Induction Chemotherapy Comparing Taxotere® Cisplatin and 5-Fluorouracil (TPF) With Standard Cisplatin and 5-Fluorouracil (PF) Followed by Chemoradiation in Locally Advanced Head and Neck Cancer

Sponsor

Sanofi (Industry)

Overall Status

Completed

CT.gov ID

NCT00273546

Collaborator

(none)

500

Enrollment

Locations

81.1

Duration (Months)

83.3

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Cancer	Drug: XRP6976 (Docetaxel/Taxotere)	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

500 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Study Start Date :

May 1, 1999

Actual Primary Completion Date :

Feb 1, 2006

Actual Study Completion Date :

Feb 1, 2006

Outcome Measures

Primary Outcome 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 Outcome 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. []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sanofi-Aventis Administrative Office	Bridgewater	New Jersey	United States	08807
2	Sanofi-Aventis Administrative Office	Buenos Aires		Argentina
3	Sanofi-Aventis Administrative Office	Laval		Canada
4	Sanofi-Aventis Administrative Office	Paris		France
5	Sanofi-Aventis Administrative Office	Porto Salvo		Portugal
6	Sanofi-Aventis Administrative Office	Moscow		Russian Federation