Study to Evaluate Induction Chemotherapy Using Docetaxel, Cisplatin and Fluorouracil in Concurrence With Intensity-modulated Radiotherapy for Local Recurrent Nasopharyngeal Carcinoma (NPC)

Study Overview
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Brief Summary
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Study Objective: Primary 1. To evaluate the complete response (CR) rate with induction chemotherapy using Docetaxel, Cisplatin and Fluorouracil(TPF) followed by Docetaxel plus Cetuximab (TC) in concurrence with intensity-modulated radiotherapy (IMRT). Secondary To determine the overall response rate. To determine the locoregional and distant control rate To determine the progression-free survival (PFS) To determine the overall survival (OS) To determine the safety of the induction chemotherapy and concurrent chemoradiation plus Cetuximab.

Official Title
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Phase II Study to Evaluate Induction Chemotherapy Using Docetaxel, Cisplatin and Fluorouracil Followed by Weekly Docetaxel and Cetuximab in Concurrence With Intensity-modulated Radiotherapy for Locally Recurrent Nasopharyngeal Carcinoma (NPC)

Conditions
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Nasopharyngeal Carcinoma

Intervention / Treatment
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* Drug: Docetaxel, Cisplatin, 5-FU and Cetuximab


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Recurrent T3N0-N1M0 NPC (by AJCC/UICC 6th edition) and at least 1 year from the end of last primary course of radiotherapy Age > 18 to < 70 years Performance status: < 1 by ECOG System (Appendix I) Adequate bone marrow & renal function Patients having Bilirubin =< 1.5 x ULN, ASAT & ALST=< 1.5 x ULN, Serum creatinine=< 1.25 x ULN and / or Creatinine clearance >= 60ml/min Patients having WBC >= 3x10e9/L, Neutrophils 1.8x10e9/L, Platelets >= 100 x10e9/L,Hemoglobin >=10g/dL Signed written informed consent Patients must have at least one measurable lesion Exclusion Criteria: Use of investigational agent within the past 28 days Pre-treatment with an anti-EGFR drug Severe cardiac disease such as heart failure, coronary artery disease or myocardial infarction within the last 12 months History of severe pulmonary diseases Active infection or other systemic disease under poor control Uncontrolled chronic neuropathy Know grade 3 or 4 allergic reaction to any of the components of the treatment Estimated life expectancy is less than 3 months Pregnancy or breast feeding

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental 1<br>Induction chemotherapy using Docetaxel, Cisplatin and 5-FU for week 1 to week 9 and followed by concurrent chemoradiation plus cetuximab from week 10 to week 16 | Drug: Docetaxel, Cisplatin, 5-FU and Cetuximab<br>* Induction phase (Weeks 1-9): Drug Docetaxel Docetaxel 75 mg/m2 IV, D1 every 3 weeks for 3 cycles Drug Cisplatin Cisplatin 75 mg/m2 IV, D1 every 3 weeks for 3 cycles Drug Fluorouracil Fluorouracil 750 mg/m2 IV, D1-4 every 3 weeks for 3 cycles Concurrent phase (weeks 10-16): Drug Docetaxel Docetaxel 15 mg/m2 IV, D1 weekly for 7 weeks (Weeks 10-16) Drug Cetuximab Cetuximab 400 mg m2 IV, D1 initial dose, then 250 mg/m2 weekly for 7 week (Weeks 10-16) IMRT (60 Gy to GTV or biological dose equivalent): 2 Gy/fraction/day, D1-5 per week, for 6 weeks (Weeks 11-16)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete response rate | Complete response rate is defined as the proportion of subjects with disappearance of all target lesions after induction and concurrent therapies. | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate | Defined as the proportion of subjects with best response (confirmed CR or PR) compared to the overall treated group. | 5 years | 
| Locoregional and distant control rate | Defined as the proportion of subjects with no local or nodal progression or recurrence and no distant disease progression or recurrence compared to the overall treated group. | 5 years | 
| Progression free survival | Defined as the time in months from first dose of cetuximab until PD is observed or death occurs due to any cause within 90 days after the last tumour assessment or first cetuximab dose. | 5 years | 
| Overall survival | Defined as the time in months from first dose of cetuximab to the date of death is observed. If subject has not died, the survival time will be censored on the last date the subject was known to be alive. | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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induction chemotherapy, docetaxel, cisplatin, fluorouracil, cetuximab, intensity-modulated radiotherapy