every 3 weeks, there was a dosing cycle (Q3W). Surgery was performed 6-8 weeks after completion of neoadjuvant therapy. If the patients 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.
Group of sintilimab combined with neoadjuvant chemoradiotherapySintilimabsintilimab (D1) was administered in combination with 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. Surgery was performed 6-8 weeks after completion of neoadjuvant therapy. If the patients 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.
Primary Outcome Measures
NameTimeMethod
Pathology complete response rate, pCR3 months after the surgery

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".

Secondary Outcome Measures
NameTimeMethod
Treatment related adverse event, TRAE3 months after the surgery

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).

disease-free survival, DFS5 years after inclusion

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.

Major Pathological Remission rate, MPR3 months after the surgery

The residual tumor after neoadjuvant treatment ≤ 10% residual tumor lesion in surgical specimen compared to baseline.

Rate of R0 resection3 months after the surgery

Measure the rate of R0 resection with all margins microscopically clear.

Events Free Survival, EFSThrough study completion, an average of 1 year.

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.

Overall Survival,OS5 years after inclusion

Overall survival was the duration from the start of study treatment to death.

Disease Control Rate, DCR3 years after inclusion

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

Objective Response Rate, ORR3 years after inclusion

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)

Circulating tumor DNA, ctDNABefore neoadjuvant therapy, before surgery, 1, 6, 12, 18, 24 months after surgery

Blood will be drawn and tested for ctDNA

Trial Locations

Locations (1)

Sichuan Cancer Hospital and Research Institute

🇨🇳

Chengdu, Sichuan, China

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