Comparison Between NCRT and NCT Followed by MIE for Treatment of Locally Advanced Resectable ESCC

Not Applicable

Completed

• Conditions: Esophageal Squamous Cell Carcinoma Stage cT3-4aN0-1M0
• Interventions: Procedure: Neoadjuvant Chemoradiotherapy; Procedure: Neoadjuvant Chemotherapy; Procedure: Minimally Invasive Esophagectomy

• Registration Number: NCT03001596
• Lead Sponsor: Shanghai Zhongshan Hospital

Brief Summary

The purpose of this study is to evaluate the outcomes of neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy followed by minimally invasive esophagectomy on patients with locally advanced resectable esophageal squamous cell carcinoma(cT3-4aN0-1M0).

Detailed Description

It is a prospective randomized phase III clinical trial sponsored by Shanghai Zhongshan Hospital with other eight hospitals in China participating in. 264 patients with locally advanced resectable esophageal squamous cell carcinoma(cT3-4aN0-1M0) are recruited and randomly assigned into the neoadjuvant chemoradiotherapy group (NCRT group) and the neoadjuvant chemotherapy group (NCT group) according to the proportion of 1:1.The safety,efficacy of protocols and prognosis of patients are compared between the two regimens.

Study Timeline

• Study First Submitted: 2016-12-17
• Study First Submitted QC: 2016-12-22
• Study First Posted: 2016-12-23
• Study Start: 2017-01
• Primary Completion: 2019-02
• Study Completion: 2020-08
• Status Verified: 2020-09
• Last Update Submitted: 2020-09-07
• Last Update Posted: 2020-09-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 264

Inclusion Criteria

1. Histologically-confirmed squamous cell carcinoma of the esophagus;
2. Tumors of the esophagus are located in the thoracic cavity;
3. Pre-treatment stage as cT3-4aN0-1M0 (AJCC/UICC 7th Edition) (In case of stage cT4a, curative resectability has to be explicitly verified by the local surgical investigator prior to randomization).
4. Age is between 18 years and 75 years,
5. Eastern Cooperative Oncology Group (ECOG) performance status 0-1;
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;

Exclusion Criteria

1. Patients with non-squamous cell carcinoma histology;
2. Patients with advanced inoperable or metastatic esophageal cancer;
3. Pre-treatment stage as cT1-2N0-1M0 (AJCC/UICC 7th Edition);
4. Pre-treatment stage as cN2-3 or cT4b(non-curatively-resectable verified by the local surgical investigator, AJCC/UICC 7th Edition);
5. Patients with another previous or current malignant disease which is likely to interfere with treatment or the assessment of response in the judgement of the local surgical investigator.
6. Any patient with a significant medical condition which is thought unlikely to tolerate the therapies. Such as cardiac disease (e.g. symptomatic coronary artery disease or myocardial infarction within last 12 months), clinically-significant lung disease, clinically-significant bone marrow, liver, renal function disorder;
7. Pregnant or lactating women and fertile women who will not be using contraception during the trial;
8. Allergy to any drugs;
9. Participation in another intervention clinical trial with interference to the chemotherapeutic or chemoradiotherapeutic intervention during this study or during the last 30 days prior to informed consent;
10. Expected lack of compliance with the protocol.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Neoadjuvant chemoradiotherapy	Minimally Invasive Esophagectomy	Neoadjuvant chemoradiotherapy (NCRT) is performed followed by minimally invasive esophagectomy in enrolled patients.
Neoadjuvant chemotherapy	Minimally Invasive Esophagectomy	Neoadjuvant chemotherapy (NCT) is performed followed by minimally invasive esophagectomy in enrolled patients.
Neoadjuvant chemoradiotherapy	Neoadjuvant Chemoradiotherapy	Neoadjuvant chemoradiotherapy (NCRT) is performed followed by minimally invasive esophagectomy in enrolled patients.
Neoadjuvant chemotherapy	Neoadjuvant Chemotherapy	Neoadjuvant chemotherapy (NCT) is performed followed by minimally invasive esophagectomy in enrolled patients.

Primary Outcome Measures

Name	Time	Method
Overall survival(OS)	Up to the date of death of any causes since the date of randomization, up to 36 months

Secondary Outcome Measures

Name	Time	Method
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).
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 standardised work up of the resection specimen in the pathology department and standardised histological criteria for tumour 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%.
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).
Positive lymph nodes' number	Up to the date of pathological reports obtained since the date of randomization, up to 12 months	According to pathological reports, record the number of positive lymph nodes
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, and hospital readmission.
Quality of life(QOL)	Up to the end of follow-up since the data of surgery, up to 36 months	QOL 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 (EORTC QLQ-C30) and EORTC QLQ-OES18
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.

Trial Locations

Locations (1)

Shanghai Zhongshan Hospital; 🇨🇳 Shanghai, Shanghai, China