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)

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Head and Neck Cancer

Intervention / Treatment
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* Drug: Cetuximab + Platinum (Cisplatin or Carboplatin) + 5Fluorouracil (5-FU)
* Drug: Platinum (Cisplatin or Carboplatin) + 5-FU


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cetuximab Plus Chemotherapy<br> | Drug: Cetuximab + Platinum (Cisplatin or Carboplatin) + 5Fluorouracil (5-FU)<br>* 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<br>|
| Active Comparator: Chemotherapy alone<br> | Drug: Platinum (Cisplatin or Carboplatin) + 5-FU<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Head and Neck Cancer