Combination Chemotherapy Plus Radiation Therapy in Treating Patients With Advanced Head and Neck Cancer

Head and Neck Cancer Clinical Trial

Official title:

A Randomized Phase III Multicenter Trial 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00003888
• Other study ID #: EORTC-24971
• Secondary ID: RP-56976-V-323
• Status: Completed
• Phase: Phase 3
• Start date: April 1999
• Est. completion date: March 2015

Study information

• Verified date: July 2015
• Source: European Organisation for Research and Treatment of Cancer - EORTC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining more than one drug and combining chemotherapy with radiation therapy may kill more tumor cells. It is not yet known which regimen of combination chemotherapy is more effective for advanced head and neck cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of two regimens of combination chemotherapy plus radiation therapy in treating patients who have advanced head and neck cancer.

Description:

OBJECTIVES: I. Compare the progression free survival of patients with locally advanced, inoperable squamous cell carcinoma of the head and neck treated with cisplatin plus fluorouracil with or without docetaxel as a neoadjuvant to radiotherapy. II. Compare the response rate, response duration, toxicity, local symptoms, and time to disease progression of these treatment regimens in this patient population. III. Evaluate the quality of life in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to primary tumor site (oral cavity vs oropharynx vs hypopharynx vs larynx) and institution. Patients are randomized to one of two treatment arms. Arm I: Patients receive docetaxel IV over 1 hour, immediately followed by cisplatin IV over 1 hour on day 1 and fluorouracil (5-FU) IV as a continuous infusion on days 1-5. Arm II: Patients receive cisplatin IV over 1 hour on day 1 followed by 5-FU IV as a continuous infusion on days 1-5. Treatment continues every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Patients receive radiotherapy following chemotherapy within 3-6 weeks of last course. Radiotherapy is administered 5 days a week for up to 7 weeks. Quality of life is assessed before treatment, at courses 2 and 4, and at 6 and 9 months. Patients are followed every 3 months for the first 2 years and then every 6 months until death.

PROJECTED ACCRUAL: A total of 348 patients will be accrued for this study within 24 months.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 359
• Est. completion date: March 2015
• Est. primary completion date: March 2002
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

DISEASE CHARACTERISTICS: Histologically or cytologically proven locally advanced squamous cell carcinoma of the head and neck Stage III or IV without distant metastases Unresectable Primary tumor sites: Oral cavity Oropharynx Hypopharynx Larynx Must have at least one measurable lesion

PATIENT CHARACTERISTICS: Age: 18 to 70 Performance status: WHO 0-1 Life expectancy: Not specified Hematopoietic: Absolute neutrophil count at least 2,000/mm3 Platelet count at least 100,000/mm3 Hemoglobin at least 10 g/dL Hepatic: Bilirubin no greater than upper limit of normal (ULN) SGOT and SGPT no greater than 2.5 times ULN Alkaline phosphatase no greater than 5 times ULN No SGOT and SGPT greater than 1.5 times ULN AND alkaline phosphatase greater than 2.5 times ULN Renal: Creatinine no greater than 1.4 mg/dL OR Creatinine clearance at least 60 mL/min Cardiovascular: At least 6 months since prior myocardial infarction No unstable, treated cardiac disease Pulmonary: At least one year since prior hospitalization for chronic obstructive pulmonary disease Neurologic: No neurologic or psychiatric disorders (e.g., dementia or seizures) No concurrent peripheral neuropathy greater than grade 1 Other: No active uncontrolled infection No active peptic ulcer No alteration in hearing At least 5 years since any other neoplastic disease except curatively treated basal or squamous cell skin cancer, carcinoma in situ of the cervix, or other cancer curatively treated by surgery Not pregnant or nursing Fertile patients must use effective contraception No other psychological, familial, sociological, or geographical condition that would prevent compliance

PRIOR CONCURRENT THERAPY: Biologic therapy: No primary prophylactic colony stimulating factors during the first course of therapy Chemotherapy: No prior or concurrent chemotherapy Endocrine therapy: At least 3 weeks since prior corticosteroid No chronic corticosteroid therapy (greater than 3 months) Radiotherapy: No prior radiotherapy Surgery: No prior surgery for this cancer Other: At least 30 days since prior treatment in a clinical trial No concurrent use of drugs that interact with fluorouracil (e.g., cimetidine, allopurinol, folic acid or leucovorin calcium) No other concurrent investigational drugs or anticancer treatment

