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

Primary Purpose

Head and Neck Cancer

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
cisplatin
docetaxel
fluorouracil
radiation therapy
Sponsored by
European Organisation for Research and Treatment of Cancer - EORTC
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Head and Neck Cancer focused on measuring stage III squamous cell carcinoma of the lip and oral cavity, stage IV squamous cell carcinoma of the lip and oral cavity, stage III squamous cell carcinoma of the oropharynx, stage IV squamous cell carcinoma of the oropharynx, stage III squamous cell carcinoma of the hypopharynx, stage IV squamous cell carcinoma of the hypopharynx, stage III squamous cell carcinoma of the larynx, stage IV squamous cell carcinoma of the larynx

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Landeskrankenhaus/Universitatskliniken Graz
  • Allgemeines Krankenhaus der Stadt Wien
  • Kaiser Franz Josef Hospital
  • Algemeen Ziekenhuis Middelheim
  • Institut Jules Bordet
  • Universitair Ziekenhuis Antwerpen
  • Centre Hospitalier Regional de la Citadelle
  • Clinique Universitaire De Mont-Godinne
  • Institute of Oncology and Radiology of Serbia
  • CHR de Besancon - Hopital Jean Minjoz
  • Centre Oscar Lambret
  • Centre Hospital Regional Universitaire de Limoges
  • Centre Leon Berard
  • CRLCC Nantes - Atlantique
  • CHR Hotel Dieu
  • Centre Antoine Lacassagne
  • Martin Luther Universitaet
  • Caritasklinik St. Theresia
  • Mutterhaus der Borromaerinnen
  • Ahepa University Hospital
  • National Institute of Oncology
  • Szent Margit Hospital
  • Borsod-Abauj-Zemplen County Hospital
  • Centro di Riferimento Oncologico - Aviano
  • Ospedale Santa Croce
  • Istituti Fisioterapici Ospitalieri - Roma
  • Ospedale di Circolo e Fondazione Macchi
  • Academisch Medisch Centrum
  • Leiden University Medical Center
  • Academisch Ziekenhuis Maastricht
  • University Medical Center Nijmegen
  • Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology
  • National Cancer Institute - Bratislava
  • Institut Catala d'Oncologia - Hospital Duran i Reynals
  • Hospital General de Jerez
  • Universidad de Santiago - Hospital de Conxo
  • Hospital Clinico Universitario de Valencia
  • Kantonspital Aarau
  • Ospedale San Giovanni
  • Istanbul University-Institute of Oncology
  • Charing Cross Hospital
  • Middlesex Hospital- Meyerstein Institute
  • Newcastle General Hospital
  • Beatson Oncology Centre

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 1, 1999
Last Updated
July 6, 2018
Sponsor
European Organisation for Research and Treatment of Cancer - EORTC
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1. Study Identification

Unique Protocol Identification Number
NCT00003888
Brief Title
Combination Chemotherapy Plus Radiation Therapy in Treating Patients With Advanced Head and Neck Cancer
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 Type
Interventional

2. Study Status

Record Verification Date
July 2015
Overall Recruitment Status
Completed
Study Start Date
April 1999 (undefined)
Primary Completion Date
March 2002 (Actual)
Study Completion Date
March 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
European Organisation for Research and Treatment of Cancer - EORTC

4. Oversight

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Head and Neck Cancer
Keywords
stage III squamous cell carcinoma of the lip and oral cavity, stage IV squamous cell carcinoma of the lip and oral cavity, stage III squamous cell carcinoma of the oropharynx, stage IV squamous cell carcinoma of the oropharynx, stage III squamous cell carcinoma of the hypopharynx, stage IV squamous cell carcinoma of the hypopharynx, stage III squamous cell carcinoma of the larynx, stage IV squamous cell carcinoma of the larynx

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Allocation
Randomized
Enrollment
359 (Actual)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
cisplatin
Intervention Type
Drug
Intervention Name(s)
docetaxel
Intervention Type
Drug
Intervention Name(s)
fluorouracil
Intervention Type
Radiation
Intervention Name(s)
radiation therapy

