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 Oral Cavity Stage III, Squamous Cell Carcinoma of the Oral Cavity Stage IV, Squamous Cell Carcinoma of the Oropharynx Stage III, Squamous Cell Carcinoma of the Oropharynx Stage IV
Conditions
Keywords
local advanced squamous cell carcinoma, Larynx, Hypopharynx, Oropharynx, Cavum oris, docetaxel, cisplatin, 5-fluorouracil, Cetuximab
Brief summary
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
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.
Interventions
DRUGDocetaxel
75 mg/m² on day 1 of 21-days cycle
DRUGCisplatin
75 mg/m² on day 1 of 21-days cycle
DRUG5-fluorouracil
750 mg/m² day 1 to 5 during 24 hours of 21-days cycle
BIOLOGICALCetuximab Induction
weekly, starting with 400 mg/m² during 120 min.(saturation) then continuing with 250 mg/m²; duration 3 cycles with 21 days
BIOLOGICALCetuximab Radioimmunotherapy
weekly, starting with 400 mg/m² during 120 min.(saturation only arm A) then continuing with 250 mg/m²; duration 7 weeks
RADIATIONBoost irradiation
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
Sponsors
Arbeitsgemeinschaft medikamentoese Tumortherapie
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate (CR, PR) | 3 months after end of therapy | RECIST criteria |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (CR, PR, PD, SD) | until 3 months after therapy | RECIST |
| Locoregionally monitoring | after one year | — |
| Progression Free Survival (PFS) | 1, 2 and 5 years after start of therapy | — |
| Adverse reactions | During treatment and until 60 months after end of radiotherapy | 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. |
| Overall-Survival | 1, 2 and 5 years after start of therapy | — |
Countries
Austria
Outcome results
None listed