Induction Chemotherapy Followed by Cetuximab Plus Definitive Radiotherapy Versus Radiation Plus Cisplatin

Study Overview
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Brief Summary
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A phase III trial of induction chemotherapy followed by definitive radiotherapy plus Cetuximab versus chemoradiation in unresectable, locally advanced, squamous cell carcinoma of the head and neck (HNC).

Detailed Description
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The objective of this trial is to determine whether Cetuximab and radiation preceded by an induction chemotherapy, may be superior to an established chemoradiation program for HNC (RTOG regimen, Adelstein DJ J.Clin.Oncol. 2003;21:92-98).

Official Title
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Induction Chemotherapy Followed by Cetuximab Plus Definitive Radiotherapy Versus Radiation Plus Cisplatin

Conditions
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Squamous Cell Carcinoma of the Head and Neck

Intervention / Treatment
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* Drug: docetaxel - cisplatin - 5-fluorouracil
* Radiation: radiotherapy
* Drug: cetuximab
* Drug: cisplatin
* Radiation: radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: > 18 years of age Histologically or cytologically confirmed diagnosis of HNSCC Stage III/IV, not suitable for surgery (definitive cure rate improbable, technically unresectable or medical contraindication for surgery) At least one uni-dimensional measurable lesion either by CT scan or MRI Signed written informed consents prior to beginning protocol Specific procedures: Tumor tissue available for immunohistochemical staining of EGFR expression and HPV Life expectancy of > 3 months at study entry ECOG Performance Status of <2 at study entry. Effective contraception if risk of conception exists. Neutrophils > 2.0/mm³, platelet count > 100,000/mm³, and hemoglobin > 10 g/dl Normal liver function Serum creatinine > 1.25 x ULN and/or creatinine clearance > 60 ml/min Exclusion Criteria: Prior systemic chemotherapy and/or radiotherapy Known peripheral neuropathy > grade 2 NCI-CTC version 3.0 Known chronic heart failure Prior surgery, excluding prior diagnostic biopsy Known drug abuse Active uncontrolled infection Other concomitant anticancer therapy Distant metastasis Concurrent chronic systemic immune therapy, chemotherapy for disease other than cancer, or hormone therapy not indicated in the study protocol Clinically relevant coronary artery disease or history of a myocardial infarction within the last 12 months before study entry Medical or psychological condition that would not permit the patient to complete the trial or sign informed consent Nasopharyngeal carcinoma WHO type II or III Known allergic reaction against any of the components of the treatment Pregnancy (absence confirmed by beta-HCG test) or lactation period Any prior or on-going investigational medication Previous or current malignancy except basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ARM A<br>Induction chemotherapy: TCF (Vermorken, N Eng J Med 2007) Definitive treatment: RT + C-mab (Bonner, N Eng J Med 2006) | Drug: docetaxel - cisplatin - 5-fluorouracil<br>* docetaxel 75 mg/sqm day1 cisplatin 75 mg/sqm day1 5-fluorouracil 750 mg/sqm/d c.i. day1 to day4 q21<br>Radiation: radiotherapy<br>* Conformal radiotherapy or IMRT should be employed. Standard radiotherapy: Minimum radiation dose 70 Gy. Additional boost up to 10 Gy if clinically indicated.<br>Drug: cetuximab<br>* 400 mg/sqm at the 1st infusion - before starting RT 250 mg/sqm weekly - concurrent with RT up to the last week of treatment<br>|
| Active Comparator: ARM B<br>RT + Cddp (RTOG, Adelstein, J Clin Oncol 2003) | Drug: cisplatin<br>* Cisplatin, 100 mg/sqm every 3 weeks, three times, concurrent with RT, starting from day 1 of treatment.<br>Radiation: radiotherapy<br>* Conformal radiotherapy or IMRT should be employed. Standard radiotherapy: Minimum radiation dose 70 Gy. Additional boost up to 10 Gy if clinically indicated.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of acute and late toxicities in the two arms |  | 5 years | 
| Progression free survival |  | 5 years | 
| Locoregional control |  | 5 years | 
| Response rate |  | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Locally advanced HNSCC, Chemo-radiation, Induction chemotherapy, Stage III/IV, Unresectable disease