Chemoradiotherapy of Capecitabine With or Without Oxaliplatin Versus Cisplatin-5-FU for Esophageal Squamous Cancer

Study Overview
=================
Brief Summary
-----------------
A three-arm Phase III trial was started in Oct. 2014. Definitive chemoradiotherapy with cisplatin plus 5-fluorouracil is the standard in Western countries in esophagus cancer. But in China because of its toxic reaction, most of patients stop the halfway. Because low toxicity, the chemotherapy regimen of capecitabine with or without oxaliplatin are widely used in clinical. The purpose of this study is to confirm the difference of Capecitabine plus with or without oxaliplatin over cisplatin plus 5-fluorouracil with definitive chemoradiotherapy for esophagus squamous cell carcinoma. A total of 249 patients will be accrued from China within 2 years. The primary endpoints are grade 3-5 AEs and overall survival and the secondary endpoints include progression-free survival, response rate, pathologic complete response rate.

Detailed Description
-----------------
We plan to recruit the patients who were pathologically confirmed with esophageal squamous cell carcinoma from the Oct 2014. The patients will be divided into three groups.Experimental group 1 : single drug Capecitabine and concurrent radiotherapy.Experimental group 2: Capecitabine plus oxaliplatin and concurrent radiotherapy. Control group:cisplatin plus 5-fluorouracil and concurrent radiotherapy. To evaluate the adverse events and the overall survival of the three group. Also observe the patient's progression-free survival, response rate, pathologic complete response rate.

Official Title
-----------------
Three-arm Phase III Trial Comparing Radiotherapy With Different Chemotherapy Regimens for Esophageal Cancer

Conditions
-----------------
Stage III Esophageal Squamous Cell Carcinoma, Stage II Esophageal Squamous Cell Carcinoma

Intervention / Treatment
-----------------
* Drug: Capecitabine(Aibin)
* Drug: Oxaliplatin(Aiheng)
* Radiation: Radiotherapy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: age 18-75years old Histologically proven squamous cell carcinoma of the esophagus the tumor was in T2-4N0-2M0 The patients have not received the surgery or chemo-radiotherapy. Hb≥80g/L, absolute neutrophil count ≥1.5×109/L, Plt≥90×109/L, ALT、AST≤2.5*N,Cr≤1.5*N. performance status score 0-2 Exclusion Criteria: pregnant, lactating women Oxaliplatin or fluorouracil Allergy or metabolic disorders Radiotherapy contraindications History of organ transplantation Brain metastasis The peripheral nervous system disorders Severe infection Oral capecitabine who have difficulty with,such as dysphagia,The activities of digestive ulcer, Gastrointestinal bleeding Severe chronic diseases, such as, hepatopathy, nephropathy, respiratory disease,high blood pressure, diabetes. Other malignant tumor in recent 5 years.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Capecitabine-oxaliplatin-radiotherapy<br>oxaliplatin：65mg/m2，d1，8，22, 29,I.V.or d1, 8, 22, 29, 43, 50, 64, 71,I.V.plus,capecitabine: 625mg/m2, bid d1-5; q1w, po,6 weeks or 12 weeks in total. radiotherapy： 50-50.4Gy ，1.8-2 Gy/d，5d/w. | Drug: Capecitabine(Aibin)<br>* capecitabine(Aibin)：625mg/m2, bid d1-5; q1w, po,5 weeks in total<br>* Other names: Aibin;Drug: Oxaliplatin(Aiheng)<br>* Oxaliplatin(Aiheng)：65mg/m2，d1，8, 22, 29,I.V.<br>* Other names: Aiheng;Radiation: Radiotherapy<br>* concurrent radiotherapy： 50Gy in total，2 Gy/d，5d/w，Until disease progression or unacceptable toxicity<br>* Other names: Radiation Therapy;|
| Active Comparator: cisplatin with 5-FU and radiotherapy<br>cisplatin: 75mg/m2 d1，29 or d1, 29, 57, 85, 5-Fu：750mg/m2 CIV24h d1-4，d29-32 or d1-4，d29-32, d57-60, d85-88. radiotherapy： 50-50.4Gy ，1.8-2 Gy/d，5d/w. | Radiation: Radiotherapy<br>* concurrent radiotherapy： 50Gy in total，2 Gy/d，5d/w，Until disease progression or unacceptable toxicity<br>* Other names: Radiation Therapy;|
| Experimental: Capecitabine and radiotherapy<br>capecitabine: 625mg/m2, bid d1-5; q1w, po,6 weeks or 12 weeks in total, radiotherapy： 50-50.4Gy ，1.8-2 Gy/d，5d/w. | Drug: Capecitabine(Aibin)<br>* capecitabine(Aibin)：625mg/m2, bid d1-5; q1w, po,5 weeks in total<br>* Other names: Aibin;Radiation: Radiotherapy<br>* concurrent radiotherapy： 50Gy in total，2 Gy/d，5d/w，Until disease progression or unacceptable toxicity<br>* Other names: Radiation Therapy;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Grade 3/5 acute toxicities | Grade 3/5 acute toxicities occurred during or within 90 days after RT | 90 days | 
| OS-2 year | Overall Survival rate in 2 year from Randomization | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS-2 year | Progression Free Survival rate in 2 year from Randomization | 2 years | 
| overall remission rate, ORR | overall remission rate after CRT | 16 weeks | 
| quality of life, Qol | quality of life evaluation | 16 weeks | 
| pathologic complete response rate | pathologic complete response rate confirmed by gastroscope biopsy | 16 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Chemoradiotherapy， Esophageal Squamous Cancer