Back to resultsCetuximab (Erbitux) in Combination With Cisplatin or Carboplatin and 5-Fluorouracil in the First Line Treatment of Subjects With Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck (EXTREME)
Primary Purpose
Head and Neck Cancer
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Cetuximab + Platinum (Cisplatin or Carboplatin) + 5Fluorouracil (5-FU)
Platinum (Cisplatin or Carboplatin) + 5-FU
Sponsored by
About this trial
This is an interventional treatment trial for Head and Neck Cancer focused on measuring Head and Neck Cancer
Eligibility Criteria
Inclusion Criteria: Histologically or cytologically confirmed diagnosis of squamous cell carcinoma of the head and neck (SCCHN) Recurrent and/or metastatic SCCHN, not suitable for local therapy Exclusion Criteria: Prior systemic chemotherapy, except if given as part of a multimodal treatment for locally advanced disease which was completed more than 6 months prior to study entry Surgery (excluding prior diagnostic biopsy), or irradiation within 4 weeks before study entry Nasopharyngeal carcinoma
Sites / Locations
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Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Cetuximab Plus Chemotherapy
Chemotherapy alone
Arm Description
Outcomes
Primary Outcome Measures
Overall Survival Time (OS)
Time from randomization to death. Patients without event are censored at the last date known to be alive or at the clinical cut-off date, whatever is earlier.
Secondary Outcome Measures
Progression-free Survival Time (PFS)
Duration from randomization until radiological progression according to investigator (based on modified World Health Organisation (WHO) criteria) or death due to any cause.
Only deaths within 60 days of last tumor assessment are considered. Patients without event are censored on the date of last tumor assessment.
Best Overall Response
The best overall response rate is defined as the percentage of subjects having achieved confirmed Complete Response + Partial Response as the best overall response according to radiological assessments according to investigator (based on modified WHO criteria).
Disease Control
The disease control rate is defined as the percentage of subjects having achieved confirmed Complete Response + Partial Response + Stable Disease as best overall response according to radiological assessments according to investigator (based on modified WHO criteria).
Time to Treatment Failure
Time from randomization to date of the first occurrence of; progression, discontinuation of treatment due to progression or adverse event, start of new anticancer therapy, withdrawal of consent, or death (within 60 days of last tumor assessment).
Patients without event are censored on the date of last tumor assessment.
Duration of Response
Time from first assessment of Complete Response or Partial Response to disease progression or death (within 60 days of last tumor assessment).
Patients without event are censored on the date of last tumor assessment. Tumor assessments based on modified WHO criteria.
Quality of Life (QOL) Assessment European Organisation for the Research and Treatment of Cancer (EORTC) QLQ-C30 Global Health Status
Mean global health status scores (EORTC QLQ-C30) against time for each treatment group. Scores were derived from mutually exclusive sets of items, with scale scores ranging from 0 to 100 after a linear transformation. Higher scores indicate a better QoL.
Quality of Life Assessment (EORTC QLQ-C30) Social Functioning
Mean social functioning scores (EORTC QLQ-C30) against time for each treatment group. Scores were derived from mutually exclusive sets of items, with scale scores ranging from 0 to 100 after a linear transformation. Higher scores indicate a higher level of social functioning.
