The Role of Different Cycles of Chemotherapy（Capecitabine-oxaliplatin） in Esophageal Chemoradiotherapy

Study Overview
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Brief Summary
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A two-arm (two cycles' versus four cycles' capecitabine combined oxaliplatin concurrent radiotherapy) randomised Phase III clinical trial was started in Oct. 2015. Definitive chemoradiotherapy is the standard regimen in Western countries for patients with esophageal cancer who can't receive surgery or reject surgery. But in China because of its severer toxic reaction, most of patients had to discontinue treatment at the halfway way. Thus, the chemotherapy regimen of capecitabine combined oxaliplatin are widely used in clinical due to its characristic of low toxic reaction. The purpose of this study is to confirm the efficacy and safety of the different cycles(two cycles and four cycles ) of Capecitabine-oxaliplatin in Chinese esophageal squamous carcinoma radical concurrent chemoradiotherapy. A total of 60 patients will be accrued from China within 2 years. The primary endpoint is overall survival and the secondary endpoints include progression-free survival, response rate, pathologic complete response rate and adverse events.

Detailed Description
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First: The investigators use excel generate a 5 digits random number table. After subjects sign the informed consent, investigators will chose one for themm. Subject who get an odd number will receive 2cycles' chemotheapy concurrent radiotherapy and even number receive 4cycles'. Investigators should record the congruent relationship of subjects with group code. Second: The investigators are required to record subjects' base measurements. The base measurements items:1.Tumor confirmed date,TNM staging,History of esophageal cancer treatment;2.Demographic data,past medical history;3.physical examination(a detailed system check including general neurological examination);4.vital signs,Height,Weight;5.PS score,Quality of life;6.serum biochemistry(ALT,AST,AKP,TBIL,blood glucose,BUN,Ccr,electrolyte,et al.);7. Blood RT(RBC,HGB,WBC,ANC,PLT,et al.);8.Urine routines;9.Endoscopic biopsy(More than 3 pieces of biopsy specimens),chest CT,abdomen ultrasound/CT/MRI,PET-CT,et al.;10.Blood/urine pregnancy tests;11.Collect blood samples(5 ml);12.Preserve CorpseSample. note:Check the time limit-2 weeks before get into groups. Third:Observation items during treatment include 3-8 items of the base measurements;Radiotherapy 20 times, should review of esophageal barium meal or chest CT. The investigators need to observe adverse event during treatment and eveluate the relationship of adverse event with researched therapeutic regimen according to the Common Terminology Criteria for Adverse Events,CTCAE) (V4.0, 2009-05-28) and accurately fill in Case Report Form(CRF). Fourth: Follow-up items include 3-9 items of the base measurements;bood and tissue sample should also be preserved when subject receives 16th weeks' review. The patient who withdrew from the study during researched treatment must accept the end evaluation research. The investigators must record the reason and the date of termination in patient' progress note and CRF. Cases of complete report should transfer to data administrators after investigates by clinical research associate. Data administrators input and management data.

Official Title
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Two Cycles Versus Four Cycles of Capecitabine Combined Oxaliplatin Concurrent Radiotherapy as First-line Therapy for Chinese Locally Advanced Esophageal Squamous Cell Carcinomas, an Open Randomised Phase III Cilinical Trial

Conditions
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Stage III Esophageal Squamous Cell Carcinoma, Esophageal Neoplasms

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Voluntary participation and signed a consent form Histologically proven squamous cell carcinoma of the esophagus, initial treatment (Not had surgery, radiotherapy, chemotherapy or targeted therapy) the tumor was in T2-4N0-2M0, locally advanced（AJCC2002） Have a measurable lesions. Male or female who has fertility is willing to take contraceptive measures in the experiment WBC≥3x10 9/L；Hb≥80g/L；ANC ≥1.5x10 9/L；PLT ≥100x10 9/L；TBIL< 1.5xN；AST (SGOT)/ALT (SGPT) ≤2.5xN；Cr≤1.5xN. Performance status score 0-2 Expected lifetime>3 months Exclusion Criteria: Pregnant, lactating women or With fertility but did not use contraceptive measures Has a history of severe allergic or idiosyncrasy Hab been treated with surgery, radiation and chemotherapy or targeted therapy for esophageal cancer After exploratory thoracotomy or Laying an esophageal tracheal stent Received a major surgery treatment within 28 days prior to the start of research and treatment History of organ transplantation Has uncontrolled seizures or Lose self-knowledge because of mental illness Severe infection Oral capecitabine who have difficulty with,such as esophageal obstructed completely, 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
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Minimum Age: 45 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: Capecitabine-oxaliplatin 2 cycles<br>oxaliplatin：65mg/m2,d1,8,22,29,I.V; capecitabine: 625mg/m2, bid d1-5; q1w, po,5 weeks in total; radiotherapy:50Gy,2 Gy/d,5d/w. | Drug: Capecitabine(Aibin)<br>* capecitabine(Aibin):625mg/m2,bid d1-5; q1w, po,5 or 10 weeks in total<br>* Other names: Aibin;Drug: Oxaliplatin(Aiheng)<br>* Oxaliplatin(Aiheng):65mg/m2,d1,8,22,29,I.V. or Oxaliplatin(Aiheng):65mg/m2,d1,8,22,29,43,50,64,71,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: Capecitabine-oxaliplatin 4 cycles<br>oxaliplatin:65mg/m2,d1,8,22, 29,43,50,64,71,I.V; capecitabine:625mg/m2,bid d1-5; q1w, po,10 weeks in total; radiotherapy:50Gy ,2 Gy/d,5d/w. | Drug: Capecitabine(Aibin)<br>* capecitabine(Aibin):625mg/m2,bid d1-5; q1w, po,5 or 10 weeks in total<br>* Other names: Aibin;Drug: Oxaliplatin(Aiheng)<br>* Oxaliplatin(Aiheng):65mg/m2,d1,8,22,29,I.V. or Oxaliplatin(Aiheng):65mg/m2,d1,8,22,29,43,50,64,71,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;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival, OS |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progression-free survival,PFS |  | 2 years | 
| overall remission rate, ORR |  | 16 weeks | 
| serious adverse event，SAE |  | 16 weeks | 
| quality of life, Qol |  | 16 weeks | 
| pathologic complete response rate |  | 16 weeks | 
| disease control rate,DCR |  | 16 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chemoradiotherapy, Esophageal Squamous Cancer, Capecitabine and oxaliplatin, Chinese, Randomized Controlled Trials