A Phase II Study of Chemoradiotherapy With Nimotuzumab in Unresectable Esophageal Cancer

Study Overview
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Brief Summary
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This phase II clinical study is designed to evaluate the 1 year local tumor control rates after the targeted therapy of intensity-modulated radiation therapy synchronized chemotherapy with nimotuzumab combined with S-1 in local advanced esophageal squamous cell carcinomas based on Nutritional Risk Screening NRS2002.

Official Title
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A Phase II Study of Chemoradiotherapy With Nimotuzumab in Unresectable Esophageal Squamous Cell Carcinoma Based on Nutritional Risk Screening Score (NRS2002)

Conditions
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Esophageal Cancer, Chemoradiotherapy, Nimotuzumab, Unresectable Malignant Neoplasm

Intervention / Treatment
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* Radiation: Radiotherapy
* Drug: Nimotuzumab
* Drug: S-1


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥18 years Pathologically or cytologically proven esophageal squamous cell carcinomas in patients staged as T2-4N0-1M0-1b (AJCC 6th TNM staging, M1b limited to clavicular or celiac lymph node metastasis) Primary treatment accepted in Chinese Academy of Medical Sciences KPS ≥70 NRS score ≥2 Cervical or thoracic esophageal cancer histologically proved esophageal cell carcinoma Normal organ and marrow function as defined below: Hemoglobin: greater than or equal to 100g/L ;Leukocytes: greater than or equal to 3,500 G/L; Neutrophil: greater than or equal to 1,500 G/L; Platelets: greater than or equal to 100,000/mm3 ; Creatinine within normal upper limits; BUN within normal upper limits; AST/ALT: less than or equal to 1.5 times the upper limit; Total bilirubin: less than or equal to 1.5 times the upper limit; Alkaline phosphatase :less than or equal to 1.5 times the upper limit Informed consent Exclusion Criteria: Patients with other cancer history in 5 years except cervical carcinoma in situ and non-malignant melanoma skin cancer Any prior chemotherapy or other cancer treatment prior to this protocol With any distant metastasis in liver, lung, bone, CNS or peritoneal transplantation History of allergic reactions attributed to contrast medium, similar chemical or biologic complex Existing esophageal fistula, perforation and cachexia Existing active infection such as active tuberculosis and hepatitis Uncontrolled illness including, but not limited to, active infection, symptomatic heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness History of myocardial infarction within the past 6 months or history of ventricular arrhythmia Participation in other clinical trials currently or within 4 weeks of selection Pregnant or lactating females

Ages Eligible for Study
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Minimum Age: 18 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: Neoadjuvant Chemoradiotherapy（NCRT）<br>NCRT arm receives intensity-modulated radiotherapy concurrently with S-1（40-60/m2/d，orally twice a day） and nimotuzumab（400mg/d，by intravenous infusion once a week）. | Radiation: Radiotherapy<br>* 44.94Gy and 37.8Gy in 21 fractions to PGTV and PTV for neoadjuvant treatment. 59.92Gy and 50.4Gy in 28 fractions to PGTV and PTV for definitive treatment.<br>Drug: Nimotuzumab<br>* 400mg, by intravenous infusion once a week in 4-6 weeks.<br>Drug: S-1<br>* 40-60mg/m2/d，orally twice a day concurrently with radiotherapy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local control rate |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with acute toxicities | Acute toxicities are evaluated by NCI-CTC version 5.0 | 2-3 months | 
| R0 resection rate | The surgical procedure was radical esophagectomy after neoadjuvant therapy. | 2-3 months | 
| Pathological response rate | Pathological response were classified into five grades according to Mandard Tumor Regression Grade. | 2-3 months | 
| Tumor Response rate |  | 2-3 months | 
| Incidence of perioperative complications | During hospital stay and within the first 30 days after completion of surgery. | 2-3 months | 
| Overall survival |  | 1 year, 2 year | 
| Progression free survival |  | 1 year, 2 year | 
| Texture analysis of CT and/or MRI simulation in predicting tumor response rate and prognosis |  | 1 year, 2 year | 
| ctDNA in predicting tumor response rate and prognosis |  | 1 year, 2 year |