Safety - Number of Patients Experiencing Any Adverse Event
Please refer to Adverse Events section for further details
Full Information
NCT ID
NCT00122460
First Posted
July 19, 2005
Last Updated
July 11, 2014
Sponsor
Merck KGaA, Darmstadt, Germany
1. Study Identification
Unique Protocol Identification Number
NCT00122460
Brief Title
Cetuximab (Erbitux) in Combination With Cisplatin or Carboplatin and 5-Fluorouracil in the First Line Treatment of Subjects With Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck (EXTREME)
Official Title
Cetuximab in Combination With Cisplatin or Carboplatin and 5-Fluorouracil in the First Line Treatment of Subjects With Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck
Study Type
Interventional
2. Study Status
Record Verification Date
July 2014
Overall Recruitment Status
Completed
Study Start Date
December 2004 (undefined)
Primary Completion Date
March 2007 (Actual)
Study Completion Date
January 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck KGaA, Darmstadt, Germany
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this trial is to investigate the efficacy of cetuximab in combination with chemotherapy in comparison to chemotherapy alone in patients with recurrent or metastatic head and neck cancer. Overall survival will be taken as the primary measure of efficacy.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Head and Neck Cancer
Keywords
Head and Neck Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
442 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cetuximab Plus Chemotherapy
Arm Type
Experimental
Arm Title
Chemotherapy alone
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Cetuximab + Platinum (Cisplatin or Carboplatin) + 5Fluorouracil (5-FU)
Intervention Description
Subjects in will receive initial dose of 400 mg/m^2 cetuximab (over 2 hours) followed by weekly doses of 250 mg/m^2 (over 1 hour). All doses will be given by intravenous (IV) infusion. Subjects will receive either Cisplatin (100 mg/m^2 on day 1) + 5-FU (1000 mg/m^2 continuous IV from day 1 to day 4) every 3 weeks or Carboplatin (Area under the curve (AUC) 5 IV on day 1) + 5-FU (1000 mg/m^2 continuous IV from day 1 to day 4) every 3 weeks
Intervention Type
Drug
Intervention Name(s)
Platinum (Cisplatin or Carboplatin) + 5-FU
Intervention Description
All doses will be given by IV infusion. Subjects will receive either Cisplatin (100 mg/m^2 on day 1) + 5-FU (1000 mg/m^2 continuous IV from day 1 to day 4) every 3 weeks or Carboplatin (AUC 5 IV on day 1) + 5-FU (1000 mg/m^2 continuous IV from day 1 to day 4) every 3 weeks
Primary Outcome Measure Information:
Title
Overall Survival Time (OS)
Description
Time from randomization to death. Patients without event are censored at the last date known to be alive or at the clinical cut-off date, whatever is earlier.
Time Frame
time from randomization to death or last day known to be alive, reported between day of first patient randomised, 21 Dec 2004, until cut-off date 12 Mar 2007
Secondary Outcome Measure Information:
Title
Progression-free Survival Time (PFS)
Description
Duration from randomization until radiological progression according to investigator (based on modified World Health Organisation (WHO) criteria) or death due to any cause.
Only deaths within 60 days of last tumor assessment are considered. Patients without event are censored on the date of last tumor assessment.
Time Frame
time from randomization to disease progression, death or last tumor assessment, reported between day of first patient randomised, 21 Dec 2004, until cut-off date 12 Mar 2007
Title
Best Overall Response
Description
The best overall response rate is defined as the percentage of subjects having achieved confirmed Complete Response + Partial Response as the best overall response according to radiological assessments according to investigator (based on modified WHO criteria).
Time Frame
evaluations were performed every 6 weeks until progression, reported between day of first patient randomised, 21 Dec 2004, until cut-off date 12 Mar 2007
Title
Disease Control
Description
The disease control rate is defined as the percentage of subjects having achieved confirmed Complete Response + Partial Response + Stable Disease as best overall response according to radiological assessments according to investigator (based on modified WHO criteria).
Time Frame
evaluations were performed every 6 weeks until progression, reported between day of first patient randomised, 21 Dec 2004, until cut-off date 12 Mar 2007
Title
Time to Treatment Failure
Description
Time from randomization to date of the first occurrence of; progression, discontinuation of treatment due to progression or adverse event, start of new anticancer therapy, withdrawal of consent, or death (within 60 days of last tumor assessment).
Patients without event are censored on the date of last tumor assessment.
Time Frame
Time from randomization to treatment failure or last tumor assessment, reported between day of first patient randomised, 21 Dec 2004, until cut-off date 12 Mar 2007
Title
Duration of Response
Description
Time from first assessment of Complete Response or Partial Response to disease progression or death (within 60 days of last tumor assessment).
Patients without event are censored on the date of last tumor assessment. Tumor assessments based on modified WHO criteria.
Time Frame
time from first assessment of Complete Response or Partial Response to disease progression, death or last tumor assessment, reported between day of first patient randomised, 21 Dec 2004, until cut-off date 12 Mar 2007
Title
Quality of Life (QOL) Assessment European Organisation for the Research and Treatment of Cancer (EORTC) QLQ-C30 Global Health Status
Description
Mean global health status scores (EORTC QLQ-C30) against time for each treatment group. Scores were derived from mutually exclusive sets of items, with scale scores ranging from 0 to 100 after a linear transformation. Higher scores indicate a better QoL.
