Official Title: “A Randomized Phase III Multicenter Trial of Neoadjuvant Docetaxel (Taxotere®) Plus Cisplatin and 5-Fluorouracil (TPF) Versus Neoadjuvant Cisplatin Plus 5-Fluorouracil Followed by Concomitant Chemoradiotherapy to Improve the Overall Survival and Progression Free Survival in Patients With Locally Advanced Squamous Cell Carcinoma of the Head and Neck”

- 1.To compare overall survival after treatment with the test tri-therapy (TPF: docetaxel plus cisplatin and 5FU) or the control treatment (PF: cisplatin plus 5-FU) followed by chemoradiotherapy in patients with locally advanced SCCHN. - 2.The main secondary endpoint is progression free survival (PFS). The other secondary endpoints are to evaluate and compare improvement of local symptoms; time-to-treatment failure; quality of life; clinical complete response rate (CR and CR/PR); toxicity and to evaluate the relationship of tumor markers and response to therapy.

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: February 2006

Intervention(s) in this Clinical Trial

• Drug: XRP6976 (Docetaxel/Taxotere)

Primary Measures

• Overall survival after treatment with the test tri-therapy (TPF: docetaxel plus cisplatin and 5-FU) or the control treatment (PF: Cisplatin plus 5-FU) followed by chemoradiotherapy.

Secondary Measures

• The main secondary outcome is progression free survival (PFS).
• The other secondary endpoints are improvement of local symptoms;time-to-treatment failure;quality of life;
• clinical complete response rate (CR) and overall response rate(PR+CR) after chemotherapy and after locoregional therapy(chemoradiotherapy);
• duration of response(CR and CR+PR); toxicity.

Inclusion Criteria:

• 1.Histologically or cytologically proven squamous cell carcinoma of the head/neck.
• 2.Primary tumor sites eligible: oral cavity, oropharynx, hypopharynx, larynx.
• Although they are admittedly of squamous cell types, the following tumors will be excluded because their responsiveness to chemotherapy may differ: nasal, paranasal cavities; nasopharynx.
• 3.Stage 3 or 4 disease without evidence of distant metastases verified with Chest
• X-Ray, abdominal ultrasound or CT (liver function test abnormalities); bone scan in case of local symptoms.
• 4.At least one uni or bidimensionally measurable lesion.
• 5.Tumor considered as inoperable after evaluation by a multidisciplinary team (surgeon, medical oncologist and radiation oncologist). Criteria include : Technical unresectablility-ie tumor fixation/invasion to base of the skull or cervical vertebrae involvement of the nasopharynx and fixed lymph nodes; Physician's decision based on low surgical curability which includes all T3-4 stages, all N2-3 stages excluding
• T1N2; organ preservation.
• 6.No previous chemotherapy or radiotherapy for any reason and no previous surgery for
• SCCHN (other than biopsy) are allowed at time of study entry.
• 7.Age ³ 18 years.
• 8.WHO performance status of 0-1
• 9.No active alcohol addiction
• 10.Life expectancy ³ 12 weeks
• 11.Signed informed consent prior to beginning protocol specific procedures
• 12.Adequate bone marrow, hepatic and renal functions as evidenced by the following:
• Hematology (Bone Marrow): Neutrophil count ³ 2.0 x 10 9/L; Platelet count ³ 100 X 10 9/L; Hemoglobin ³ 10g/dL; Hepatic function : Total bilirubin WNL; ASAT (SGOT) and ALAT (SGPT) £ 2.5 X ULN; Alkaline phosphatase £ 5 X ULN; patients with ASAT or ALAT > 1.5 x
• ULN associated with alkaline phosphatase > 2.5 x ULN are not eligible for the study;
• Renal function: the creatinine clearance ³ 60 ml/min (actual or calculated by the Cockcroft-Gault method as follows: Weight (kg) X (140-age)/K x serum creatinine.
• 13.Patients must be available for treatment and follow up. Patients registered on this trial must be treated and followed at the participating center.

Exclusion Criteria:

• 1.Pregnant or lactating women or women of childbearing potential not using adequate contraception.
• 2.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. Any prior treatment with radiotherapy or chemotherapy is an exclusion criterion.
• 3.Symptomatic peripheral neuropathy ³ grade 2 by NCIC-CTG criteria.
• 4.Symptomatic altered hearing > grade 2 by NCIC-CTG criteria.
• 5.Other serious illnesses or medical conditions including but no 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;
• Hypercalcemia; Chronic obstructive pulmonary disease requiring hospitalization during the year preceding study entry.
• 6.Patients requiring intravenous alimentation.
• 7.Patients who experienced a weight loss of more than 20% of their body weight in the 3 months preceding study entry.
• 8.Concurrent treatment with any other anticancer therapy
• 9.Participation in an investigational trial within 30 days of study entry.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Sanofi-Aventis

Overall Clinical Trial Officials and Contacts

Marshall Posner, MD Study Chair Dana-Farber Cancer Institute  

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00273546

Study ID Number: EFC6043

ClinicalTrials.gov Identifier: NCT00273546

Health Authority: United States: Food and Drug Administration