Comparison of Esophagectomy and Chemoradiation for Patients With cN0-pT1b Stage Esophageal Squamous Cell Carcinoma

Study Overview
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Brief Summary
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The ad-ESD trial is phase III randomized trial to compare adjuvant esophagectomy and chemoradiation for patients with clinical stage N0 and pathological stage T1b squamous cell carcinoma (after endoscopic submucosal dissection).

Detailed Description
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Esophagectomy is still the primary treatment for pathological T1b esophageal squamous cell carcinoma. However, esophagectomy is associated with high mortality and morbidity and decreased quality of life. Endoscopic resection followed with chemoradiation had showed uncompromised oncological outcomes with esophagectomy. But there is no well-designed, phase III trial to compare the two treatment for patients with pT1b squamous cell carcinoma. The ad-ESD trial is a multi-center prospective superiority trial, combied of a randomized clinical trial and a prospective registry. The experimental design produces two randomized arms; (1) esophagectomy and (2) chemoradiation. An additional registry arm will be based on surgeons/patients that do not want to be randomised because of their own experience on adjuvant therapy, including esophagectomy; chemoradiation and active surveillance. The primary endpoint is to evaluate the difference of 5-year overall survival rate between definitive chemoradiation and esophagectomy, in patients with cN0-pT1b esophageal squamous cell cancer (ESCC) after endoscopic resection. The secondary endpoints are to evaluate the difference of quality of life and oncological outcomes including 3-year overall survival (OS) and 3, 5-year relapse free survival (RFS) between the two treatments.

Official Title
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Adjuvant Esophagectomy Versus Chemoradiation for Patients With Clinical Stage N0 and Pathological Stage T1b (After Endoscopic Submucosal Dissection, ESD) Esophageal Squamous Cell Carcinoma (Ad-ESD Trial): a Multicentric, Open Label, Randomized Trial

Conditions
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Esophageal Cancer

Intervention / Treatment
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* Procedure: esophagectomy
* Combination Product: chemoradiation
* Other: active surveillance


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Biopsy proven with esophageal squamous cell cancer. Clinical N0 stage diagnosed by imaging examinations. Pathological T1b stage confirmed by endoscopic submucosal dissection. Age: 18-75. Tumor located at the thorax. Performance status Eastern Cooperative Oncology Group (ECOG) performance status 0-1. Written informed consent. Exclusion Criteria: Prior intervention treatment before endoscopic submucosal resection. Inability to accept any treatment component. Prior intervention (surgery, chemoradiation, et al.) for other primary tumor disease. Distant metastasis. The circumference of the lumen over 3/4 Main tumor size > 5cm assessed by endoscopy Inability to understand the informed consent.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Patients undergoing adjuvant esophagectomy<br>Patients underwent endoscopic submucosal dissection and diagnosed with pathological-T1b and clinical-N0 squamous cell carcinoma. Patients randomized into undergoing adjvant esophagectomy. | Procedure: esophagectomy<br>* esophagectomy with at least two-field (thoracic-abdominal) lymphadenectomy<br>|
| Experimental: Patients undergoing adjuvant chemoradiation<br>Patients underwent endoscopic submucosal dissection and diagnosed with pathological-T1b and clinical-N0 squamous cell carcinoma. Patients randomized into undergoing adjvant chemoradiation. | Combination Product: chemoradiation<br>* concurrent chemotherapy and radiotherapy<br>|
| Active Comparator: Prospective registry of patients that cannot be randomized<br>Patients underwent endoscopic submucosal dissection and diagnosed with pathological-T1b and clinical-N0 squamous cell carcinoma. Patients cannot be randomized into undergoing adjvant esophagectomy or chemoradiaton. This arm includes patients undergoing adjuvant esophagectomy; adjuvant chemoradiation and active surveillance. | Procedure: esophagectomy<br>* esophagectomy with at least two-field (thoracic-abdominal) lymphadenectomy<br>Combination Product: chemoradiation<br>* concurrent chemotherapy and radiotherapy<br>Other: active surveillance<br>* No further adjuvant therapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 5-year overall survival rate | The overall survival is defined as days from date of randomization to death from any cause, and cencored at the last day of follow up when patients are alive. | 5 years after enrollment day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 3-year overall survival rate | The overall survival is defined as days from date of randomization to death from any cause, and cencored at the last day of follow up when patients are alive. | 3 years after enrollment day | 
| 3-year relapse free survival rate | The relapse free survival is defined as days from date of randomization until the date of tumor progression or the date of death causing of any reasons, and cencored at the last day of follow up when patients are alive. | 3 years after enrollment day | 
| 5-year relapse free survival rate | The relapse free survival is defined as days from date of randomization until the date of tumor progression or the date of death causing of any reasons, and cencored at the last day of follow up when patients are alive. | 5 years after enrollment day | 
| Quality of life differences (EORTC QLQ-C30) | The quality of life will be assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Cancer patients (EORTC QLQ-C30) questionnaire. Patients will be invited to finish the questionnaire at the day of recruitment, 1st, 3rd, 6th, 12th and 24th month after randomization. | 1st, 3rd, 6th, 12th and 24th month after enrollment | 
| Quality of life differences (EORTC QLQ-OES18) | The quality of life will be assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Cancer patients (EORTC QLQ-OES18) questionnaire. Patients will be invited to finish the questionnaire at the day of recruitment, 1st, 3rd, 6th, 12th and 24th month after randomization. | 1st, 3rd, 6th, 12th and 24th month after enrollment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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esophagectomy, chemoradiation, esophageal cancer, endoscopic submucosal dissection