Time Frame
at baseline, day 1 of cycle 3, first 6-weekly evaluation following completion of chemotherapy, 6 & 12 months after randomization, reported between day of first patient randomised, 21 Dec 2004,until cut-off date, 12 Mar 2007
Title
Quality of Life Assessment (EORTC QLQ-C30) Social Functioning
Description
Mean social functioning scores (EORTC QLQ-C30) against time for each treatment group. Scores were derived from mutually exclusive sets of items, with scale scores ranging from 0 to 100 after a linear transformation. Higher scores indicate a higher level of social functioning.
Time Frame
at baseline, day 1 of cycle 3, first 6-weekly evaluation following completion of chemotherapy, 6 & 12 months after randomization, reported between day of first patient randomised, 21 Dec 2004,until cut-off date, 12 Mar 2007
Title
Safety - Number of Patients Experiencing Any Adverse Event
Description
Please refer to Adverse Events section for further details
Time Frame
time from first dose up to 30 after last dose of study treatment, reported between day of first dose of study treatment, 22 Dec 2004, until cut-off date 12 Mar 2007
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically or cytologically confirmed diagnosis of squamous cell carcinoma of the head and neck (SCCHN)
Recurrent and/or metastatic SCCHN, not suitable for local therapy
Exclusion Criteria:
Prior systemic chemotherapy, except if given as part of a multimodal treatment for locally advanced disease which was completed more than 6 months prior to study entry
Surgery (excluding prior diagnostic biopsy), or irradiation within 4 weeks before study entry
Nasopharyngeal carcinoma
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Responsible
Organizational Affiliation
Merck KGaA, Darmstadt, Germany
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Innsbruck
Country
Austria
Facility Name
Research Site
City
Wien
Country
Austria
Facility Name
Research Site
City
Bruxelles
Country
Belgium
Facility Name
Research Site
City
Edegem
Country
Belgium
Facility Name
Research Site
City
Gent
Country
Belgium
Facility Name
Research Site
City
Ceske Budejovice
Country
Czech Republic
Facility Name
Research Site
City
Prague
Country
Czech Republic
Facility Name
Research Site
City
Caen
Country
France
Facility Name
Research Site
City
Dijon
Country
France
Facility Name
Research Site
City
Lille
Country
France
Facility Name
Research Site
City
Limoges
Country
France
Facility Name
Research Site
City
Marseille
Country
France
Facility Name
Research Site
City
Montpellier
Country
France
Facility Name
Research Site
City
Nantes-Saint Herblain
Country
France
Facility Name
Research Site
City
Nice
Country
France
Facility Name
Research Site
City
Strasbourg
Country
France
Facility Name
Research Site
City
Toulouse
Country
France
Facility Name
Research Site
City
Tours
Country
France
Facility Name
Research Site
City
Vandoeuvre les Nancy
Country
France
Facility Name
Research Site
City
Berlin
Country
Germany
Facility Name
Research Site
City
Essen
Country
Germany
Facility Name
Research Site
City
Frankfurt on the Main
Country
Germany
Facility Name
Research Site
City
Hamburg
Country
Germany
Facility Name
Research Site
City
Munich
Country
Germany
Facility Name
Research Site
City
Oldenburg
Country
Germany
Facility Name
Research Site
City
Stuttgart
Country
Germany
Facility Name
Research Site
City
Budapest
Country
Hungary
Facility Name
Research Site
City
Gyor
Country
Hungary
Facility Name
Research Site
City
Kecskemet
Country
Hungary
Facility Name
Research Site
City
Nyiregyhaza
Country
Hungary
Facility Name
Research Site
City
Cuneo
Country
Italy
Facility Name
Research Site
City
Genoa
Country
Italy
Facility Name
Research Site
City
Milan
Country
Italy
Facility Name
Research Site
City
Monserrato
Country
Italy
Facility Name
Research Site
City
Naples
Country
Italy
Facility Name
Research Site
City
Rome
Country
Italy
Facility Name
Research Site
City
Amsterdam
Country
Netherlands
Facility Name
Research Site
City
Nijmegen
Country
