Clinical trial NCT00169247: Radiotherapy With Cisplatin Versus Radiotherapy With Cetuximab After Induction Chemotherapy for Larynx Preservation
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Larynx Cancer
Hypopharynx Cancer
Keywords: larynx cancer
hypopharynx cancer
larynx preservation
concomitant radiochemotherapy
cisplatin
cetuximab
randomized trial
Lead sponsor: Groupe Oncologie Radiotherapie Tete et Cou
Sponsor class: OTHER
Collaborators: name: Tumor Study Group Head and Neck
First posted: 2005-09-15
Enrollment: 156
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: rate of laryngeal preservation
Secondary outcomes:
measure: quality of life
Other outcomes:
Locations:
city: Lille
country: France
facility: Centre Oscar Lambret
city: Nantes
country: France
facility: Centre René Gauducheau
city: Tours
country: France
facility: CHU de Tours
Study officials:
affiliation: Centre Oscar Lambret
name: Jean-Louis Lefebvre
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lefebvre JL, Pointreau Y, Rolland F, Alfonsi M, Baudoux A, Sire C, de Raucourt D, Malard O, Degardin M, Tuchais C, Blot E, Rives M, Reyt E, Tourani JM, Geoffrois L, Peyrade F, Guichard F, Chevalier D, Babin E, Lang P, Janot F, Calais G, Garaud P, Bardet E. Induction chemotherapy followed by either chemoradiotherapy or bioradiotherapy for larynx preservation: the TREMPLIN randomized phase II study. J Clin Oncol. 2013 Mar 1;31(7):853-9. doi: 10.1200/JCO.2012.42.3988. Epub 2013 Jan 22.