Nimotuzumab in Combination With Chemoradiation for Local Advanced Esophageal Squamous Cell Carcinoma

Study Overview
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Brief Summary
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Nimotuzumab is a humanized monoclonal antibody against epidermal growth factor receptor (EGFR). Clinical trials are ongoing globally to evaluate Nimotuzumab in different indications. Nimotuzumab has been approved to treat squamous cell carcinoma of head and neck (SCCHN), glioma and nasopharyngeal carcinoma in different countries. The clinical phase I study of the combination of Nimotuzumab administered concurrently with chemo-irradiation in patients with local advanced esophageal squamous cell carcinoma (LAFSCC) has shown the safety and the potential efficacy of Nimotuzumab. The concurrent trial is a clinical phase II trial designed to assess the efficacy of the combination of Nimotuzumab administered concurrently with chemo-radiotherapy in patients with LAFSCC, and to further investigate its side-effect and toxicity.

Detailed Description
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The concurrent trial is a clinical phase II trial designed to assess the efficacy of the combination of Nimotuzumab administered concurrently with chemo-radiotherapy in patients with LAFSCC, and to further investigate its side-effect and toxicity.

Official Title
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A Clinical Study of Nimotuzumab in Combination With Concurrent Chemotherapy and Radiation for Patients With Local Advanced Esophageal Squamous Cell Carcinoma

Conditions
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Squamous Cell Carcinoma

Intervention / Treatment
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* Drug: Nimotuzumab
* Drug: Placebo
* Drug: cisplatin
* Radiation: Radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Joined the study voluntarily and signed informed consent form; Age 18-75 Both genders Esophageal squamous cell carcinoma confirmed by pathology Local advanced esophageal squamous cell carcinoma (T2N0M0-TxNxM1a, AJCC 2002) No radiotherapy, chemotherapy or other treatments prior to enrollment PS ECOG 0-2 Life expectancy of more than 3 months Target lesions measurable Hemoglobin（Hb）≥9 g/dL WBC≥3x109/L, Neutrophils (ANC )≥1.5x109/L platelet count (Pt) ≥100x 109/L Hepatic function: ALAT and ASAT < 2.5 x ULN, TBIL<1.5 x ULN Renal function: creatinine < 1.5 x ULN No immuno-deficiency Use of an effective contraceptive for adults to prevent pregnancy. Exclusion Criteria: Complete esophageal obstruction Deep esophageal ulcer Esophageal perforation Haematemesis After surgery, exploratory thoracotomy, radiotherapy, chemotherapy, or targeting therapy Esophageal stent or tracheal stent placed Other malignant tumors, except for skin basal cell carcinoma, or cervical carcinoma in situ, who survived with no evidence disease for over 3 years Participation in other interventional clinical trials within 30 days Pregnant or breast-feeding women or people during the birth-period who refused to take contraceptives Drug addiction Alcoholism or AIDS Uncontrolled seizures or psychiatric diseases, loss of control over their own behavior History of serious allergic or allergy Patients who are not suitable to participate in the trial according to researchers.

Ages Eligible for Study
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Minimum Age: 18 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nimotuzumab plus chemo-irradiation<br>Nimotuzumab，chemotherapy(cisplatin )，radiotherapy | Drug: Nimotuzumab<br>* 200mg (4 bottles), once a week for 7 weeks during irradiation (week 1, week 2, week 3, week 4, week 5, week 6 and week 7). After irradiation 200mg (4 bottles), once every 4 weeks for 2 cycles (week 9 and week 13)<br>Drug: cisplatin<br>* cisplatin 25 mg/m2/d, d1-3, once every 4 weeks for 4 cycles (week 1, week 5, week 9 and week 13); 5-FU 600 mg/m2/d, d1-3, continuously infusion for 72 hrs,once every 4 weeks for 4 cycles (week 1, week 5, week 9 and week 13).<br>Radiation: Radiotherapy<br>* A total dose of 61.2 Gy will be delivered in 34 fractions at 1.8 Gy/fraction, 5 fractions per week in 6.8 weeks. Placebo: 4 bottles placebo, once a week for 7 weeks during irradiation (week 1, week 2, week 3, week 4, week 5, week 6 and week 7). After irradiation 200mg (4 bottles), once every 4 weeks for 2 cycles (week 9 and week 13)<br>|
| Placebo Comparator: Placebo plus chemo-irradiation<br>Placebo，chemotherapy(cisplatin)，radiotherapy | Drug: Placebo<br>* 4 bottles placebo, once a week for 7 weeks during irradiation (week 1, week 2, week 3, week 4, week 5, week 6 and week 7). After irradiation 200mg (4 bottles), once every 4 weeks for 2 cycles (week 9 and week 13)<br>* Other names: Nimotuzumab, Placebo;Drug: cisplatin<br>* cisplatin 25 mg/m2/d, d1-3, once every 4 weeks for 4 cycles (week 1, week 5, week 9 and week 13); 5-FU 600 mg/m2/d, d1-3, continuously infusion for 72 hrs,once every 4 weeks for 4 cycles (week 1, week 5, week 9 and week 13).<br>Radiation: Radiotherapy<br>* A total dose of 61.2 Gy will be delivered in 34 fractions at 1.8 Gy/fraction, 5 fractions per week in 6.8 weeks. Placebo: 4 bottles placebo, once a week for 7 weeks during irradiation (week 1, week 2, week 3, week 4, week 5, week 6 and week 7). After irradiation 200mg (4 bottles), once every 4 weeks for 2 cycles (week 9 and week 13)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate of Nimotuzumab combined with chemo-irradiation |  | 2 months after radiotherapy | 
| 1-yr overall survivals |  | 1 year | 
| 2-yr overall survival |  | 2 year | 
| 3-yr overall survival |  | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local progression-free survival |  | 3 years | 
| Disease progression-free survival |  | 3 years | 
| Distant metastasis rate |  | 3 years | 
| Number and grade of Participants with Adverse Events |  | 6 months | 
| Quality of life |  | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nimotuzumab, local advanced esophageal squamous cell carcinoma, chemo-irradiation