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)

• ClinicalTrials.gov Identifier: NCT00122460
• Recruitment Status: Completed
• First Posted: July 22, 2005
• Results First Posted: September 30, 2011
• Last Update Posted: July 23, 2014
• Sponsor: Merck KGaA, Darmstadt, Germany
• Information provided by (Responsible Party): Merck KGaA, Darmstadt, Germany

Tracking Information

• First Submitted Date: July 19, 2005
• First Posted Date: July 22, 2005
• Results First Submitted Date: August 25, 2011
• Results First Posted Date: September 30, 2011
• Last Update Posted Date: July 23, 2014
• Study Start Date: December 2004
• Actual Primary Completion Date: March 2007 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 25, 2011)

Overall Survival Time (OS) [ 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 ]

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.

• Original Primary Outcome Measures: Not Provided

Current Secondary Outcome Measures (submitted: August 25, 2011)

• Progression-free Survival Time (PFS) [ 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 ]
  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 [ 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 ]
  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 [ 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 ]
  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 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 ]
  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 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 ]
  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 [ 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 ]
  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 [ 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 ]
  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 [ 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 ]
  Please refer to Adverse Events section for further details

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Head and Neck Cancer

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
• Drug: 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

Study Arms

• Experimental: Cetuximab Plus Chemotherapy
  Intervention: Drug: Cetuximab + Platinum (Cisplatin or Carboplatin) + 5Fluorouracil (5-FU)
• Active Comparator: Chemotherapy alone
  Intervention: Drug: Platinum (Cisplatin or Carboplatin) + 5-FU

Publications *

• 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.
• 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.
• 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.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 13, 2007): 442
• Original Enrollment (submitted: July 19, 2005): 420
• Actual Study Completion Date: January 2011
• Actual Primary Completion Date: March 2007 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Austria, Belgium, Czech Republic, France, Germany, Hungary, Italy, Netherlands, Poland, Portugal, Russian Federation, Slovakia, Spain, Sweden, Switzerland, Ukraine, United Kingdom

Administrative Information

• NCT Number: NCT00122460
• Other Study ID Numbers: EMR 62202-002
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Merck KGaA, Darmstadt, Germany
• Original Responsible Party: Not Provided
• Current Study Sponsor: Merck KGaA, Darmstadt, Germany
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Medical Responsible; Merck KGaA, Darmstadt, Germany

• PRS Account: Merck KGaA, Darmstadt, Germany
• Verification Date: July 2014