Induction and Concurrent Chemoradiotherapy With Cetuximab for Patients With Locally Advanced Nasopharyngeal Carcinoma

Study Overview
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Brief Summary
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Standard of care for treatment of nasopharyngeal carcinoma is chemoradiation with concurrent cisplatin. Addition of a second agent, cetuximab, which targets nasopharyngeal carcinoma cells with high EGFR protein expression, may enhance the effectiveness of radiation and result in better tumour control. This study investigates the addition of 2 cycles of cisplatin/5FU chemotherapy with cetuximab, followed by cisplatin and cetuximab concurrent with radiation, for treatment of locally advanced nasopharyngeal carcinoma.

Official Title
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Induction and Concurrent Chemoradiotherapy With Cetuximab for Patients With Locally Advanced Nasopharyngeal Carcinoma

Conditions
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Nasopharyngeal Carcinoma

Intervention / Treatment
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* Drug: Cetuximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed written informed consent Inpatients or outpatients, 18-65 years of age Histologically confirmed, newly diagnosed locally advanced (UICC/AJCC stage III to IVB) nasopharyngeal carcinoma requiring radiotherapy Evidence of unidimensional measurable disease as per RECIST criteria No systemic metastatic disease (M0) ECOG performance status of 0 or 1 at study entry Effective contraception White blood cell count ≥ 3,000/mm3 with neutrophils ≥1,500/mm3, platelet count ≥100,000/mm3, hemoglobin ≥ 5.6 mmol/L (9 g/dL) Total bilirubin ≤ 1.5x upper reference range AST & ALT ≤ 1.5x upper reference range Glomerular filtration rate > 60 ml/min Serum creatinine ≤ 1.25x upper reference range Exclusion Criteria: Previous radiotherapy, chemotherapy, surgery (excluding diagnostic biopsy) or any investigational drug for the NPC Concurrent chronic systemic immune therapy, targeted therapy, anti-VEGF therapy or EGFR-pathway targeting therapy not indicated in this study protocol Known hypersensitivity reaction to any of the components of study treatments Pregnancy or lactation period Systemic metastatic disease Clinically relevant coronary artery disease, history of myocardial infarction in the last 12 months, or high risk of uncontrolled arrhythmia Peripheral neuropathy > grade 1 Previous malignancy except basal cell cancer of the skin or preinvasive cancer of the cervix Known alcohol or drug abuse Medical or psychological conditions that would not permit the patient to complete the study or sign informed consent Legal incapacity or limited legal capacity

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: Cetuximab and chemotherapy<br>2 cycles of neoadjuvant cisplatin and 5FU (3 weekly), given with weekly cetuximab, followed by 7 doses of weekly cisplatin and cetuximab concurrent with radiotherapy | Drug: Cetuximab<br>* Cetuximab loading dose of 400mg/m2, then weekly dose of 250mg/m2 for 12 doses; Neoadjuvant Cisplatin 75mg/m2 D1, 5FU 1000mg/m2 D2-5, for 2 cycles; Concurrent Cisplatin 30mg/m2 given with radiation 70Gy/35fraction/7weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events as a measure of safety and tolerability |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate | Assess the response rate of this combination treatment, as measured by imaging and endoscopy findings | 1 year | 
| Progression and overall survival | To assess the PFS and OS at one year | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Locally advanced nasopharyngeal carcinoma, Neoadjuvant chemotherapy, Chemoradiation, Cetuximab