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

Sponsor

Shanghai Chest Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT04135664

Collaborator

(none)

176

Enrollment

Locations

Arms

Anticipated Duration (Months)

29.3

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Esophageal Cancer	Procedure: esophagectomy Combination Product: chemoradiation Other: active surveillance	Phase 3

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 Design

Study Type:

Interventional

Anticipated Enrollment :

176 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Participant)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Sep 1, 2019

Anticipated Primary Completion Date :

Dec 1, 2027

Anticipated Study Completion Date :

Dec 1, 2027

Arms and Interventions

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

Arm

Intervention/Treatment

Active Comparator: Patients undergoing adjuvant esophagectomy

Patients underwent endoscopic submucosal dissection and diagnosed with pathological-T1b and clinical-N0 squamous cell carcinoma. Patients randomized into undergoing adjvant esophagectomy.

Procedure: esophagectomy

esophagectomy with at least two-field (thoracic-abdominal) lymphadenectomy

Experimental: Patients undergoing adjuvant chemoradiation

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

concurrent chemotherapy and radiotherapy

Active Comparator: Prospective registry of patients that cannot be randomized

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

esophagectomy with at least two-field (thoracic-abdominal) lymphadenectomy

Combination Product: chemoradiation

concurrent chemotherapy and radiotherapy

Other: active surveillance

No further adjuvant therapy

Outcome Measures

Primary Outcome Measures

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

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.
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.
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The First Affiliated Hospital of Nanchang University	Nanchang	Jiangxi	China	JX 791
2	Changhai Hospital, The Second Military Medical University	Shanghai		China	SH 21
3	Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine	Shanghai		China	SH 21
4	Shanghai Chest Hospital, Shanghai Jiao Tong University	Shanghai		China	SH 21
5	Zhongshan Hospital, Fudan University	Shanghai		China	SH 21
6	Tianjin Medical University Cancer Institute and Hospital	Tianjin		China