Phase II/III Study Compare Adjuvant Chemoradiotherapy, Radiotherapy and Surgery Alone for Esophageal Carcinoma

Study Overview
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Brief Summary
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This phase III trial is studying how well the combination of chemoradiation or radiation works in resected locally advanced cancer of the esophagus or gastroesophageal junction.

Detailed Description
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Although preoperative chemoradiation therapy followed by surgery is the most common approach for patients with resectable esophageal cancer, considerable number of esophageal cancer patients received operation as the first treatment modality. Accordingly, postoperative treatments have always been playing an important role because of the poor survival rates of the patients in stage ⅡB[UICC 7th edition] -Ⅲ[UICC 7th edition] who have been treated with resection alone. The existing data shows that the 5-yeal survival rate of stageⅡB-Ⅲ of thoracic esophageal squamous cell carcinoma(TESCC) after surgery is merely about 28.4% ,and locoregional lymph nodes metastases is responsible for the main cause of failure. While we have proved the value of prophylactic radiation therapy after radical esophagectomy for esophageal carcinoma with positive lymph node metastases and stage Ⅲ disease (UICC 6th edition) under the conventional 2-dimensional radiotherapy methods in subset analysis of prospective randomized clinical trial. For patients with positive lymph nodes, 5 year survival after surgery alone was 28.4%, median overall survival was 24 months, recurrence patterns were 34.6% in mediastinal lymph nodes，13.3% in supraclavicular lymph nodes，10% in abdominal lymph nodes. Distant metastases occurred in 21% patients. Adjuvant radiotherapy significantly reduced the recurrence in mediastinal lymph nodes(13.4%), supraclavicular lymph nodes (6.1%). However distant metastases rate increased to 30.7%. Chemotherapy may be vital for these patients. Chen reported that 5 year overall survival rates for the chemoradiotherapy group and radiotherapy group were 47.4% and 38.6% (P=0.03). Based on our studies, treatment failure occurred in 8% patients because of celiac metastases. Small radiation field by omitting celiac drainage region may ensure patients to accept 2 cycles of concurrent chemotherapy for lower toxicity.

Official Title
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A Phase II/III Study of Adjuvant Chemoradiotherapy, Radiotherapy After Surgery Versus Surgery Alone in Patients With Stage ⅡB-Ⅲ Esophageal Carcinoma

Conditions
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Esophageal Neoplasms, Esophageal Cancer

Intervention / Treatment
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* Radiation: Adjuvant Chemoradiation
* Radiation: Adjuvant Radiation
* Drug: Paclitaxel
* Drug: Cisplatin or Nedaplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: KPS≥70 Diagnosis of stage ⅡB or Ⅲ thoracic esophageal cancer Complete resection Adequate organ function: Hematopoietic Absolute granulocyte count at least 1,500/mm^3 Platelet count at least 150,000/mm^3 Hemoglobin at least 10 g/dL Hepatic Not specified Renal Creatinine no greater than 1.5 mg/dL AND/OR Creatinine clearance at least 65 mL/min Calcium no greater than 11 mg/dL Cardiovascular No uncontrolled heart disease No uncontrolled hypertension Exclusion Criteria: Uncontrolled diabetes Interval between surgery and adjuvant therapy more than 3 months Sign of recurrence on CT scan or ultrasound or PET-CT No palpable subclavicular lymph nodes or involvement after cytology needle aspiration No lymph nodes greater than 1 cm on CT scan With Weight loss greater than 10% from baseline With other prior or concurrent malignancy except basal cell skin cancer or carcinoma in situ of the cervix Be pregnant

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 68 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: Surgery alone<br>No adjuvant treatment after radical resection is developed in this arm | |
| Experimental: Adjuvant Chemoradiation<br>Adjuvant chemoradiation after radical resection is developed in this arm | Radiation: Adjuvant Chemoradiation<br>* Patients receive Paclitaxel 135-150mg/m2 (D1 and D29) and Cisplatin or Nedaplatin 50-75mg/m2 (D1 and D29) every 4 weeks, concurrent with radiotherapy. Prophylactic polyethylene glycol recombinant human G-CSF is administered 48 hours after chemotherapy. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity.<br>Drug: Paclitaxel<br>* 135-150mg/m2 (D1 and D29)<br>Drug: Cisplatin or Nedaplatin<br>* 50-75mg/m2 (D1 and D29)<br>|
| Active Comparator: Adjuvant Radiation<br>Adjuvant radiation after radical resection is developed in this arm | Radiation: Adjuvant Radiation<br>* Patients undergo radiotherapy once daily 5 days a week for an average of 5.5 weeks within 12 weeks after surgery in the absence of disease progression or unacceptable toxicity.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-free survival (DFS) | From the date of randomization to the date of first failure or last follow-up | up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) | From the date of randomization to the date of death or last follow-up | up to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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StageⅡB-Ⅲ esophageal cancer, adjuvant radiotherapy, adjuvant chemoradiotherapy