Epidermal Growth Factor Receptor (EGFR) Expressing Metastatic Colorectal Cancer
Conditions
Keywords
Metastatic colorectal cancer, EGFR, Irinotecan, cetuximab, first-line treatment
Brief summary
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.
Interventions
DRUGCetuximab
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
Sponsors
Merck KGaA, Darmstadt, Germany
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of histologically confirmed adenocarcinoma of the colon or rectum * Inoperable metastatic disease * Immunohistochemical evidence of epidermal growth factor receptor expression in tumor tissue * Presence of at least 1 bi-dimensionally measurable index lesion
Exclusion criteria
* Previous irinotecan-based chemotherapy * Previous chemotherapy for colorectal cancer except adjuvant treatment if terminated more than 6 months before the start of study treatment * Radiotherapy, surgery (excluding prior diagnostic biopsy) or any investigational drug in the 30 days before the start of study treatment * Brain metastasis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) Time - Independent Review Committee (IRC) Assessments | 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 | 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. |
| Progression-free Survival Time (Chinese V-Ki-ras2 Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) Wild-Type Population) - Independent Review Committee (IRC) Assessments | 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 | 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. |
| Progression-free Survival Time (KRAS Mutant Population) - Independent Review Committee (IRC) Assessments | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Best Overall Response Rate - Independent Review Committee (IRC) Assessments | 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 | 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). |
| Best Overall Response Rate (KRAS Wild-Type Population) - Independent Review Committee (IRC) Assessments | 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 | 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). |
| Best Overall Response Rate (KRAS Mutant Population) - Independent Review Committee (IRC) Assessments | 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 | 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). |
| Disease Control Rate - Independent Review Committee (IRC) Assessments | 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 | 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). |
| Overall Survival Time (OS) | 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 | 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. |
| Participants With No Residual Tumor After Metastatic Surgery | 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 | Participants with no residual tumor after on-study surgery for metastases |
| Quality of Life (QOL) Assessment European Organisation for the Research and Treatment of Cancer (EORTC) QLQ-C30 Global Health Status | 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 | 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 | 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 | 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. |
| Safety - Number of Patients Experiencing Any Adverse Event | 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 | Please refer to Adverse Events section for further details |
| Duration of Response - Independent Review Committee (IRC) Assessments | 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 | 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. |
| Overall Survival Time (KRAS Wild-Type Population) | 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 | 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. |
| Overall Survival Time (KRAS Mutant Population) | 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 | 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. |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Chile, Czechia, Finland, France, Germany, Greece, Hong Kong, Hungary, Italy, Mexico, Netherlands, Poland, Romania, Russia, Singapore, Slovakia, South Africa, South Korea, Spain, Sweden, Taiwan, Turkey (Türkiye), Ukraine, United Kingdom
Participant flow
Recruitment details
First/Last subject in: 10 Aug 2004/4 Nov 2005. Clinical cut-off efficacy analyses except survival: 27 Jul 2006, Cut off date IRC data: 14 Dec 2006; cut-off safety analyses: 30 Nov 2007; cut-off survival analyses: 31 May 2009; cut-off KRAS analyses: 28 Aug 2009. 1221 subjects were randomised or treated, of whom 1198 were randomised and treated.
Pre-assignment details
At the prescreening visit the subject completed the first informed consent form, and a sample of tumor tissue for determination of EGFR expression was to be obtained. The screening (baseline) visit was performed no more than 21 days before randomization. EGFR-expressing subjects completed a second informed consent form to participate in the study.
