Oxaliplatin and Cetuximab in First-line Treatment of Metastatic Colorectal Cancer (mCRC)

Study Overview
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Brief Summary
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This is an open label, randomized, controlled, multicenter phase II study comparing 5-FU/FA + oxaliplatin (FOLFOX-4) + cetuximab versus 5-FU/FA + oxaliplatin as first-line treatment for epidermal growth factor receptor (EGFR)-expressing mCRC.

Official Title
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Open, Randomized, Controlled, Multicenter Phase II Study Comparing 5-FU/FA Plus Oxaliplatin (FOLFOX-4) Plus Cetuximab Versus 5-FU/FA Plus Oxaliplatin (FOLFOX-4) as First-line Treatment for Epidermal Growth Factor Receptor-expressing Metastatic Colorectal Cancer

Conditions
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Neoplasm Metastasis, Colorectal Cancer

Intervention / Treatment
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* Biological: Cetuximab
* Drug: Oxaliplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: First-line mCRC EGFR positive Bi-dimensional measurable index lesion Exclusion Criteria: Previous exposure to EGFR-targeting therapy Previous oxaliplatin-based therapy Previous chemotherapy for colorectal cancer except adjuvant treatment with progression of disease documented > 6 months after end of adjuvant treatment Radiotherapy Surgery Any other investigational drug in the 30 days before randomization Brain metastasis and/or leptomeningeal disease Acute or sub-acute intestinal occlusion or history of inflammatory bowel disease

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 FOLFOX-4<br> | Biological: Cetuximab<br>* Cetuximab will always be administered first, followed by oxaliplatin at least 1 hour later. Following completion of the oxaliplatin infusion or simultaneously with oxaliplatin folinic acid (FA) will be administered (at a dose of 200 mg/m^2, infused over 120 minutes, on day 1 and day 2, every two weeks) and then 5-Fluorouracil (5-FU) (as a bolus of 400 mg/m^2/day intravenously (IV) over 2-4 minutes followed by 600 mg/m^2/day infused over 22-hour, on day 1 and day 2, every two weeks). Until progression or unacceptable toxicity develops<br>|
| Active Comparator: FOLFOX-4 Alone<br> | Drug: Oxaliplatin<br>* Oxaliplatin will always be administered first or simultaneously with FA (at a dose of 200 mg/m^2, infused over 120 minutes, on day 1 and day 2, every two weeks) and then 5-FU (as a bolus of 400 mg/m^2/day IV over 2-4 minutes followed by 600 mg/m^2/day infused over 22-hour, on day 1 and day 2, every two weeks). Until progression or unacceptable toxicity develops<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Overall Response Rate - Independent Review Committee (IRC) | 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 (based on modified World Health Organisation (WHO) criteria) as assessed by an IRC. | Evaluations were performed every 6 weeks until progression, reported between day of first patient randomised, 27 Jul 2005, until cut-off date 4 August 2006 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Overall Response Rate (Chinese V-Ki-ras2 Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) Wild-Type Population) | 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 (based on modified WHO criteria) as assessed by an IRC. | Evaluations were performed every 6 weeks until progression, reported between day of first patient randomised, 27 Jul 2005, until cut-off date 1 Mar 2007 | 
| Best Overall Response Rate (KRAS Mutant Population) | 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 (based on modified WHO criteria) as assessed by an IRC. | Evaluations were performed every 6 weeks until progression, reported between day of first patient randomised, 27 Jul 2005, until cut-off date 1 Mar 2007 | 
| Progression-free Survival Time | Duration from randomization until radiological progression as assessed by an IRC (based on modified 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 randomisation to disease progression, death or last tumour assessment, reported between day of first patient randomised, 27 Jul 2005, until cut-off date 01 Mar 2007 | 
| Progression-free Survival Time (KRAS Wild-Type Population) | Duration from randomization until radiological progression as assessed by an IRC (based on modified 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 randomisation to disease progression, death or last tumour assessment, reported between day of first patient randomised, 27 Jul 2005, until cut-off date 30 Nov 2008 | 
| Progression-free Survival Time (KRAS Mutant Population) | Duration from randomization until radiological progression as assessed by an IRC (based on modified 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 randomisation to disease progression, death or last tumour assessment, reported between day of first patient randomised, 27 Jul 2005, until cut-off date 30 Nov 2008 | 
| Overall Survival Time | 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 randomisation to death or last day known to be alive, reported between day of first patient randomised, 27 Jul 2005, until cut-off date 30 Nov 2008 | 
| Overall Survival Time (KRAS Wild-Type Population) | 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 randomisation to death or last day known to be alive, reported between day of first patient randomised, 27 Jul 2005, until cut-off date 30 November 2008 | 
| Overall Survival Time (KRAS Mutant Population) | 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 randomisation to death or last day known to be alive, reported between day of first patient randomised, 27 Jul 2005, until cut-off date 30 November 2008 | 
| Participants With No Residual Tumor After Metastatic Surgery | No residual tumor after on-study surgery for metastases. | Time from first dose up to 30 days after the last dose of study treatment, reported between day of first patient randomised, 27 Jul 2005, until cut-off date 30 November 2008 | 
| Disease Control Rate (Cut Off Date 4 August 2006) | 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 as assessed by IRC (based on modified WHO criteria). | Evaluations were performed every 6 weeks until progression, reported between day of first patient randomised, 27 Jul 2005, until cut-off date 4 August 2006 | 
| 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, 27 Jul 2005, until cut-off date 01 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 patient dose of study treatment, 27 Jul 2005, until cut-off date 30 Nov 2008 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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metastatic CRC, FOLFOX-4, Cetuximab, First-line mCRC, EGFR positive