Taxotere (Docetaxel) New Indication: Squamous Cell Carcinoma of the Head and Neck (SCCHN) Treatment Registration Trial

Study Overview
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Brief Summary
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The Primary Objective is to evaluate the progression-free survival after treatment with docetaxel plus cisplatin plus 5-Fluorouracil (5-FU) (DCF) in comparison with cisplatin plus 5-FU (CF) in patient with locally advanced inoperable SCCHN The Secondary Objective is to evaluate and compare the clinical response rate both before and after radiotherapy, the local symptoms, the duration of response, the time to treatment failure, the survival, the toxicity and the quality of life in the 2 study groups.

Official Title
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An Open-label, Randomized, Parallel-group, Multicenter Study of Neoadjuvant Docetaxel(Taxotere®) Plus Cisplatin Plus 5-fluorouracil Versus Neoadjuvant Cisplatin Plus 5-fluorouracil in Patients With Locally Advanced Inoperable Squamous Cell Carcinoma of the Head and Neck

Conditions
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Head and Neck Neoplasms

Intervention / Treatment
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* Drug: DOCETAXEL
* Drug: CISPLATIN
* Drug: 5-FLUOROURACIL


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Tumor type: Histologically or cytologically proven squamous cell carcinoma of the head and neck (SCCHN) presenting with locally advanced disease at diagnosis. Primary tumor sites eligible are: oral cavity, oropharynx, hypopharynx and larynx. Extent of the disease: Patients are required to have at least one measurable lesion. Stage III or IV without evidence of distant metastases, according to the TNM staging system. Absence of metastases must be checked by chest X-ray (with or without Computed tomography (CT) ), abdominal ultrasound or CT in case of liver function test abnormalities, and bone scan in case of local symptoms. Tumor considered as inoperable after evaluation by a multidisciplinary team. Reason for inoperability will be reported in the CRF World Health Organization (WHO) performance status 0 or 1 Laboratory data: Haematology: Neutrophil count > or = 2.0*10^9/L Platelet count > or = 100*10^9/L Hemoglobin > or = 10 g/dl (6.2 mmol/L) Hepatic function: Total serum bilirubin < or = 1 time the upper normal limit (UNL) of the participating center Aspartate transaminase (ASAT/SGOT) and Alanine transaminase (ALAT/SGPT) < or = 2.5UNL Alkaline phosphatase < or = 5 UNL Patients with ASAT or ALAT > 1.5UNL associated with alkaline phosphatase >2.5UNL are not eligible for the study Renal function: serum creatinine < or = 120µmol/L (1.4 mg/dl) if values are >120µmol/L, creatinine clearance should be > or = 60 ml/min Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule, those conditions should be discussed with the patient before registration in the trial Patients informed consent form obtained Exclusion criteria: Tumors of the nasopharynx, the nasal and paranasal cavities. Previous chemotherapy or radiotherapy for any reason and previous surgery for SCCHN at time of study entry. Prior treatment within a therapeutic clinical tria within 30 days prior to study entry Concurrent treatment with any other anticancer therapy Chronic treatment (> or = 3 months) with corticosteroids at a daily dose > or = 20mg methylprednisolone or equivalent. Concomitant use of drugs which could interact with 5-fluorouracil (e.g. cimetidine, allopurinol, folic or folinic acid, methotrexate and metronidazole) Previous or current malignancies at other sites with the exception of adequately treated in situ carcinoma of the cervix uteri, basal or squamous cell carcinoma of the skin or other cancer curatively treated by surgery and with no evidence of disease for at least 5 years Symptomatic peripheral neuropathy > or = grade 2 by NCIC-CTG criteria Clinical altered hearing Pregnant, lactating women or of childbearing potential unless adequate with other serious illness or medical condition including but not limited to: unstable cardiac disease despite treatment myocardial infarction within 6 months prior to study entry history of significant neurologic or psychiatric disorders including dementia or seizures active uncontrolled infection active peptic ulcer chronic obstructive pulmonary disease requiring hospitalization during the year preceding study entry The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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 |
| --- | --- |
| Experimental: Docetaxel Cisplatin 5-Fluorouracil (DCF)<br>4 cycles of the following products every 3 weeks (unless disease progression/relapse or unacceptable toxicity occured or the patient refused treatment): Docetaxel 60mg/m² on day 1 Cisplatin 75mg/m² on day 1 5-FU 750mg/m²/day on day 1 to day 5 | Drug: DOCETAXEL<br>* Intravenous<br>Drug: CISPLATIN<br>* Intravenous<br>Drug: 5-FLUOROURACIL<br>* Intravenous<br>|
| Experimental: Cisplatin 5-Fluorouracil (CF)<br>4 cycles of the following products every 3 weeks (unless disease progression/relapse or unacceptable toxicity occured or the patient refused treatment): Cisplatin 75mg/m² on day 1 5-FU 750mg/m²/day on day 1 to day 5 | Drug: CISPLATIN<br>* Intravenous<br>Drug: 5-FLUOROURACIL<br>* Intravenous<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival |  | From randomization to any progression event or patient death (follow-up every 3 months 1st year, then every 6 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | From randomization to patient death (follow-up every 3 months 1st year, then every 6 months) | 
| Overall response rates |  | From randomization to any progression event or patient death (follow-up every 3 months 1st year, then every 6 months) and at the end of chemotherapy + end of radiotherapy | 
| Duration of response |  | From randomization to any progression event or patient death (follow-up every 3 months 1st year, then every 6 months) | 
| Time to treatment failure |  | From randomization to any progression event or patient death (follow-up every 3 months 1st year, then every 6 months) and at the end of chemotherapy + end of radiotherapy |