Nimotuzumab in Combination With Chemoradiation for Nasopharyngeal Cancer

Study Overview
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Brief Summary
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Nimotuzumab is an IgG1 humanized monoclonal antibody that recognized an epitope located in the extra cellular domain of the human epidermal growth factor receptor (EGFR). Clinical trials are ongoing globally to evaluate nimotuzumab in different indications. Nimotuzumab has been granted approval for use in squamous cell carcinoma of head and neck (SCCHN), glioma and nasopharyngeal cancer in different countries. The Clinical efficacy has been shown in adult with head and neck cancer. The study assessed the clinical efficacy, and safety of the combination of Nimotuzumab administered concomitantly with chemotherapy and radiotherapy in patients with advanced nasopharyngeal cancer.

Detailed Description
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Patients with advanced nasopharyngeal cancer will be randomized to 2 arms. The patients in experimental arm will be treated with Nimotuzumab which will be used concurrently with radiotherapy and chemotherapy. The chemotherapy regimen were Cisplatin monotherapy. The active comparator arm will be administered chemotherapy and radiotherapy only. The dose and regimen were the same with experiment arm. The patients'hematopoietic , hepatic and renal function tests will be monitored weekly, a physical exam and reassessment of the tumor will be performed at the first and the fourth month, and followup every six months to evaluate the survival index in three years after the study.

Official Title
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A Prospective,Randomized,Double-Blind,Controlled,Multicenter,Phase III Study of Nimotuzumab in Combination With Chemotherapy and Radiotherapy for Patients With Local Advanced Nasopharyngeal Cancer

Conditions
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Nasopharyngeal Cancer

Intervention / Treatment
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* Drug: Nimotuzumab
* Drug: placebo plus chemoradiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Joined the study voluntary and signed informed consent form Age 18-70，both genders. Nasopharyngeal cancer was confirmed by pathology. Nasopharyngeal cancer 2008 Stages: Ⅲ/Ⅳa. Primary lesions can measurable. Karnofsky Performance Scale >70. Life expectancy of more than 6 months. Use of an effective contraceptive method for women when there is a risk of pregnancy during the study. Haemoglobin≥100g/L ,WBC ≥4×109/L, platelet count≥100×109/L Hepatic function:ALAT、ASAT< 1.5 x ULN, TBIL< 1.5 x ULN Renal function: Creatinine < 1.5 x ULN Exclusion Criteria: Evidence of distant metastasis Primary lesions or lymph node have been operated (except of operation for biopsy) Previous radiotherapy Received other anti EGFR monoclonal antibody treatment Previous chemotherapy or immunization therapy Other malignant tumor (except of Non-melanoma Skin Cancer or carcinoma in situ of cervix) Participation in other interventional clinical trials within 1 month Peripheral neuropathy is more than I stage Pregnant or breast-feeding women and women who refused to take contraceptive method History of serious allergic or allergy History of Serious lung or heart disease Refused or can't signed informed consent form Drug abuse or alcohol addiction Personality or psychiatric disease, and persons without capacity for civil conduct or persons with limited capacity for civil conduct

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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 chemoradiotherapy<br> | Drug: Nimotuzumab<br>* Nimotuzumab:(200mg/w,weekly, 7-8 weeks, one week before radiotherapy) Radiotherapy: IMRT: Nasopharynx: GTV 66-78. 2Gy,CTV1 60-64Gy,CTV2 54-60Gy.30-34 times, 2.20-2.30Gy/time,once a day, 5 days/w, 6-7 weeks. Neck: lymph node positive, GTVn 60-70Gy, once a day, 5 days/w, 6-7weeks; lymph node negative, CTVn50-55Gy, once a day, 5 days/w, 6-7 weeks. CRT: Nasopharynx, 70-(76-80)Gy, 35-(38-40)times, 2Gy/time, once a day, 5 days/w, 6-8weeks. If disease residual when radiotherapy finished could increase the dose appropriate. Neck: lymph node positive, 64-70 Gy, 32-35 times, 2 Gy/time, once a day, 5 days/w, 6-7 weeks; lymph node negative, 50-56 Gy, 25-28 times,2 Gy/time, once a day, 5 days/w, 5-6weeks cisplatin Chemotherapy: Cisplatin (100 mg/m2,1 time/21d, 3 times，on days 2, 23, 44 during the radiotherapy)<br>|
| Placebo Comparator: placebo plus chemoradiotherapy<br> | Drug: placebo plus chemoradiotherapy<br>* Placebo treatment:4 bottles/w,weekly, 7-8 weeks, one week before radiotherapy Radiotherapy: IMRT: Nasopharynx: GTV 66-78. 2Gy,CTV1 60-64Gy,CTV2 54-60Gy.30-34 times, 2.20-2.30Gy/time,once a day, 5 days/w, 6-7 weeks. Neck: lymph node positive, GTVn 60-70Gy, once a day, 5 days/w, 6-7weeks; lymph node negative, CTVn50-55Gy, once a day, 5 days/w, 6-7 weeks. CRT: Nasopharynx, 70-(76-80)Gy, 35-(38-40)times, 2Gy/time, once a day, 5 days/w, 6-8weeks. If disease residual when radiotherapy finished could increase the dose appropriate. Neck: lymph node positive, 64-70 Gy, 32-35 times, 2 Gy/time, once a day, 5 days/w, 6-7 weeks; lymph node negative, 50-56 Gy, 25-28 times,2 Gy/time, once a day, 5 days/w, 5-6weeks cisplatin Chemotherapy: Cisplatin (100 mg/m2,1 time/21d, 3 times，on days 2, 23, 44 during the radiotherapy)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the local-regional control rates of the disease in the advanced nasopharyngeal cancer patients subject to the treatment with Nimotuzumab in combination with chemoradiation |  | 3 months after the Nimotuzumab treatment finished | 
| To determine the safety of the treatment with Nimotuzumab in combination with chemoradiation |  | within study period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the Disease-free survival、Tumor control probability、Distant recurrence rate in the patients subject to the treatment at years 1,2,3 |  | 3 year | 
| To determine the Progression free suivival、Diease free survival、Overall survival in the patients subject to the treatment |  | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nimotuzumab, Nasopharyngeal cancer, chemoradiation