Changes in Tumor Tissue and Serum Biomarkers Before and After Cetuximab Combined With Preoperative Radiotherapy in Locally Advanced Thoracic Esophageal Squamous Cell Carcinoma

Study Overview
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Brief Summary
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This study aim to investigate Changes in tumor tissue and serum biomarkers before and after cetuximab combined with preoperative radiotherapy in locally advanced thoracic middle-lower segment esophageal squamous cell carcinoma.We want to find one or more effective biomarkers to predict and evaluate the patients who will be benefit from cetuximab combined with preoperative radiotherapy.

Official Title
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Changes in Tumor Tissue and Serum Biomarkers Before and After Cetuximab Combined With Preoperative Radiotherapy in Locally Advanced Middle or Lower Thoracic Esophageal Squamous Cell Carcinoma

Conditions
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Locally Advanced Thoracic Middle-lower Segment Esophageal Squamous Cell Carcinoma

Intervention / Treatment
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* Radiation: preoperative radiotherapy
* Drug: cetuximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: (1)18 to 65 years old,male or female (2)Pathologically or cytologically proven thoracic middle-lower esophageal squamous cell carcinoma; (3)clinical stage II or stage III; (4)Primary tumors can be measured; (5)Karnofsky score >70; (6)Estimated life expectancy of at least 12 weeks; (7)reproductive age women should ensure that before entering the study period contraception; (8)Hemoglobin≥90.0g/dL,white blood cell count（WBC）≥ 4000 cells/mm³,Platelet count≥100,000 cells/mm³; (9)Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 times upper limit of normal,bilirubin normal; (10)Creatinine normal OR creatinine clearance ≥ 60 mL/min; (11)Patients have good compliance to treatment and follow-up of acceptance; (12)Forced expiratory volume in one second（FEV1） ≥ 1.5 litre or ≥ 75% of the reference value; (13)Considered operable (i.e. appropriate organ functions and ability to undergo general anesthesia); (14)No severe or uncontrolled cardiovascular disease; (15)No active uncontrolled infection; Exclusion Criteria: Patient who have distant metastasis The primary tumor or lymph node already received surgical treatment (except for biopsy); Patient who received radiotherapy for primary tumor or lymph node; Patient who received the the epidermal growth factor targeted therapy; Patient who received chemotherapy or immunotherapy; Patient who suffered from other malignant tumor; Epidermal growth factor receptor（EGFR）mutation（-）; Patient who have taken other drug test within 1 month; Pregnant woman or Lactating Women and Women in productive age who refuse to take contraception in observation period; Subject with a severe allergic history or idiosyncratic; Subject with severe pulmonary and cardiopathic disease history; Refuse or incapable to sign the informed consent form of participating this trial; Drug abuse or alcohol addicted; Subject with a Personality or psychiatric diseases, people with no legal; capacity or people with limited capacity for civil conduct;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>All patients in the arm receive cetuximab combined with preoperative radiotherapy at first. 4-6 weeks after the rdiaotherapy，patients receive right thoracotomy with three incisions radical surgery. | Radiation: preoperative radiotherapy<br>* Patients receive intensity modulated radiation therapy(IMRT) or image-guided radiation therapy(IGRT)from week 1 to week 4,once a day, 5 times per week. Radiotherapy dose：95% gross tumor volume（GTV-T） 40Gy/20f，GTV-N 40Gy/20f，CTV-T 40Gy/20f，CTV-N 40Gy/20f.<br>Drug: cetuximab<br>* 400mg/m2/week, 2 hours,iv,at week 1;250mg/m2/week,1hour,iv,at week 2-4<br>* Other names: C225;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Expression of Survivin protein in Esophageal Squamous Cell Carcinoma before and after Radiotherapy | Survivin, an inhibitor of apoptosis protein, is highly expressed in most cancers and associated with radiotherapy resistance, increased tumor recurrence, and shorter patient survival. | before radiotherapy and 1 months after the radiotherapy | 
| Expression of p53 in Esophageal Squamous Cell Carcinoma before and after Radiotherapy | p53 (also known as protein 53 or tumor protein 53), is a tumor suppressor protein that in humans is encoded by the TP53 gene.p53 is important in multicellular organisms and involved in preventing cancer. | before radiotherapy and 1 months after the radiotherapy | 
| changes of serum vascular endothelial growth factor（VEGF）level before and after radiotherapy | Vascular endothelial growth factor (VEGF) is a signal protein produced by cells that stimulates vasculogenesis and angiogenesis. | before radiotherapy and 1 months after the radiotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of life (QOL) | Quality of life (QOL) as measured by European Organization for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-C30） | up to 3 years | 
| Overall survival | time from randomization to death | up to 3 years | 
| PFS（progression-free survival） | time from randomization to one of the following events, whichever comes first: Tumor progression at any time (progression of primary tumor or local lymph nodes, appearance of new lesions) Recurrence at local, regional or distant site after surgery Death from any cause | up to 3 years | 
| local control rate（LCR） | Time to locoregional failure after R0 resection | up to 3 years | 
| Pathological remission |  | 1 months after the end of surgery | 
| grade 3-5 adverse events | Grade 3-5 adverse events as assessed by NCI Common Toxicity Criteria for Adverse Effects (CTCAE) v3.0，such as esophagitis、pneumonitis and hematologic toxicity | up to 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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tumor tissue and serum biomarkers, cetuximab, preoperative radiotherapy, esophageal squamous cell carcinoma