Induction Chemotherapy With TP+5-FU or TP+Cetuximab Followed by Radioimmuptherapy for Locally Advanced or Not Resectable SCCHNN

Study Overview
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Brief Summary
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This multicentre, randomised Phase II Pilot Study evaluates the efficacy of docetaxel, cisplatin and 5-fluorouracil or Cetuximab, followed by Cetuximab with radiotherapy.

Detailed Description
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It will be evaluated whether 5-FU can be replaced by immunotherapy with cetuximab within a taxane/cisplatin-containing induction-chemotherapy scheme for advanced carcinoma of the head and neck. As 5-FU causes severe mucosal toxicities which are added to known toxicities of cisplatin, a combination-therapy with reduced toxicities and same efficacy would be a acceptable alternative to patients.

Official Title
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Randomised Phase II Pilot Study: Induction Chemotherapy With Docetaxel, Cisplatin and Cetuximab Versus Docetaxel, Cisplatin and 5 FU Followed by Radiotherapy With Cetuximab for Locally Advanced or Not Resectable Carcinoma of the Head and Neck

Conditions
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Squamous Cell Carcinoma of the Hypopharynx Stage III, Squamous Cell Carcinoma of the Hypopharynx Stage IV, Squamous Cell Carcinoma of the Larynx Stage III, Squamous Cell Carcinoma of the Larynx Stage IV, Squamous Cell Carcinoma of the Oropharynx Stage III, Squamous Cell Carcinoma of the Oropharynx Stage IV, Squamous Cell Carcinoma of the Oral Cavity Stage III, Squamous Cell Carcinoma of the Oral Cavity Stage IV

Intervention / Treatment
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* Drug: Docetaxel
* Drug: Cisplatin
* Drug: 5-fluorouracil
* Biological: Cetuximab Induction
* Biological: Cetuximab Radioimmunotherapy
* Radiation: Boost irradiation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed local advanced squamous cell carcinoma of the Larynx, Hypopharynx, Oropharynx or Cavum oris stage III and IV One measureable lesion (CT oder MR) Age 18 - 75 (including) Performance Score ECOG 0 - 1 Exclusion Criteria selected: Distant metastases ECOG Score >1 Prior radiation (Head and neck area) Creatinin Clearance below 60 ml/µl Acute infections Neuropathy grade 3 or 4 Myocardial Infarction within the last 12 months Acute coronary syndrome or othe clinically significant cardiovascular diseases

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: A<br>Patients receive 3 cycles (cycle duration 21 days) of docetaxel (75mg/m²), cisplatin (75mg/m²) and 5-fluorouracil (750mg/m²) followed by Cetuximab (weekly, starting with 400mg/m² then continuing with 250 mg/m²) with radiotherapy (concomitant boost for 6 weeks). Active comparator is 5-fluorouracil for first three cycles. | Drug: Docetaxel<br>* 75 mg/m² on day 1 of 21-days cycle<br>Drug: Cisplatin<br>* 75 mg/m² on day 1 of 21-days cycle<br>Drug: 5-fluorouracil<br>* 750 mg/m² day 1 to 5 during 24 hours of 21-days cycle<br>Biological: Cetuximab Radioimmunotherapy<br>* weekly, starting with 400 mg/m² during 120 min.(saturation only arm A) then continuing with 250 mg/m²; duration 7 weeks<br>* Other names: Erbitux;Radiation: Boost irradiation<br>* First 18 irradiations once daily with single dose of 1,8 Gy for 5 days per week. In addition by day 19 a second irradiation boost will be applied for further 12 days(1,5 Gy per day with at least 5 hours interval to 1,8 Gy dose. This results in total clinical target dose of 72 Gy and total subclinical target dose of 54 Gy. Duration of irradiation: 6 weeks<br>* Other names: Concomitant boost-irradiation;|
| Experimental: B<br>All patients receive 3 cycles (cycle duration 21 days) of docetaxel (75mg/m²), cisplatin (75mg/m²) Cetuximab (weekly, starting with 400mg/m² and continuing with 250 mg/m²), followed by Cetuximab (weekly 250 mg/m²) with radiotherapy (concomitant boost for 6 weeks). Experimental: cetuximab for the first three cycles. | Drug: Docetaxel<br>* 75 mg/m² on day 1 of 21-days cycle<br>Drug: Cisplatin<br>* 75 mg/m² on day 1 of 21-days cycle<br>Biological: Cetuximab Induction<br>* weekly, starting with 400 mg/m² during 120 min.(saturation) then continuing with 250 mg/m²; duration 3 cycles with 21 days<br>* Other names: Erbitux;Biological: Cetuximab Radioimmunotherapy<br>* weekly, starting with 400 mg/m² during 120 min.(saturation only arm A) then continuing with 250 mg/m²; duration 7 weeks<br>* Other names: Erbitux;Radiation: Boost irradiation<br>* First 18 irradiations once daily with single dose of 1,8 Gy for 5 days per week. In addition by day 19 a second irradiation boost will be applied for further 12 days(1,5 Gy per day with at least 5 hours interval to 1,8 Gy dose. This results in total clinical target dose of 72 Gy and total subclinical target dose of 54 Gy. Duration of irradiation: 6 weeks<br>* Other names: Concomitant boost-irradiation;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate (CR, PR) | RECIST criteria | 3 months after end of therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (CR, PR, PD, SD) | RECIST | until 3 months after therapy | 
| Locoregionally monitoring |  | after one year | 
| Progression Free Survival (PFS) |  | 1, 2 and 5 years after start of therapy | 
| Adverse reactions | Information about acute toxicity (grade, relation to study drug) during study treatment and until 3 months after end of radiotherapy will be collected for each patient using CTCAE 3.0 criteria list. Information about late toxicity (grade) will be collected after 3 months of radiotherapy and until 60 months after radiotherapy using RTOG/EORTC toxicity criteria. Kind and number of toxicities will be described according to grade. The highest grade of each patient and toxicity will be analysed. | During treatment and until 60 months after end of radiotherapy | 
| Overall-Survival |  | 1, 2 and 5 years after start of therapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Larynx, Cavum oris, local advanced squamous cell carcinoma, Hypopharynx, Oropharynx, docetaxel, cisplatin, 5-fluorouracil, Cetuximab