Related Conditions & MeSH terms

• Carcinoma, Squamous Cell
• Head and Neck Cancer
• Head and Neck Neoplasms

Intervention

Drug:
• cisplatin

• docetaxel

• fluorouracil

Radiation:
• radiation therapy

Locations

Country	Name	City	State
Austria	Landeskrankenhaus/Universitatskliniken Graz	Graz
Austria	Allgemeines Krankenhaus der Stadt Wien	Vienna
Austria	Kaiser Franz Josef Hospital	Vienna
Belgium	Algemeen Ziekenhuis Middelheim	Antwerp
Belgium	Institut Jules Bordet	Brussels
Belgium	Universitair Ziekenhuis Antwerpen	Edegem
Belgium	Centre Hospitalier Regional de la Citadelle	Liege
Belgium	Clinique Universitaire De Mont-Godinne	Mont-Godinne Yvoir
Former Yugoslavia	Institute of Oncology and Radiology of Serbia	Belgrade
France	CHR de Besancon - Hopital Jean Minjoz	Besancon
France	Centre Oscar Lambret	Lille
France	Centre Hospital Regional Universitaire de Limoges	Limoges
France	Centre Leon Berard	Lyon
France	CHR Hotel Dieu	Nantes
France	CRLCC Nantes - Atlantique	Nantes-Saint Herblain
France	Centre Antoine Lacassagne	Nice
Germany	Martin Luther Universitaet	Halle
Germany	Caritasklinik St. Theresia	Saarbrucken
Germany	Mutterhaus der Borromaerinnen	Trier
Greece	Ahepa University Hospital	Thessaloniki
Hungary	National Institute of Oncology	Budapest
Hungary	Szent Margit Hospital	Budapest
Hungary	Borsod-Abauj-Zemplen County Hospital	Miskolc
Italy	Centro di Riferimento Oncologico - Aviano	Aviano
Italy	Ospedale Santa Croce	Cuneo
Italy	Istituti Fisioterapici Ospitalieri - Roma	Rome
Italy	Ospedale di Circolo e Fondazione Macchi	Varese
Netherlands	Academisch Medisch Centrum	Amsterdam
Netherlands	Leiden University Medical Center	Leiden
Netherlands	Academisch Ziekenhuis Maastricht	Maastricht
Netherlands	University Medical Center Nijmegen	Nijmegen
Poland	Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology	Warsaw
Slovakia	National Cancer Institute - Bratislava	Bratislava
Spain	Institut Catala d'Oncologia - Hospital Duran i Reynals	Barcelona
Spain	Hospital General de Jerez	Jerez
Spain	Universidad de Santiago - Hospital de Conxo	Santiago de Compostela
Spain	Hospital Clinico Universitario de Valencia	Valencia
Switzerland	Kantonspital Aarau	Aarau
Switzerland	Ospedale San Giovanni	Bellinzona
Turkey	Istanbul University-Institute of Oncology	Istanbul
United Kingdom	Beatson Oncology Centre	Glasgow	Scotland
United Kingdom	Charing Cross Hospital	London	England
United Kingdom	Middlesex Hospital- Meyerstein Institute	London	England
United Kingdom	Newcastle General Hospital	Newcastle Upon Tyne	England

Sponsors (1)

Lead Sponsor	Collaborator
European Organisation for Research and Treatment of Cancer - EORTC

Countries where clinical trial is conducted

Austria,  Belgium,  Former Yugoslavia,  France,  Germany,  Greece,  Hungary,  Italy,  Netherlands,  Poland,  Slovakia,  Spain,  Switzerland,  Turkey,  United Kingdom, 

References & Publications (6)

Bernier J, Coens C, Remenar E, et al.: Impact on quality of life (QoL) of the addition of docetaxel (T) to neoadjuvant cisplatin plus 5-fluorouracil treatment in patients with locally advanced unresectable squamous cell carcinoma of the head and neck (SCC

Jansen J, Vermorken JB, Boote D, et al.: Cost-effectiveness analysis of the EORTC 24971 (TAX 323) trial comparing docetaxel plus cisplatin and 5-fluorouracil versus standard treatment (cisplatin and 5-fluorouracil) as induction chemotherapy followed by radiation therapy in locally advanced unresectable squamous cell carcinoma of the head and neck (SCCHN). [Abstract] J Clin Oncol 25 (Suppl 18): A-6090, 321s, 2007.

Remenar E, Van Herpen C, Lluch JG, et al.: A randomized phase III multicenter trial of neoadjuvant docetaxel plus cisplatin and 5-fluorouracil (TPF) versus neoadjuvant PF in patients with locally advanced unresectable squamous cell carcinoma of the head a

van Herpen CM, Mauer ME, Mesia R, Degardin M, Jelic S, Coens C, Betka J, Bernier J, Remenar E, Stewart JS, Preiss JH, van den Weyngaert D, Bottomley A, Vermorken JB; EORTC Head and Neck Group. Short-term health-related quality of life and symptom control — View Citation

Vermorken JB, Remenar E, Van Herpen C, et al.: Standard cisplatin/infusional 5-fluorouracil (PF) vs docetaxel (T) plus PF (TPF) as neoadjuvant chemotherapy for nonresectable locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN): a phase

Vermorken JB, Remenar E, van Herpen C, Gorlia T, Mesia R, Degardin M, Stewart JS, Jelic S, Betka J, Preiss JH, van den Weyngaert D, Awada A, Cupissol D, Kienzer HR, Rey A, Desaunois I, Bernier J, Lefebvre JL; EORTC 24971/TAX 323 Study Group. Cisplatin, fl — View Citation