Participants by arm
| Arm | Count |
|---|---|
| Cetuximab Plus FOLFIRI Cetuximab intravenous infusion of 400mg/m\^2 for the first infusion then weekly intravenous infusion of 250mg/m\^2. 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 | 599 |
| FOLFIRI Alone 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 | 599 |
| Total | 1,198 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | investigational study phase ongoing | 7 | 2 |
Baseline characteristics
| Characteristic | FOLFIRI Alone | Cetuximab Plus FOLFIRI | Total |
|---|---|---|---|
| Age, Continuous | 59.8 years STANDARD_DEVIATION 11.06 | 60.0 years STANDARD_DEVIATION 10.52 | 59.9 years STANDARD_DEVIATION 10.79 |
| Age, Customized >=65 years | 222 participants | 224 participants | 446 participants |
| Age, Customized Between 18 and 65 years | 377 participants | 374 participants | 751 participants |
| Age, Customized Missing | 0 participants | 1 participants | 1 participants |
| Gender Female | 243 Participants | 230 Participants | 473 Participants |
| Gender Male | 356 Participants | 369 Participants | 725 Participants |
| Region of Enrollment Eastern Europe | 201 participants | 203 participants | 404 participants |
| Region of Enrollment Rest of the World | 131 participants | 134 participants | 265 participants |
| Region of Enrollment Western Europe | 267 participants | 262 participants | 529 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 593 / 600 | 591 / 602 |
| serious Total, serious adverse events | 263 / 600 | 204 / 602 |
Outcome results
Primary
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
Population: Primary analysis on Intent to Treat (ITT) population i.e. all randomized subjects who have received at least one dose of randomized treatment (allocation to treatment groups as randomized).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cetuximab Plus FOLFIRI | Progression-free Survival (PFS) Time - Independent Review Committee (IRC) Assessments | 8.9 months |
| FOLFIRI Alone | Progression-free Survival (PFS) Time - Independent Review Committee (IRC) Assessments | 8.0 months |
Comparison: The study was planned with 633 progression events, in order to provide 80% power to test the null hypothesis of no difference in PFS time between treatment groups, assuming a hazard ratio (HR) of 0.8 of cetuximab + chemotherapy (CTX) over CTX alone. Significance level was fixed at 5%. The two-sided stratified log-rank test was employed, considering the randomization strata (region: Western Europe, Eastern Europe, outside Europe and Karnovsky Performance Scale (KPS):\<80 vs. ≥80)p-value: 0.047995% CI: [0.728, 1]Stratified log rank
Primary
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
Population: Intent to Treat (ITT) population with KRAS Wild Type tumor status as collected until 28 August 2009
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cetuximab Plus FOLFIRI | Progression-free Survival Time (Chinese V-Ki-ras2 Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) Wild-Type Population) - Independent Review Committee (IRC) Assessments | 9.9 months |
| FOLFIRI Alone | Progression-free Survival Time (Chinese V-Ki-ras2 Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) Wild-Type Population) - Independent Review Committee (IRC) Assessments | 8.4 months |
Comparison: The two-sided stratified log-rank test was employed at the 5% significance level, considering the randomization strata (region: Western Europe, Eastern Europe, outside Europe and KPS:\<80 vs. ≥80)p-value: 0.001295% CI: [0.558, 0.867]Stratified log rank
Primary
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
Population: Intent to Treat (ITT) population with KRAS Mutant tumor status as collected until 28 August 2009
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cetuximab Plus FOLFIRI | Progression-free Survival Time (KRAS Mutant Population) - Independent Review Committee (IRC) Assessments | 7.4 months |
| FOLFIRI Alone | Progression-free Survival Time (KRAS Mutant Population) - Independent Review Committee (IRC) Assessments | 7.7 months |
Comparison: The two-sided stratified log-rank test was employed at the 5% significance level, considering the randomization strata (region: Western Europe, Eastern Europe, outside Europe and KPS:\<80 vs. ≥80)p-value: 0.264895% CI: [0.887, 1.544]Stratified log rank
Secondary
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
