Esophageal Squamous Cell Carcinoma Stage II, Esophageal Squamous Cell Carcinoma Stage III
Conditions
Keywords
Esophageal Squamous Cell Carcinoma
Brief summary
The purpose of this study was to evaluate the safety, feasibility and outcome of anti-PD-1 antibody (Tislelizumab, BeiGene) combined with neoadjuvant chemoradiotherapy versus neoadjuvant chemoradiotherapy followed by minimally invasive esophagectomy for locally advanced resectable esophageal squamous cell carcinoma (cII-III Stage) patient.
Detailed description
It is a prospective randomized phase II&III clinical trial sponsored by Shanghai Zhongshan Hospital with other twelve hospitals in China participating in. 476 patients with locally advanced resectable esophageal squamous cell carcinoma (cII-III Stage) are recruited and randomly assigned into the neoadjuvant chemoradiotherapy combined with immunotherapy group (nCRT plus anti-PD-1 Group) and the neoadjuvant chemoradiotherapy group (nCRT Group) according to the proportion of 1:1. The safety, efficacy of protocols and prognosis of patients are compared between the two regimens.
Interventions
PROCEDURENeoadjuvant Chemoradiotherapy
Chemotherapy: carboplatin (AUC 2 mg/mL per min) and paclitaxel (50 mg/m2 of body-surface area) were administered intravenously for five cycles, starting on days 1, 8, 15, 22, and 29. For each cycle, Carboplatin and paclitaxel were administered 30 minutes apart. Radiotherapy: A total radiation dose of 41.4 Gy was given in 23 fractions of 1.8 Gy, 5 days per week (Radiotherapy was performed on the 2nd, 3rd, 4th, 5th, and 6th day in each cycle, and only 3 times in the 5th cycle)
DRUGTislelizumab
Tislelizumab (200mg/time) was administered intravenously on the 1st and 22nd day. The intravenous injection lasts about 30 minutes (micropump is recommended, intravenous bolus is prohibited, duration should be not less than 20 minutes and not more than 60 minutes);
PROCEDUREIvor-Lewis or Mckeown Esophagectomy(Mckeown Esophagectomy recommended)
After neoadjuvant therapy, patients in groups receive Ivor-Lewis or Mckeown Esophagectomy (Mckeown Esophagectomy recommended)
Sponsors
Peking University Cancer Hospital & Institute
Shanghai Chest Hospital
First Affiliated Hospital of Wenzhou Medical University
Tianjin Medical University Cancer Institute and Hospital
Ningbo Medical Center Lihuili Hospital
The First People's Hospital of Changzhou
Zhongshan Hospital (Xiamen), Fudan University
Xuhui Central Hospital, Shanghai
Shanghai Minhang Central Hospital
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Zhejiang Cancer Hospital
Sichuan Cancer Hospital and Research Institute
Tongji Hospital
Sun Yat-sen University
Shanghai Fifth People's Hospital
Shanghai Zhongshan Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Histologically-confirmed esophageal squamous cell carcinoma and whose tissue samples were taken before treatment; 2. Tumors of the esophagus are located in the thoracic cavity; 3. Pre-treatment stage as clinical II-III (AJCC/UICC 8th Edition) 4. Age is between 18 years and 75 years; 5. Eastern Cooperative Oncology Group (ECOG) performance status 0-1, and expected survival time ≥12 months; 6. Adequate cardiac function. All patients should perform ECG, and those with a cardiac history or ECG abnormality should perform echocardiography with the left ventricular ejection fraction \> 50 %; 7. Adequate respiratory function with FEV1≥1.2L, FEV1%≥50% and DLCO≥50% shown in pulmonary function tests ; 8. Adequate bone marrow function (White Blood Cells \>4x10\^9 /L; Neutrophil \>2.0×10\^9 /L; Hemoglobin \> 90 g/L; platelets\>100x10\^9 /L); 9. Adequate liver function (Total bilirubin \<1.5x Upper Level of Normal (ULN); Aspartate transaminase(AST) and Alanine transaminase (ALT) \<1.5x ULN); 10. Adequate renal function (Glomerular filtration rate (CCr) \>60 ml/min; serum creatinine (SCr) ≤120 µmol/L); 11. The patient has provided written informed consent and is able to understand and comply with the study;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pathological response rate(pCR) | Up to the date of pathological reports obtained since the date of randomization, up to 12 months | The resected specimen following neo-adjuvant treatment are assessed by using standardized work up of the resection specimen in the pathology department and standardized histological criteria for tumor regression grading. The degree of histomorphologic regression is clarified into four categories as follows: grade 1, no evidence of vital residual tumor cells (pathological complete response); grade 2, less than 10% vital residual tumor cells; grade 3, 10 to 50%; and grade 4, more than 50%. |
| Overall survival(OS) | Up to the date of death of any causes since the date of randomization, up to 36 months | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| R0 resection rate | Up to the date of pathological reports obtained since the date of randomization, up to 12 months | No vital tumor is presented at the proximal, distal, or circumferential resection margin, it is considered to be R0 resection. If a vital tumor is shown at 1 mm or less from the proximal, distal, or circumferential resection margin, it is considered to be microscopically positive (R1). |
| Number and Location of positive lymph nodes | Up to the date of pathological reports obtained since the date of randomization, up to 12 months | According to pathological reports, record the number and location of positive lymph nodes |
| Overall Quality of life | Up to the end of follow-up since the data of surgery, up to 36 months | Overall Quality of life is respectively evaluated at randomization and 1 month, 3 month, 6 month and yearly after surgery among patients by using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C-30 Scale (EORTC QLQ-C30) |
| Treatment related complications | Up to 1 month after surgery since the data of randomization, up to 13 months | Number and severity of adverse events that are related to treatment of each patients (including adverse events associated with neoadjuvant chemoradiotherapy, immunotherapy(irAE) and surgery), and hospital re-admission. Treatment-related adverse events as assessed by CTCAE v5.0 |
| Recurrence-free survival (RFS) | Up to the date of disease recurrence since the date of surgery, up to 36 months | RFS is defined in resected patients who achieved an R0 or R1 resection as the time interval from surgery to the date of first recurrence (local, regional or distant) or death, whichever comes first. |
| Correlation between genetic profile and tumor response | Up to the end of follow-up since the data of surgery, up to 36 months | Genetic profile (assessed by whole exome sequencing, T-cell receptor sequencing, RNA sequencing) .illumina HiSeq and Nanostring platforms will be used to evaluate the patient's genetic profile. The tumor response will be evaluated by an experienced thoracic tumor pathologist in our center through Tumor regression grading (TRG) systems. |
| Quality of life in eating and swallowing function | Up to the end of follow-up since the data of surgery, up to 36 months | Quality of life in eating and swallowing function is respectively evaluated at randomization and 1 month, 3 month, 6 month and yearly after surgery among patients by using the EORTC QLQ-OES18 Scale |
| Progression-free survival(PFS) | Up to the date of disease recurrence since the date of randomization, up to 36 months | Disease recurrence is defined as locoregional (esophageal bed or anastomotic or regional lymph nodes) or metastatic (supraclavicular lymph nodes or distant organs) |
Countries
China
Outcome results
None listed