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

Phase 2

Completed

• Conditions: Larynx Cancer; Hypopharynx Cancer

• Registration Number: NCT00169247
• Lead Sponsor: Groupe Oncologie Radiotherapie Tete et Cou

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2005-09-12
• Study First Submitted QC: 2005-09-12
• Study First Posted: 2005-09-15
• Study Start: 2005-10
• Primary Completion: 2011-04
• Status Verified: 2011-06
• Last Update Submitted: 2011-06-23
• Last Update Posted: 2011-06-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 156

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
rate of laryngeal preservation

Secondary Outcome Measures

Name	Time	Method
quality of life

Trial Locations

Locations (3)

Centre Oscar Lambret; 🇫🇷 Lille, France

Centre René Gauducheau; 🇫🇷 Nantes, France

CHU de Tours; 🇫🇷 Tours, France