Population: ITT population (allocation to treatment groups as randomized and treated)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cetuximab Plus FOLFIRI | Best Overall Response Rate - Independent Review Committee (IRC) Assessments | 46.9 percentage of participants |
| FOLFIRI Alone | Best Overall Response Rate - Independent Review Committee (IRC) Assessments | 38.7 percentage of participants |
Comparison: The two-sided stratified Cochran-Mantel-Haenszel (CMH) test was employed at the 5% significance level, considering the randomization strata (region: Western Europe, Eastern Europe, outside Europe and KPS:\<80 vs. ≥80)p-value: 0.003895% CI: [1.12, 1.77]Stratified cochran-mantel haenszel test
Secondary
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
Population: Intent to Treat (ITT) population with KRAS Mutant tumor status as collected until 28 August 2009
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cetuximab Plus FOLFIRI | Best Overall Response Rate (KRAS Mutant Population) - Independent Review Committee (IRC) Assessments | 31.3 percentage of participants |
| FOLFIRI Alone | Best Overall Response Rate (KRAS Mutant Population) - Independent Review Committee (IRC) Assessments | 36.1 percentage of participants |
Comparison: The two-sided stratified Cochran-Mantel-Haenszel (CMH) test was employed at the 5% significance level, considering the randomization strata (region: Western Europe, Eastern Europe, outside Europe and KPS:\<80 vs. ≥80)p-value: 0.347595% CI: [0.544, 1.242]Cochran-Mantel-Haenszel
Secondary
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
Population: Intent to Treat (ITT) population with KRAS Wild Type tumor status as collected until 28 August 2009
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cetuximab Plus FOLFIRI | Best Overall Response Rate (KRAS Wild-Type Population) - Independent Review Committee (IRC) Assessments | 57.3 percentage participants |
| FOLFIRI Alone | Best Overall Response Rate (KRAS Wild-Type Population) - Independent Review Committee (IRC) Assessments | 39.7 percentage participants |
Comparison: The two-sided stratified Cochran-Mantel-Haenszel (CMH) test was employed at the 5% significance level, considering the randomization strata (region: Western Europe, Eastern Europe, outside Europe and KPS:\<80 vs. ≥80)p-value: <0.000195% CI: [1.515, 2.826]Cochran-Mantel-Haenszel
Secondary
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
Population: ITT population (allocation to treatment groups as randomized and treated)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cetuximab Plus FOLFIRI | Disease Control Rate - Independent Review Committee (IRC) Assessments | 84.3 percentage of participants |
| FOLFIRI Alone | Disease Control Rate - Independent Review Committee (IRC) Assessments | 85.5 percentage of participants |
Comparison: The two-sided stratified Cochran-Mantel-Haenszel (CMH) test was employed at the 5% significance level, considering the randomization strata (region: Western Europe, Eastern Europe, outside Europe and KPS:\<80 vs. ≥80)p-value: 0.600495% CI: [0.67, 1.26]Stratified cochran-mantel haenszel test
Secondary
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
Population: ITT population (allocation to treatment groups as randomized and treated)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cetuximab Plus FOLFIRI | Duration of Response - Independent Review Committee (IRC) Assessments | 9.6 months |
| FOLFIRI Alone | Duration of Response - Independent Review Committee (IRC) Assessments | 7.7 months |
Secondary
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
Population: Intent to Treat (ITT) population with KRAS Mutant tumor status as collected until 28 August 2009
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cetuximab Plus FOLFIRI | Overall Survival Time (KRAS Mutant Population) | 16.2 months |
| FOLFIRI Alone | Overall Survival Time (KRAS Mutant Population) | 16.7 months |
Comparison: The two-sided stratified log-rank test was employed at the 5% significance level, considering the randomization strata (region: Western Europe, Eastern Europe, outside Europe and KPS:\<80 vs. ≥80)p-value: 0.754995% CI: [0.834, 1.284]Stratified log rank
Secondary
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
Population: Intent to Treat (ITT) population with KRAS Wild Type tumor status as collected until 28 August 2009
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cetuximab Plus FOLFIRI | Overall Survival Time (KRAS Wild-Type Population) | 23.5 months |
