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)

Head and Neck Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00122460
• Other study ID #: EMR 62202-002
• Status: Completed
• Phase: Phase 3
• First received: July 19, 2005
• Last updated: July 11, 2014
• Start date: December 2004
• Est. completion date: January 2011

Study information

• Verified date: July 2014
• Source: Merck KGaA
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicines and Health Products, FAMHP
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 442
• Est. completion date: January 2011
• Est. primary completion date: March 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

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

Intervention

Drug:
• Cetuximab + Platinum (Cisplatin or Carboplatin) + 5Fluorouracil (5-FU)
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
• Platinum (Cisplatin or Carboplatin) + 5-FU
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

Locations

Country	Name	City	State
Austria	Research Site	Innsbruck
Austria	Research Site	Wien
Belgium	Research Site	Bruxelles
Belgium	Research Site	Edegem
Belgium	Research Site	Gent
Czech Republic	Research Site	Ceske Budejovice
Czech Republic	Research Site	Prague
France	Research Site	Caen
France	Research Site	Dijon
France	Research Site	Lille
France	Research Site	Limoges
France	Research Site	Marseille
France	Research Site	Montpellier
France	Research Site	Nantes-Saint Herblain
France	Research Site	Nice
France	Research Site	Strasbourg
France	Research Site	Toulouse
France	Research Site	Tours
France	Research Site	Vandoeuvre les Nancy
Germany	Research Site	Berlin
Germany	Research Site	Essen
Germany	Research Site	Frankfurt on the Main
Germany	Research Site	Hamburg
Germany	Research Site	Munich
Germany	Research Site	Oldenburg
Germany	Research Site	Stuttgart
Hungary	Research Site	Budapest
Hungary	Research Site	Gyor
Hungary	Research Site	Kecskemet
Hungary	Research Site	Nyiregyhaza
Italy	Research Site	Cuneo
Italy	Research Site	Genoa
Italy	Research Site	Milan
Italy	Research Site	Monserrato
Italy	Research Site	Naples
Italy	Research Site	Rome
Netherlands	Research Site	Amsterdam
Netherlands	Research Site	Nijmegen
Poland	Research Site	Gdansk
Poland	Research Site	Krakow
Poland	Research Site	Warszawa
Portugal	Research Site	Lisbon
Portugal	Research Site	Porto
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	St. Petersburg
Slovakia	Research Site	Bratislava
Slovakia	Research Site	Kosice
Spain	Research Site	Barcelona
Spain	Research Site	L'Hospitalet de Llobregat
Spain	Research Site	Madrid
Spain	Research Site	Malaga
Spain	Research Site	San Sebastian
Spain	Research Site	Santander
Spain	Research Site	Sevilla
Spain	Research Site	Valencia
Sweden	Research Site	Lind
Sweden	Research Site	Örebo
Sweden	Research Site	Umea
Switzerland	Research Site	Geneva
Switzerland	Research Site	Thun
Switzerland	Research Site	Zürich
Ukraine	Research Site	Donetsk
Ukraine	Research Site	Kharkiv
Ukraine	Research Site	Kiev
Ukraine	Research Site	Sumy
United Kingdom	Research Site	Chelmsford
United Kingdom	Research Site	Edinburgh
United Kingdom	Research Site	London
United Kingdom	Research Site	Manchester
United Kingdom	Research Site	Nottingham

Sponsors (1)

Lead Sponsor	Collaborator
Merck KGaA

Countries where clinical trial is conducted

Austria,  Belgium,  Czech Republic,  France,  Germany,  Hungary,  Italy,  Netherlands,  Poland,  Portugal,  Russian Federation,  Slovakia,  Spain,  Sweden,  Switzerland,  Ukraine,  United Kingdom, 

References & Publications (2)

Mesía 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 — View 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 h — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	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	No
Secondary	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.	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	No
Secondary	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).	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	No
Secondary	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).	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	No
Secondary	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.	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	No
Secondary	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.	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	No
Secondary	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.	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	No
Secondary	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.	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	No
Secondary	Safety - Number of Patients Experiencing Any Adverse Event	Please refer to Adverse Events section for further details	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	Yes