Netherlands
Facility Name
Research Site
City
Gdansk
Country
Poland
Facility Name
Research Site
City
Krakow
Country
Poland
Facility Name
Research Site
City
Warszawa
Country
Poland
Facility Name
Research Site
City
Lisbon
Country
Portugal
Facility Name
Research Site
City
Porto
Country
Portugal
Facility Name
Research Site
City
Moscow
Country
Russian Federation
Facility Name
Research Site
City
St. Petersburg
Country
Russian Federation
Facility Name
Research Site
City
Bratislava
Country
Slovakia
Facility Name
Research Site
City
Kosice
Country
Slovakia
Facility Name
Research Site
City
Barcelona
Country
Spain
Facility Name
Research Site
City
L'Hospitalet de Llobregat
Country
Spain
Facility Name
Research Site
City
Madrid
Country
Spain
Facility Name
Research Site
City
Malaga
Country
Spain
Facility Name
Research Site
City
San Sebastian
Country
Spain
Facility Name
Research Site
City
Santander
Country
Spain
Facility Name
Research Site
City
Sevilla
Country
Spain
Facility Name
Research Site
City
Valencia
Country
Spain
Facility Name
Research Site
City
Lind
Country
Sweden
Facility Name
Research Site
City
Umea
Country
Sweden
Facility Name
Research Site
City
Örebo
Country
Sweden
Facility Name
Research Site
City
Geneva
Country
Switzerland
Facility Name
Research Site
City
Thun
Country
Switzerland
Facility Name
Research Site
City
Zürich
Country
Switzerland
Facility Name
Research Site
City
Donetsk
Country
Ukraine
Facility Name
Research Site
City
Kharkiv
Country
Ukraine
Facility Name
Research Site
City
Kiev
Country
Ukraine
Facility Name
Research Site
City
Sumy
Country
Ukraine
Facility Name
Research Site
City
Chelmsford
Country
United Kingdom
Facility Name
Research Site
City
Edinburgh
Country
United Kingdom
Facility Name
Research Site
City
London
Country
United Kingdom
Facility Name
Research Site
City
Manchester
Country
United Kingdom
Facility Name
Research Site
City
Nottingham
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
18784101
Citation
Vermorken JB, Mesia R, Rivera F, Remenar E, Kawecki A, Rottey S, Erfan J, Zabolotnyy D, Kienzer HR, Cupissol D, Peyrade F, Benasso M, Vynnychenko I, De Raucourt D, Bokemeyer C, Schueler A, Amellal N, Hitt R. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med. 2008 Sep 11;359(11):1116-27. doi: 10.1056/NEJMoa0802656.
Results Reference
result
PubMed Identifier
20335368
Citation
Mesia R, Rivera F, Kawecki A, Rottey S, Hitt R, Kienzer H, Cupissol D, De Raucourt D, Benasso M, Koralewski P, Delord JP, Bokemeyer C, Curran D, Gross A, Vermorken JB. Quality of life of patients receiving platinum-based chemotherapy plus cetuximab first line for recurrent and/or metastatic squamous cell carcinoma of the head and neck. Ann Oncol. 2010 Oct;21(10):1967-1973. doi: 10.1093/annonc/mdq077. Epub 2010 Mar 24.
Results Reference
result
PubMed Identifier
32993574
Citation
Hecht M, Hahn D, Wolber P, Hautmann MG, Reichert D, Weniger S, Belka C, Bergmann T, Gohler T, Welslau M, Grosse-Thie C, Guntinas-Lichius O, von der Grun J, Balermpas P, Orlowski K, Messinger D, Stenzel KG, Fietkau R. Treatment response lowers tumor symptom burden in recurrent and/or metastatic head and neck cancer. BMC Cancer. 2020 Sep 29;20(1):933. doi: 10.1186/s12885-020-07440-w.
Results Reference
derived
PubMed Identifier
23265711
Citation
Licitra L, Storkel S, Kerr KM, Van Cutsem E, Pirker R, Hirsch FR, Vermorken JB, von Heydebreck A, Esser R, Celik I, Ciardiello F. Predictive value of epidermal growth factor receptor expression for first-line chemotherapy plus cetuximab in patients with head and neck and colorectal cancer: analysis of data from the EXTREME and CRYSTAL studies. Eur J Cancer. 2013 Apr;49(6):1161-8. doi: 10.1016/j.ejca.2012.11.018. Epub 2012 Dec 19.
Results Reference
derived
Learn more about this trial
Cetuximab (Erbitux) in Combination With Cisplatin or Carboplatin and 5-Fluorouracil in the First Line Treatment of Subjects With Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck (EXTREME)
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