Different Radiation Dose With Concurrent Chemotherapy for Thoracic Esophageal Carcinoma

Study Overview
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Brief Summary
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Definitive chemoradiation is the standard treatment for locally advanced esophageal cancer. NCCN (National Comprehensive Cancer Network) recommends radiation dose of 50-50.4 Gy as the definitive radiation dose for esophageal cancer with definitive chemo-radiation. However, as many studies in China showed that the most common recurrence site after definitive chemo-radiation was within the radiation region. But there have not been large randomized clinical trials to investigate the optimal radiation dose with concurrent chemotherapy for esophageal cancer in China. The purpose of this clinical trial is to investigate the optimal radiation dose for thoracic esophageal squamous cell cancer with definitive concurrent chemoradiotherapy.

Detailed Description
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PRIMARY OBJECTIVES: I. To determine if high-dose radiation with concurrent chemotherapy increases overall survival for thoracic esophageal squamous cell carcinoma SECONDARY OBJECTIVES: I. To evaluate if high-dose radiation with concurrent chemotherapy increased progression-free survival for thoracic esophageal squamous cell carcinoma II.To evaluate if high-dose radiation with concurrent chemotherapy increased local control for thoracic esophageal squamous cell carcinoma OUTLINE: Patients are randomized to one of the two treatment arms ARM 1:Patients receive high-dose radiation with concurrent chemotherapy.High-dose RT:59.4 Gy in 33 fractions, 1.8 Gy per fraction, 5days/week.concurrent chemotherapy: Paclitaxel 50mg/m2 D1+carboplatin AUC (area under curve) =2 D1, weekly for 6 weeks. After that, patients receive consolidative platinum-based 3-week chemotherapy for 2 cycles. ARM 2:Patients receive standard-dose radiation with concurrent chemotherapy.Standard-dose RT:59.4 Gy in 33 fractions, 1.8 Gy per fraction, 5days/week . Concurrent chemotherapy: Paclitaxel 50 mg/m2 D1+carboplatin AUC (area under curve) =2 D1, weekly for 6 weeks. After that, patients receive consolidative platinum-based 3-week chemotherapy for 2 cycles. After completion of study therapy, patients are followed up every 3-4 months for 2 years, then every 6 months for 3 years.

Official Title
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A Multicenter, Prospective, Randomized, Phase III Trial Evaluating High-dose Versus Standard-dose Radiation With Concurrent Chemotherapy for Thoracic Esophageal Squamous Cell Carcinoma

Conditions
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Esophageal Cancer

Intervention / Treatment
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* Radiation: High-dose
* Radiation: Standard-dose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent form Age: 18-75 years Histological or cytologic diagnosis of esophageal squamous cell carcinoma within one month. Clinical stage T1-4 N0-1 M0-1a (AJCC 6th edition）. Supraclavicular lymphatic metastasis or abdominal lymph node metastasis for mid-thoracic also can be included Karnofsky performance status scores: ≥70 Without any prior anticancer therapy BMI≥18kg/m2 or weight loss ≤5% within 3 months Adequate marrow function (within 7 days): White blood cell ≥ 3×109/L,Neutrophils (ANC) ≥1.5×109/L, Platelet count ≥100×109/L, Hemoglobin ≥90g/L. Normal hepatic and renal function (within 14 days): Total bilirubin <1.5 x upper limit of normal (ULN), Alanine aminopeptidase and Aspartase aminotransferase ≤ 2.5 x ULN, creatinine ≤ 1.5xULN Normal cardiac and pulmonary function: Forced expiratory volume at one second (FEV1) ≥1.0 L or FEV1/FVC ≥ 50% pre FEV1; No myocardial infarction within 1 year; no symptomatic heart disease, including myocardial ischemia, congestive heart failure or uncontrolled arrhythmias, roughly normal electrocardiogram; LVEF ≥ 50%，or can receive chemoradiotherapy assessed by cardiologists Exclusion Criteria: Other or mixed pathological type The second primary tumor of esophageal cancer located outside the radiation area Biopsy-proven invasion of the tracheobronchial tree or tracheoesophageal fistula Mid-thoracic esophageal cancer with supraclavicular lymphatic metastasis and abdominal lymph node metastasis; other metastasis Within 2cm of the gastroesophageal junction Prior chemotherapy, prior thoracic radiation, surgical resection or target therapy of the primary tumor Significant medical or psychiatric illnesses that in the physician's judgment (uncontrolled coronary heart disease, cardiomyopathy and/or heart failure requiring hospitalization. Uncontrolled hypertension or history of myocardial infarction within one year. Uncontrolled diabetes mellitus. Acute bacterial or fungal infection requiring intravenous antibiotics. Acute exacerbation of chronic obstructive pulmonary disease (COPD) or other pulmonary disease requiring hospitalization influencing tumor treatment Refused to sign informed consent form Concurrent pregnancy or lactation History of a second malignancy other than nonmelanoma skin cancer, and cervical cancer in situ.

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
Interventional Model Description: High dose radiation plus chemotherapy of paclitaxel and carboplatin vs standard dose radiation plus chemotherapy of paclitaxel and carboplatin.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High-dose<br>concurrent chemoradiotherapy High-dose RT:59.4 Gy in 33 fractions, 1.8 Gy per fraction, 5days/week; CT: Paclitaxel 50 mg/m2 D1+carboplatin AUC (area under curve) =2 D1, weekly for 6 weeks. After that, patients receive consolidative platinum-based 3-week chemotherapy for 2 cycles. | Radiation: High-dose<br>* Drug: concurrent chemotherapy with radiation paclitaxel plus carboplatin are used weekly in both arms<br>|
| Active Comparator: Standard-dose<br>concurrent chemoradiotherapy Standard-dose RT:50.4 Gy in 28 fractions, 1.8Gy per fraction, 5days/week; CT: Paclitaxel 50 mg/m2 D1+carboplatin AUC (area under curve) =2 D1, weekly for 6 weeks. After that, patients receive consolidative platinum-based 3-week chemotherapy for 2 cycles. | Radiation: Standard-dose<br>* Drug: concurrent chemotherapy with radiation paclitaxel plus carboplatin are used weekly in both arms<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival |  | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival |  | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Esophageal cancer, radiation, chemotherapy