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

Sponsor

European Organisation for Research and Treatment of Cancer - EORTC (Other)

Overall Status

Completed

CT.gov ID

NCT00003888

Collaborator

(none)

359

Enrollment

Locations

191

Duration (Months)

8.2

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Head and Neck Cancer	Drug: cisplatin Drug: docetaxel Drug: fluorouracil Radiation: radiation therapy	Phase 3

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

359 participants

Allocation:

Randomized

Primary Purpose:

Treatment

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

Study Start Date :

Apr 1, 1999

Actual Primary Completion Date :

Mar 1, 2002

Actual Study Completion Date :

Mar 1, 2015

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Landeskrankenhaus/Universitatskliniken Graz	Graz		Austria	A-8036
2	Allgemeines Krankenhaus der Stadt Wien	Vienna		Austria	A-1090
3	Kaiser Franz Josef Hospital	Vienna		Austria	A-1100
4	Algemeen Ziekenhuis Middelheim	Antwerp		Belgium	2020
5	Institut Jules Bordet	Brussels		Belgium	1000
6	Universitair Ziekenhuis Antwerpen	Edegem		Belgium	B-2650
7	Centre Hospitalier Regional de la Citadelle	Liege		Belgium	4000
8	Clinique Universitaire De Mont-Godinne	Mont-Godinne Yvoir		Belgium	5530
9	Institute of Oncology and Radiology of Serbia	Belgrade		Former Yugoslavia	11000
10	CHR de Besancon - Hopital Jean Minjoz	Besancon		France	25030
11	Centre Oscar Lambret	Lille		France	59020
12	Centre Hospital Regional Universitaire de Limoges	Limoges		France	87042
13	Centre Leon Berard	Lyon		France	69373
14	CRLCC Nantes - Atlantique	Nantes-Saint Herblain		France	44805
15	CHR Hotel Dieu	Nantes		France	44093
16	Centre Antoine Lacassagne	Nice		France	06189
17	Martin Luther Universitaet	Halle		Germany	DOH-0-6112
18	Caritasklinik St. Theresia	Saarbrucken		Germany	D-66113
19	Mutterhaus der Borromaerinnen	Trier		Germany	D-54219
20	Ahepa University Hospital	Thessaloniki		Greece	54636
21	National Institute of Oncology	Budapest		Hungary	1125
22	Szent Margit Hospital	Budapest		Hungary	3761
23	Borsod-Abauj-Zemplen County Hospital	Miskolc		Hungary	3501
24	Centro di Riferimento Oncologico - Aviano	Aviano		Italy	33081
25	Ospedale Santa Croce	Cuneo		Italy	12100
26	Istituti Fisioterapici Ospitalieri - Roma	Rome		Italy	00161
27	Ospedale di Circolo e Fondazione Macchi	Varese		Italy	21100
28	Academisch Medisch Centrum	Amsterdam		Netherlands	1105 AZ
29	Leiden University Medical Center	Leiden		Netherlands	2300 CA
30	Academisch Ziekenhuis Maastricht	Maastricht		Netherlands	6202 AZ
31	University Medical Center Nijmegen	Nijmegen		Netherlands	NL-6500 HB
32	Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology	Warsaw		Poland	02-781
33	National Cancer Institute - Bratislava	Bratislava		Slovakia	833 10
34	Institut Catala d'Oncologia - Hospital Duran i Reynals	Barcelona		Spain	08907
35	Hospital General de Jerez	Jerez		Spain	11407
36	Universidad de Santiago - Hospital de Conxo	Santiago de Compostela		Spain
37	Hospital Clinico Universitario de Valencia	Valencia		Spain	46010
38	Kantonspital Aarau	Aarau		Switzerland	5001
39	Ospedale San Giovanni	Bellinzona		Switzerland	CH-6500
40	Istanbul University-Institute of Oncology	Istanbul		Turkey	34390
41	Charing Cross Hospital	London	England	United Kingdom	W6 8RF
42	Middlesex Hospital- Meyerstein Institute	London	England	United Kingdom	WIT 3AA
43	Newcastle General Hospital	Newcastle Upon Tyne	England	United Kingdom	NE4 6BE
44	Beatson Oncology Centre	Glasgow	Scotland	United Kingdom	G11 6NT