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

Phase 3

Recruiting

• Conditions: Esophageal Cancer
• Interventions: Procedure: esophagectomy; Combination Product: chemoradiation; Other: active surveillance

• Registration Number: NCT04135664
• Lead Sponsor: Shanghai Chest Hospital

Brief Summary

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

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.

Study Timeline

• Status Verified: 2019-08
• Study Start: 2019-09-01
• Study First Submitted: 2019-10-09
• Study First Submitted QC: 2019-10-20
• Last Update Submitted: 2019-10-20
• Study First Posted: 2019-10-22
• Last Update Posted: 2019-10-22
• Primary Completion: 2027-12-01
• Study Completion: 2027-12-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 176

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Prospective registry of patients that cannot be randomized	esophagectomy	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.
Patients undergoing adjuvant esophagectomy	esophagectomy	Patients underwent endoscopic submucosal dissection and diagnosed with pathological-T1b and clinical-N0 squamous cell carcinoma. Patients randomized into undergoing adjvant esophagectomy.
Prospective registry of patients that cannot be randomized	chemoradiation	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.
Patients undergoing adjuvant chemoradiation	chemoradiation	Patients underwent endoscopic submucosal dissection and diagnosed with pathological-T1b and clinical-N0 squamous cell carcinoma. Patients randomized into undergoing adjvant chemoradiation.
Prospective registry of patients that cannot be randomized	active surveillance	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.

Primary Outcome Measures

Name	Time	Method
5-year overall survival rate	5 years after enrollment day	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.

Secondary Outcome Measures

Name	Time	Method
3-year overall survival rate	3 years after enrollment day	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.
Quality of life differences (EORTC QLQ-OES18)	1st, 3rd, 6th, 12th and 24th month after enrollment	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.
3-year relapse free survival rate	3 years after enrollment day	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-year relapse free survival rate	5 years after enrollment day	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.
Quality of life differences (EORTC QLQ-C30)	1st, 3rd, 6th, 12th and 24th month after enrollment	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.

Trial Locations

Locations (6)

The First Affiliated Hospital of Nanchang University; 🇨🇳 Nanchang, Jiangxi, China

Changhai Hospital, The Second Military Medical University; 🇨🇳 Shanghai, China

Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine; 🇨🇳 Shanghai, China

Shanghai Chest Hospital, Shanghai Jiao Tong University; 🇨🇳 Shanghai, China

Zhongshan Hospital, Fudan University; 🇨🇳 Shanghai, China

Tianjin Medical University Cancer Institute and Hospital; 🇨🇳 Tianjin, China