Study of Neo-adjuvant Chemoradiotherapy Followed by Minimally Invasive Esophagectomy for Squamous Cell Esophageal Cancer

Study Overview
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Brief Summary
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The primary objective is to compare neo-adjuvant chemoradiotherapy followed by Mckeown Minimally Invasive Esophagectomy (MIE) Versus Mckeown MIE, pure radical chemoradiotherapy in terms of the overall survival time (OS) in patients with Stage IIB or III squamous cell esophageal carcinoma.

Detailed Description
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Esophageal cancer is one of the most difficult malignancies to cure. Surgical resection remains the primary treatment for localized esophageal cancer. It increases the chances of cure and alleviates the symptoms of dysphagia compared with nonoperative methods. Advances in surgical techniques and equipments have made minimally invasive esophagectomy (MIE) more popular and wider application since 1990s. During the past two decades, MIE has progressively been accepted as an alternative treatment for esophageal cancer around the world. The prognosis has some improvement on account of these significant advances in surgical techniques and perioperative management, But the prognosis of patients with locally advanced esophageal cancer remains rather poor. As a result of surgery alone, the 5-year survival rate of about 25% has not changed significantly in several decades. Preoperative chemoradiotherapy followed by surgery seems to hopefully improve the survival of EC. Nevertheless, the results of different studies were inconsistent. Recently, the CROSS trial has demonstrated that preoperative chemoradiotherapy can significantly increased the overall survival of patients with EC compared with surgery alone. It should be noticed that only 84 cases(23%) of ESCC were enrolled in this trial with potential minimal follow-up of 2 years, which may be not perfect to evaluate the effect of this combined therapy for this tumor type. Based on our preliminary study, we have demonstrated the validity and safety of vinorelbine and cisplatin-based neoadjuvant chemoradiotherapy. Then we are to carry out a clinical trial to investigate the effect of this multidisciplinary therapy, by comparing neo-adjuvant chemoradiotherapy followed by Mckeown MIE versus Mckeown MIE, pure radical chemoradiotherapy in terms of the overall survival time (OS) in patients with Stage IIB or III squamous cell esophageal carcinoma.

Official Title
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A Single Institution Prospective Randomized Controlled Clinical Trial of Neo-adjuvant Chemoradiotherapy Followed by Mckeown Minimally Invasive Esophagectomy (MIE) Versus Mckeown MIE for Locally Advanced Squamous Cell Esophageal Carcinoma

Conditions
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Squamous Cell Esophageal Carcinoma

Intervention / Treatment
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* Procedure: Neo-adjuvant Chemoradiotherapy followed by Mckeown MIE
* Drug: Cisplatin
* Device: Mckeown MIE


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologic diagnosis of squamous cell thoracic esophageal carcinoma of Stage IIB or III, which is potentially resectable. Patients must not have received any prior anticancer therapy. More than 6 months of expected survival. Age ranges from 18 to 70 years. Absolute white blood cells count ≥4.0×109/L, neutrophil ≥1.5×109/L, platelets ≥100.0×109/L, hemoglobin ≥90g/L, and normal functions of liver and kidney. Karnofsky performance status (KPS) of 90 or more. Signed informed consent document on file. Exclusion Criteria: Patients are diagnosed or suspected to be allergic to cisplatin or vinorelbine. Patients with concomitant hemorrhagic disease. Pregnant or breast feeding. Inability to use gastric conduit after esophagectomy because of a prior surgery. Patients with concomitant peripheral neuropathy, whose CTC status is 2 or even more. Have a prior malignancy other than esophageal carcinoma, carcinoma in situ of the cervix, nonmelanoma skin cancer or cured early stage of prostate cancer.

Ages Eligible for Study
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Minimum Age: 18 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: experimental group<br>Neo-adjuvant Chemoradiotherapy followed by Mckeown MIE | Procedure: Neo-adjuvant Chemoradiotherapy followed by Mckeown MIE<br>* Neo-adjuvant Chemoradiotherapy followed by Mckeown MIE<br>|
| Active Comparator: Radical Chemoradiotherapy<br>only Radical Chemoradiotherapy | Drug: Cisplatin<br>* only Radical Chemoradiotherapy<br>* Other names: vinorelbine;|
| Active Comparator: Mckeown MIE<br>only Mckeown MIE | Device: Mckeown MIE<br>* only Mckeown MIE using thoracoscopy and laparoscopy<br>* Other names: Laparoscopy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival rate |  | 1 years | 
| Disease free survival |  | 5years | 
| Overall survival rate |  | 3years | 
| Overall survival rate |  | 5years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the opportunity of MIE after neo-adjuvant chemoradiotherapy | Criteria:Response Evaluation Criteria in Solid Tumors，RECIST | 4 weeks after completion of radiotherapy | 
| Side effects of neo-adjuvant chemoradiotherapy | Evaluate the toxicities of neo-adjuvant chemoradiotherapy,according to National Cancer Institute Common Terminology Criteria for Adverse Event,Version 3.0 | 2 weeks after completion of radiotherapy | 
| Duration of surgery | The time between the start of surgery until the end of surgery | Intraoperative | 
| Quantity of bleeding | The amount of bleeding during surgery | Intraoperative | 
| number of lymph nodes retrieved | The total number of lymph nodes obtained including cervix area, mediastinum area , abdominal area | Intraoperative | 
| Days of postoperative stay | Participants will be followed for the duration of hospital stay after surgery, an expected average of 12 days | The duration of hospital stay after surgery, an expected average of 12 days | 
| Rate of Operative Complication |  | 30 days after surgery | 
| Mortality of perioperation |  | 30 days after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Squamous Cell Esophageal Carcinoma, minimally invasive esophagectomy, laparoscopy, thoracoscopy