Radiotherapy With Cisplatin Versus Radiotherapy With Cetuximab After Induction Chemotherapy for Larynx Preservation

Study Overview
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Brief Summary
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Larynx preservation remains a very challenging approach in patients with larynx/pharynx cancer. A first attempt consisted of induction chemotherapy followed in good responders by irradiation. This approach allowed to preserve 60 % of the larynx without any significant difference in survival. The second attempt consisted of concurrent chemo-irradiation. This approach provided a higher larynx preservation rate but survival remained unchanged and mucosal toxicity was also higher. A third approach is currently under evaluation: induction chemotherapy followed by concurrent chemo-irradiation in good responders.

Detailed Description
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At ASCO 2004 there were 3 major presentations issuing an increasing in survival: the update of the MACH-NC meta-analysis showed that actually only concurrent chemo-irradiation trials found a significantly improved survival (in particular the addition of cisplatinum alone to radiotherapy) the addition of docetaxel to the cisplatinum-5FU regimen (TPF) when compared with cisplatinum--5FU (PF) the addition of cetuximab to irradiation On this basis we decided to carry-out a randomized phase II for previously untreated patients requiring a total laryngectomy: All patients after a complete work-up including a CTscan will receive 3 cycles of TPF(T: 75 mg/m², P: 75 mg/m² and 5FU 750 mg/m²). Patients with response over 50 % (endoscopy and CTscan) will be randomized to receive either irradiation (70 Gy) and cisplatinum (100 mg/m² on D1, D22 and D43) or irradiation (70 Gy) with cetuximab (loading dose of 400 mg followed by weekly 250 mg for a total of 8 cycles. Patients with less than 50% decease in tumour volume after TPF, patients with residual or recurrent disease after either RT-CDDP or RT-cetuximab will get salvage total laryngectomy.

Official Title
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Larynx Preservation With Induction Chemotherapy (Cisplatin, 5FU, Docetaxel) Followed by Radiotherapy Combined With Either Cisplatin or Cetuximab in Laryngopharyngeal Squamous Cell Carcinoma - A Randomised Phase II Study

Conditions
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Larynx Cancer, Hypopharynx Cancer

Intervention / Treatment
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* Drug: cetuximab
* Drug: Cisplatin
* Procedure: Radiotherapy 70 Gy, 35 fractions


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Larynx or hypopharynx squamous cell carcinoma proven by histology, locally advanced, only eligible for surgery as total or sub-total (pharyngo-)laryngectomy Performance status 0-1 Neutrophils >=1.5 x 109/l, Platelets count >=100 x 109/l, haemoglobin >=10 g/dl Total bilirubin <= 1.5 x upper reference range ASAT and ALAT <= 2.5 x upper reference range, Alkaline Phosphatases <= 5 x upper reference range Serum creatinine <= 120 µmol/l Weight loss < 10 % within last 3 months Written inform consent Exclusion Criteria: Infiltrative transglottic tumor or clinical cartilage invasion Distant metastasis Previous chemotherapy or radiotherapy Contra-indication to chemotherapy

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

| Intervention/Treatment |
| --- |
|Drug: cetuximab|nan|
|Drug: Cisplatin|nan|
|Procedure: Radiotherapy 70 Gy, 35 fractions|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| rate of laryngeal preservation |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| quality of life |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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larynx cancer, hypopharynx cancer, larynx preservation, concomitant radiochemotherapy, cisplatin, cetuximab, randomized trial