Role of Esophagectomy in Complete Responders to CCRT

Study Overview
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Brief Summary
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To investigate the role of esophagectomy in complete responders to preoperative chemoradiotherapy for squamous cell carcinoma of esophagus, patients will be randomized to either observation or esophagectomy after concurrent chemoradiotherapy.

Detailed Description
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After completion of concurrent chemoradiotherapy, patients will be reassed and visited to multidisciplinary clinic, then, randomized to either observation or esophagectomy.

Official Title
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A Randomized Phase III Trial on the Role of Esophagectomy in Complete Responders to Preoperative Chemoradiotherapy for Squamous Cell Carcinoma of Esophagus

Conditions
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Esophageal Squamous Cell Carcinoma

Intervention / Treatment
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* Procedure: esophagectomy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically proven squamous cell carcinoma of the intrathoracic esophagus Surgically resectable (cT3, cT4a and/or disease with lymph node metastasis by AJCC 7th ed) esophageal cancer, as determined by Endoscopic Ultra Sound (EUS), chest CT and PET-CT No prior treatment for the esophageal cancer Age: 20-70 years ECOG performance status 0, 1 or 2 Adequate hematological, renal, hepatic, pulmonary and cardiac functions defined as 6.1 Granulocytes > 1,500/microliter, Platelets > 75,000/microliter 6.2 Creatinine < 1.5 mg/dL (or CCr> 50 mg/mL), 6.3 Total bilirubin < 1.5 mg/dL 6.4 ALT and AST < 2.5 × upper normal limit 6.5 FEV1 >=1.5 L/min 6.6 Ejection fraction >= 45% Non-pregnant, non-lactating female patients. Sexually active patients of childbearing potential must implement effective contraceptive practices during the study when treated with chemotherapy Written, voluntary informed consent Exclusion Criteria: Subtypes other than squamous cell carcinoma cT1N0M0, cT2N0M0 esophageal cancer or in situ carcinoma Invasion of recurrent laryngeal, phrenic or sympathetic nerve Invasion of the tracheobronchial tree or presence of tracheoesophageal fistula Invasion of major vessels (vena cava, azygos vein and aorta) by the tumor Malignant pleural effusion (documented by cytospin or cytology) Cervical esophageal cancer Para-aortic lymph node metastasis Past or current history of malignancy other than entry diagnosis except for non-melanomatous skin cancer, curatively treated carcinoma in situ of the cervix, curatively treated early gastric cancer with endoscopic mucosal resection or a cured malignancy more than 5 years prior to enrollment Previous chemotherapy or prior history of radiotherapy interfering with the planned radiotherapy as per protocol Patients with a known history of HIV seropositivity or HCV (+). Patients with HBV (+) are eligible. However, primary prophylaxis using antiviral agents (i.e. lamivudine, etc) is recommended for HBV carrier to prevent HBV reactivation during whole treatment period. Other serious illness or medical conditions A. Unstable cardiac disease (i.e. congestive heart failure, arrhythmia, symptomatic coronary artery disease) despite treatment, myocardial infarction within 6 months prior to study entry B. History of significant neurologic or psychiatric disorders including dementia or seizures C. Active uncontrolled infection (viral, bacterial or fungal infection) D. Other serious medical illnesses New York heart Association Class III/IV and history of active angina. Documented myocardial infarction within the 6 months preceding registration. Patients with a history of significant ventricular arrhythmia requiring medication or congestive heart failure. History of 2nd or 3rd degree heart blocks. Active infection or other serious underlying medical condition which would impair the ability of the patient to receive the planned treatment Dementia or altered mental status that would prohibit the understanding and giving of informed consent Uncontrolled diabetes mellitus: fasting glucose >150 mg/dL or patients requiring insulin therapy for glycemic control; fasting glucose >150 mg/dL or patients requiring insulin therapy for glycemic control;

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 70 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Arm B: observation:<br>No additional treatment after concurrent chemoradiotherapy. However, esophagectomy will be considered as a salvage treatment for local recurrence during observation. | |
| Experimental: Arm A: esophagectomy<br>Esophagectomy will be performed preferentially within 8 weeks (maximum 12 weeks) after completion of concurrent chemoradiotherapy | Procedure: esophagectomy<br>* esophagectomy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 2-year disease-free survival (DFS) rate |  | 2 years from the enrollment of last patient | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) |  | 5 years from the enrollment of last patient | 
| progression-free survival |  | 5 years from the enrollment of last patient | 
| failure pattern |  | 5 years from the enrollment of last patient | 
| Number of Participants with Adverse Events |  | up to 60 days after treatment | 
| Comparison of clinical complete response (cCR) vs. pathologic complete response rate (pCR) in patients who underwent esophagectomy |  | 5 years | 
| Comparison of OS according to clinical response (CR vs PR vs SD/PD) after preoperative chemoradiotherapy among those who underwent preplanned esophagectomy; |  | 5 years from the enrollment of the last patient | 
| Comparison of OS according to metabolic response after induction chemotherapy |  | 5 years from the enrollment of the last patient | 
| Quality of life |  | 5 years from the enrollment of the last patient | 
| Comparison of PFS according to clinical response (CR vs PR vs SD/PD) after preoperative chemoradiotherapy among those who underwent preplanned esophagectomy; |  | 5 years from the enrollment of the last patient | 
| Comparison of TTF according to clinical response (CR vs PR vs SD/PD) after preoperative chemoradiotherapy among those who underwent preplanned esophagectomy; |  | 5 years from the enrollment of the last patient | 
| Comparison of PFS according to metabolic response after induction chemotherapy |  | 5 years from the enrollment of the last patient | 
| Comparison of TTF according to metabolic response after induction chemotherapy |  | 5 years from the enrollment of the last patient | 
| treatment-related mortality |  | up to 60 days after completion of treatment |