Drugs used against cancer work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Giving combination chemotherapy together with cetuximab as first treatment after diagnosis of a metastatic colorectal cancer ('1st-line' treatment) may improve the treatment efficacy. However, it is not yet known whether giving combination chemotherapy together with cetuximab is more effective than combination chemotherapy alone. This open-label trial investigates the effectiveness of cetuximab in combination with a standard and effective chemotherapy (5-Fluorouracil (5FU)/Folinic acid (FA) plus irinotecan) for metastatic colorectal cancer in first-line setting, compared to the same chemotherapy alone on patient expressing the epidermal growth factor (EGF) receptor. Patients expressing this EGF Receptor will be randomly assign in one of the 2 groups to either receive the combination chemotherapy alone or with cetuximab (open-label study) and will then be treated until progression of the disease or unacceptable toxicity occur. Regular efficacy assessments (every 8 weeks) based on imaging will be performed throughout the study together with regular safety assessments (e.g. safety labs). An independent Safety Board of experts will also monitor safety data. After participant discontinuation from the trial, regular updates on further treatments and survival status will be requested from the investigator. The entire study (from the first patient entering the study to the last collect of follow-up information) is 4-5 years long.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
1,221
Cetuximab intravenous infusion of 400mg/m\^2 for the first infusion then weekly intravenous infusion of 250mg/m\^2. Number of Cycles: until progression or unacceptable toxicity develops
Bi-weekly Irinotecan infusion of 180mg/m\^2, Folinic Acid infusion of 400mg/m\^2 (racemic) or 200mg/m\^2 (L-form), 5-Fluorouracil bolus of 400mg/m\^2 followed by a 46-hour continuous infusion of 2400mg/m\^2 Number of Cycles: until progression or unacceptable toxicity develops
Research Site
Buenos Aires, Argentina
Research Site
Bedford Park, Australia
Research Site
Darlinghurst, Australia
Research Site
Heidelberg, Australia
Research Site
Nedlands, Australia
Research Site
West Perth, Australia
Progression-free Survival (PFS) Time - Independent Review Committee (IRC) Assessments
Duration from randomization until radiological progression (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 randomisation to disease progression, death or last tumour assessment, reported between day of first patient randomised, 10 Aug 2004, until cut-off date, 27 July 2006
Progression-free Survival Time (Chinese V-Ki-ras2 Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) Wild-Type Population) - Independent Review Committee (IRC) Assessments
Duration from randomization until radiological progression (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 frame: Time from randomisation to disease progression, death or last tumour assessment, reported between day of first patient randomised, 10 Aug 2004, until cut-off date, 27 July 2006
Progression-free Survival Time (KRAS Mutant Population) - Independent Review Committee (IRC) Assessments
Duration from randomization until radiological progression (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 frame: Time from randomisation to disease progression, death or last tumour assessment, reported between day of first patient randomised, 10 Aug 2004, until cut-off date, 27 July 2006
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, whichever is later.
Time frame: Time from randomisation to death or last day known to be alive, reported between day of first patient randomised, 10 Aug 2004, until cut-off date, 31 May 2009
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, whichever is later.
Time frame: Time from randomisation to death or last day known to be alive reported between day of first patient randomised, 10 Aug 2004, until cut-off date, 31 May 2009
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, whichever is later.
Time frame: Time from randomisation to death or last day known to be alive reported between day of first patient randomised, 10 Aug 2004, until cut-off date, 31 May 2009
Best Overall Response Rate - Independent Review Committee (IRC) Assessments
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).
Time frame: evaluations were performed every 6 weeks until progression reported between day of first patient randomised, 10 Aug 2004, until cut-off date, 27 July 2006
Best Overall Response Rate (KRAS Wild-Type Population) - Independent Review Committee (IRC) Assessments
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).
Time frame: evaluations were performed every 6 weeks until progression reported between day of first patient randomised, 10 Aug 2004, until cut-off date, 27 July 2006
Best Overall Response Rate (KRAS Mutant Population) - Independent Review Committee (IRC) Assessments
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).
Time frame: evaluations were performed every 6 weeks until progression reported between day of first patient randomised, 10 Aug 2004, until cut-off date, 27 July 2006
Disease Control Rate - Independent Review Committee (IRC) Assessments
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 (based on modified WHO criteria).
Time frame: Evaluations were performed every 6 weeks until progression reported between day of first patient randomised, 10 Aug 2004, until cut-off date, 27 July 2006
Duration of Response - Independent Review Committee (IRC) Assessments
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, 10 Aug 2004, until cut-off date, 27 July 2006
Participants With No Residual Tumor After Metastatic Surgery
Participants with no residual tumor after on-study surgery for metastases
Time frame: time from first dose up to 30 days after last dose of study treatment reported between day of first patient randomised, 10 Aug 2004, until cut-off date, 30 Nov 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.
Time frame: at baseline, at week 8, at week 16, at week 24, at week 32, and at week 40, reported between day of first patient randomised, 10 Aug 2004, until cut-off date, 27 July 2006
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 functioning.
Time frame: at baseline, at week 8, at week 16, at week 24, at week 32, and at week 40, reported between day of first patient randomised, 10 Aug 2004, until cut-off date, 27 July 2006
Safety - Number of Patients Experiencing Any Adverse Event
Please refer to Adverse Events section for further details
Time frame: time from first dose up to 30 days after last dose of study treatment reported between day of first patient randomised, 10 Aug 2004, until cut-off date, 30 Nov 2007
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