Paclitaxel, Cisplatin,5-FU vs. Radiotherapy Plus Paclitaxel, Cisplatin as Preoperative Therapy for Locally Advanced ESC

Study Overview
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Brief Summary
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This is a Phase III clinical trail which Comparing Paclitaxel, Cisplatin Plus 5-FU (TCF) Versus Radiotherapy with Paclitaxel Plus Cisplatin (TC-RT) as Preoperative Therapy for Locally Advanced Esophageal Squamous Cancer. The Preoperative chemoradiotherapy with radical surgery is the standard treatment in China. But, many patients do not receive this treatment for many other reasons. Most of them refused or abandon radiotherapy because of the Intolerable adverse effects of radiotherapy, so we have launched a randomized controlled trial to confirm the non-inferiority of TCF over chemoradiotherapy with TC (TC-RT) as preoperative therapy for locally advanced esophageal squamous cancer in overall survival.

Official Title
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A Phase III Trial Comparing Paclitaxel, Cisplatin Plus 5-FU (TCF) Versus Radiotherapy With Paclitaxel Plus Cisplatin (TC-RT) as Preoperative Therapy for Locally Advanced Esophageal Squamous Cancer

Conditions
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Esophageal Cancer Stage IIB, Esophageal Cancer Stage III

Intervention / Treatment
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* Combination Product: Paclitaxel, Cisplatin Plus 5-FU (TCF)
* Radiation: radiochemotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically proven squamous cell carcinoma. All lesions are located in the thoracic esophagus. Clinical stages IIB and III (excluding T4) based on the 7th UICC-TNM classification. 20-75 years old. ECOG performance status of 0 or 1. Measurable lesions not required. No prior therapy against esophageal cancer except for complete resection by endoscopic mucosal resection/endoscopic submucosal dissection with either pM1/M2 disease or pM3 disease without vascular infiltration. No prior chemotherapy, radiotherapy or hormonal therapy against any cancers Adequate organ function. Written informed consent. Exclusion Criteria: Synchronous or metachronous double cancers, except for intramucosal tumor curatively resected by local therapy. Active infection requiring systemic therapy Positive hepatitis B surface antigen and hepatitis B core antigen or human immunodeficiency virus antibody.(only positive hepatitis B surface antigen should receive anti-virus treatment during study) Pregnant or lactating women or women of childbearing potential. Patients requiring systemic steroid medication. Iodine hypersensitivity. Psychiatric disease. Hypersensitivity for CremophorEL. Poorly controlled diabetes. Severe emphysema or pulmonary fibrosis. Poorly controlled hypertension. Unstable angina within 3 weeks or with a history of myocardial infarction within 6 months.

Ages Eligible for Study
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Minimum Age: 20 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Paclitaxel, Cisplatin Plus 5-FU (TCF)<br>preoperative chemotherapy with three cycles of TCF(Paclitaxel 135mg/m2 D1;Cisplatin 60mg/m2 D1 or 20mg/m2 D1-D3;5-fluorouracil 600mg/m2 D1-D5；repeated every 3 weeks | Combination Product: Paclitaxel, Cisplatin Plus 5-FU (TCF)<br>* preoperative chemotherapy with three cycles of TCF(Paclitaxel 135mg/m2 D1;Cisplatin 60mg/m2 D1 or 20mg/m2 D1-D3;5-fluorouracil 600mg/m2 D1-D5；repeated every 3 weeks)<br>|
| Experimental: Preoperative radiochemotherapy<br>preoperative radiochemotherapy (41.4 Gy/23 fractions or 40 Gy/20 fractions) with four cycles of TP(Paclitaxel 45mg/m2 on D1 and Cisplatin 20mg/m2 D1,repeated every week | Radiation: radiochemotherapy<br>* preoperative radiochemotherapy (41.4 Gy/23 fractions or 40 Gy/20 fractions) with four cycles of TP(Paclitaxel 45mg/m2 on D1 and Cisplatin 20mg/m2 D1,repeated every week)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival |  | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Free Survival |  | 3years | 
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | All participants with treatment-related adverse events as assessed by CTCAE v4.0 | through study completion, an average of 1 year | 
| Objective Response Rate |  | up to 24 weeks | 
| Rate of R0 resection |  | up to 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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preoperative chemotherapy, preoperative chemoradiotherapy, clinical trial, phase III, Esophageal squamous cancer