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

NCT ID: NCT00003888

Last Updated: 2018-07-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 359 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1999-04-30
• Study Completion Date: 2015-03-31

Brief 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.

Detailed 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.

Conditions

Head and Neck Cancer

Study Design

• Allocation Method: RANDOMIZED
• Primary Study Purpose: TREATMENT

Interventions

cisplatin

Intervention Type: DRUG

docetaxel

Intervention Type: DRUG

fluorouracil

Intervention Type: DRUG

radiation therapy

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

European Organisation for Research and Treatment of Cancer - EORTC

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jan B. Vermorken, MD, PhD

Role: STUDY_CHAIR

University Hospital, Antwerp

Locations

Landeskrankenhaus/Universitatskliniken Graz

Graz, , Austria

Allgemeines Krankenhaus der Stadt Wien

Vienna, , Austria

Kaiser Franz Josef Hospital

Vienna, , Austria

Algemeen Ziekenhuis Middelheim

Antwerp, , Belgium

Institut Jules Bordet

Brussels, , Belgium

Universitair Ziekenhuis Antwerpen

Edegem, , Belgium

Centre Hospitalier Regional de la Citadelle

Liège, , Belgium

Clinique Universitaire De Mont-Godinne

Mont-Godinne Yvoir, , Belgium

Institute of Oncology and Radiology of Serbia

Belgrade, , Federal Republic of Yugoslavia

CHR de Besancon - Hopital Jean Minjoz

Besançon, , 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, , France

Martin Luther Universitaet

Halle, , Germany

Caritasklinik St. Theresia

Saarbrücken, , Germany

Mutterhaus der Borromaerinnen

Trier, , Germany

Ahepa University Hospital

Thessaloniki, , Greece

National Institute of Oncology

Budapest, , Hungary

Szent Margit Hospital

Budapest, , Hungary

Borsod-Abauj-Zemplen County Hospital

Miskolc, , Hungary

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, , Italy

Academisch Medisch Centrum

Amsterdam, , Netherlands

Leiden University Medical Center

Leiden, , Netherlands

Academisch Ziekenhuis Maastricht

Maastricht, , Netherlands

University Medical Center Nijmegen

Nijmegen, , Netherlands

Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology

Warsaw, , Poland

National Cancer Institute - Bratislava

Bratislava, , Slovakia

Institut Catala d'Oncologia - Hospital Duran i Reynals

Barcelona, , Spain

Hospital General de Jerez

Jerez de la Frontera, , Spain

Universidad de Santiago - Hospital de Conxo

Santiago de Compostela, , Spain

Hospital Clinico Universitario de Valencia

Valencia, , Spain

Kantonspital Aarau

Aarau, , Switzerland

Ospedale San Giovanni

Bellinzona, , Switzerland

Istanbul University-Institute of Oncology

Istanbul, , Turkey (Türkiye)

Charing Cross Hospital

London, England, United Kingdom

Middlesex Hospital- Meyerstein Institute

London, England, United Kingdom

Newcastle General Hospital

Newcastle upon Tyne, England, United Kingdom

Beatson Oncology Centre

Glasgow, Scotland, United Kingdom

Countries

Austria; Belgium; Federal Republic of Yugoslavia; France; Germany; Greece; Hungary; Italy; Netherlands; Poland; Slovakia; Spain; Switzerland; Turkey (Türkiye); United Kingdom

References

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.

Reference Type: BACKGROUND

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 with docetaxel, cisplatin, 5-fluorouracil and cisplatin (TPF), 5-fluorouracil (PF) for induction in unresectable locoregionally advanced head and neck cancer patients (EORTC 24971/TAX 323). Br J Cancer. 2010 Oct 12;103(8):1173-81. doi: 10.1038/sj.bjc.6605860. Epub 2010 Sep 14.

Reference Type: RESULT

PMID: 20842129 (View on PubMed)

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, fluorouracil, and docetaxel in unresectable head and neck cancer. N Engl J Med. 2007 Oct 25;357(17):1695-704. doi: 10.1056/NEJMoa071028.

Reference Type: RESULT

PMID: 17960012 (View on PubMed)

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 (SCCHN): EORTC study 24971. [Abstract] J Clin Oncol 24 (Suppl 18): A-5522, 285s, 2006.

Reference Type: RESULT

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 and neck (SCCHN). Final analysis of EORTC 24971. [Abstract] J Clin Oncol 24 (Suppl 18): A-5516, 2006.

Reference Type: RESULT

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 III trial of the EORTC Head and Neck Cancer Group (EORTC #24971). [Abstract] J Clin Oncol 22 (Suppl 14): A-5508, 490s, 2004.

Reference Type: RESULT

Other Identifiers

RP-56976-V-323

Identifier Type: -

Identifier Source: secondary_id

EORTC-24971

Identifier Type: -

Identifier Source: org_study_id