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

Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00273546
• Other study ID #: EFC6043
• Secondary ID: RP-56976-V-324
• Status: Completed
• Phase: Phase 3
• First received: January 6, 2006
• Last updated: April 28, 2009
• Start date: May 1999
• Est. completion date: February 2006

Study information

• Verified date: April 2009
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Other known NCT identifiers

• NCT00004214

Recruitment information / eligibility

• Status: Completed
• Enrollment: 500
• Est. completion date: February 2006
• Est. primary completion date: February 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cancer
• Head and Neck Neoplasms

Intervention

Drug:
• XRP6976 (Docetaxel/Taxotere)

Locations

Country	Name	City	State
Argentina	Sanofi-Aventis Administrative Office	Buenos Aires
Canada	Sanofi-Aventis Administrative Office	Laval
France	Sanofi-Aventis Administrative Office	Paris
Portugal	Sanofi-Aventis Administrative Office	Porto Salvo
Russian Federation	Sanofi-Aventis Administrative Office	Moscow
United States	Sanofi-Aventis Administrative Office	Bridgewater	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Argentina,  Canada,  France,  Portugal,  Russian Federation, 

References & Publications (1)

Posner MR, Hershock DM, Blajman CR, Mickiewicz E, Winquist E, Gorbounova V, Tjulandin S, Shin DM, Cullen K, Ervin TJ, Murphy BA, Raez LE, Cohen RB, Spaulding M, Tishler RB, Roth B, Viroglio Rdel C, Venkatesan V, Romanov I, Agarwala S, Harter KW, Dugan M, — View Citation

Outcome

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