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jan B. Vermorken, MD, PhD
Organizational Affiliation
University Hospital, Antwerp
Official's Role
Study Chair
Facility Information:
Facility Name
Landeskrankenhaus/Universitatskliniken Graz
City
Graz
ZIP/Postal Code
A-8036
Country
Austria
Facility Name
Allgemeines Krankenhaus der Stadt Wien
City
Vienna
ZIP/Postal Code
A-1090
Country
Austria
Facility Name
Kaiser Franz Josef Hospital
City
Vienna
ZIP/Postal Code
A-1100
Country
Austria
Facility Name
Algemeen Ziekenhuis Middelheim
City
Antwerp
ZIP/Postal Code
2020
Country
Belgium
Facility Name
Institut Jules Bordet
City
Brussels
ZIP/Postal Code
1000
Country
Belgium
Facility Name
Universitair Ziekenhuis Antwerpen
City
Edegem
ZIP/Postal Code
B-2650
Country
Belgium
Facility Name
Centre Hospitalier Regional de la Citadelle
City
Liege
ZIP/Postal Code
4000
Country
Belgium
Facility Name
Clinique Universitaire De Mont-Godinne
City
Mont-Godinne Yvoir
ZIP/Postal Code
5530
Country
Belgium
Facility Name
Institute of Oncology and Radiology of Serbia
City
Belgrade
ZIP/Postal Code
11000
Country
Former Yugoslavia
Facility Name
CHR de Besancon - Hopital Jean Minjoz
City
Besancon
ZIP/Postal Code
25030
Country
France
Facility Name
Centre Oscar Lambret
City
Lille
ZIP/Postal Code
59020
Country
France
Facility Name
Centre Hospital Regional Universitaire de Limoges
City
Limoges
ZIP/Postal Code
87042
Country
France
Facility Name
Centre Leon Berard
City
Lyon
ZIP/Postal Code
69373
Country
France
Facility Name
CRLCC Nantes - Atlantique
City
Nantes-Saint Herblain
ZIP/Postal Code
44805
Country
France
Facility Name
CHR Hotel Dieu
City
Nantes
ZIP/Postal Code
44093
Country
France
Facility Name
Centre Antoine Lacassagne
City
Nice
ZIP/Postal Code
06189
Country
France
Facility Name
Martin Luther Universitaet
City
Halle
ZIP/Postal Code
DOH-0-6112
Country
Germany
Facility Name
Caritasklinik St. Theresia
City
Saarbrucken
ZIP/Postal Code
D-66113
Country
Germany
Facility Name
Mutterhaus der Borromaerinnen
City
Trier
ZIP/Postal Code
D-54219
Country
Germany
Facility Name
Ahepa University Hospital
City
Thessaloniki
ZIP/Postal Code
54636
Country
Greece
Facility Name
National Institute of Oncology
City
Budapest
ZIP/Postal Code
1125
Country
Hungary
Facility Name
Szent Margit Hospital
City
Budapest
ZIP/Postal Code
3761
Country
Hungary
Facility Name
Borsod-Abauj-Zemplen County Hospital
City
Miskolc
ZIP/Postal Code
3501
Country
Hungary
Facility Name
Centro di Riferimento Oncologico - Aviano
City
Aviano
ZIP/Postal Code
33081
Country
Italy
Facility Name
Ospedale Santa Croce
City
Cuneo
ZIP/Postal Code
12100
Country
Italy
Facility Name
Istituti Fisioterapici Ospitalieri - Roma
City
Rome
ZIP/Postal Code
00161
Country
Italy
Facility Name
Ospedale di Circolo e Fondazione Macchi
City
Varese
ZIP/Postal Code
21100
Country
Italy
Facility Name
Academisch Medisch Centrum
City
Amsterdam
ZIP/Postal Code
1105 AZ
Country
Netherlands
Facility Name
Leiden University Medical Center
City
Leiden
ZIP/Postal Code
2300 CA
Country
Netherlands
Facility Name
Academisch Ziekenhuis Maastricht
City
Maastricht
ZIP/Postal Code
6202 AZ
Country
Netherlands
Facility Name
University Medical Center Nijmegen
City
Nijmegen
ZIP/Postal Code
NL-6500 HB
Country
Netherlands
Facility Name
Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology
City
Warsaw
ZIP/Postal Code
02-781
Country
Poland
Facility Name
National Cancer Institute - Bratislava
City
Bratislava
ZIP/Postal Code
833 10
Country
Slovakia
Facility Name
Institut Catala d'Oncologia - Hospital Duran i Reynals
City
Barcelona
ZIP/Postal Code
08907
Country
Spain
Facility Name
Hospital General de Jerez
City
Jerez
ZIP/Postal Code
11407
Country
Spain
Facility Name
Universidad de Santiago - Hospital de Conxo
City
Santiago de Compostela
Country
Spain
Facility Name
Hospital Clinico Universitario de Valencia
City
Valencia
ZIP/Postal Code
46010
Country
Spain
Facility Name
Kantonspital Aarau
City
Aarau
ZIP/Postal Code
5001
Country
Switzerland
Facility Name
Ospedale San Giovanni
City
Bellinzona
ZIP/Postal Code
CH-6500
Country
Switzerland
Facility Name
Istanbul University-Institute of Oncology
City
Istanbul
ZIP/Postal Code
34390
Country
Turkey
Facility Name
Charing Cross Hospital
City
London
State/Province
England
ZIP/Postal Code
W6 8RF
Country
United Kingdom
Facility Name
Middlesex Hospital- Meyerstein Institute
City
London
State/Province
England
ZIP/Postal Code
WIT 3AA
Country
United Kingdom
Facility Name
Newcastle General Hospital
City
Newcastle Upon Tyne
State/Province
England
ZIP/Postal Code
NE4 6BE
Country
United Kingdom
Facility Name
Beatson Oncology Centre
City
Glasgow
State/Province
Scotland
ZIP/Postal Code
G11 6NT
Country
United Kingdom

12. IPD Sharing Statement

Citations:
Citation
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.
Results Reference
background
PubMed Identifier
20842129
Citation
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.
Results Reference
result
PubMed Identifier
17960012
Citation
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.
Results Reference
result
Citation
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.
Results Reference
result
Citation
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.
Results Reference
result
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 III trial of the EORTC Head and Neck Cancer Group (EORTC #24971). [Abstract] J Clin Oncol 22 (Suppl 14): A-5508, 490s, 2004.
Results Reference
result

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

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