| FOLFIRI Alone | Overall Survival Time (KRAS Wild-Type Population) | 20.0 months |
Comparison: The two-sided stratified log-rank test was employed at the 5% significance level, considering the randomization strata (region: Western Europe, Eastern Europe, outside Europe and KPS:\<80 vs. ≥80)p-value: 0.009395% CI: [0.67, 0.946]Stratified log rank
Secondary
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
Population: ITT population (allocation to treatment groups as randomized and treated)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cetuximab Plus FOLFIRI | Overall Survival Time (OS) | 19.9 months |
| FOLFIRI Alone | Overall Survival Time (OS) | 18.6 months |
Comparison: The two-sided stratified log-rank test was employed at the 5% significance level, considering the randomization strata (region: Western Europe, Eastern Europe, outside Europe and KPS:\<80 vs. ≥80)p-value: 0.041995% CI: [0.774, 0.995]Stratified log rank
Secondary
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
Population: ITT population (allocation to treatment groups as randomized and treated)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cetuximab Plus FOLFIRI | Participants With No Residual Tumor After Metastatic Surgery | 29 Participants |
| FOLFIRI Alone | Participants With No Residual Tumor After Metastatic Surgery | 10 Participants |
p-value: 0.00295% CI: [1.45, 6.27]Cochran-Mantel-Haenszel
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 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
Population: 1125 subjects (566 in the Cetuximab + FOLFIRI arm and 559 in the FOLFIRI alone arm) completed at least one evaluable QLQ-C30 questionnaire and were thus included in the Evaluable for QLQ-C30 population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Cetuximab Plus FOLFIRI | Quality of Life Assessment (EORTC QLQ-C30) Social Functioning | At week 8 | 74.14 scores on a scale | Standard Error 1.43 |
| Cetuximab Plus FOLFIRI | Quality of Life Assessment (EORTC QLQ-C30) Social Functioning | At week 24 | 76.31 scores on a scale | Standard Error 1.644 |
| Cetuximab Plus FOLFIRI | Quality of Life Assessment (EORTC QLQ-C30) Social Functioning | At baseline | 75.21 scores on a scale | Standard Error 1.426 |
| Cetuximab Plus FOLFIRI | Quality of Life Assessment (EORTC QLQ-C30) Social Functioning | At week 16 | 73.72 scores on a scale | Standard Error 1.533 |
| Cetuximab Plus FOLFIRI | Quality of Life Assessment (EORTC QLQ-C30) Social Functioning | At week 40 | 76.58 scores on a scale | Standard Error 2.198 |
| Cetuximab Plus FOLFIRI | Quality of Life Assessment (EORTC QLQ-C30) Social Functioning | At week 32 | 74.04 scores on a scale | Standard Error 1.903 |
| FOLFIRI Alone | Quality of Life Assessment (EORTC QLQ-C30) Social Functioning | At week 40 | 78.07 scores on a scale | Standard Error 2.388 |
| FOLFIRI Alone | Quality of Life Assessment (EORTC QLQ-C30) Social Functioning | At baseline | 77.28 scores on a scale | Standard Error 1.395 |
| FOLFIRI Alone | Quality of Life Assessment (EORTC QLQ-C30) Social Functioning | At week 8 | 76.71 scores on a scale | Standard Error 1.415 |
| FOLFIRI Alone | Quality of Life Assessment (EORTC QLQ-C30) Social Functioning | At week 16 | 76.67 scores on a scale | Standard Error 1.498 |
| FOLFIRI Alone | Quality of Life Assessment (EORTC QLQ-C30) Social Functioning | At week 24 | 77.98 scores on a scale | Standard Error 1.633 |
| FOLFIRI Alone | Quality of Life Assessment (EORTC QLQ-C30) Social Functioning | At week 32 | 75.64 scores on a scale | Standard Error 1.933 |
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.
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
Population: 1125 subjects (566 Cetuximab + FOLFIRI; 559 FOLFIRI alone) completed at least 1 evaluable questionnaire \& were included in the Evaluable for QLQ-C30 population. Numbers at each timepoint were (Cetuximab + FOLFORI/FOLFORI alone, respectively): baseline 430/423; Week 8 421/390; Week 16 312/309; Week 24 255/244; Week 32 164/154; Week 40 122/96
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Cetuximab Plus FOLFIRI | Quality of Life (QOL) Assessment European Organisation for the Research and Treatment of Cancer (EORTC) QLQ-C30 Global Health Status | At baseline | 58.88 scores on a scale | Standard Error 1.185 |
| Cetuximab Plus FOLFIRI | Quality of Life (QOL) Assessment European Organisation for the Research and Treatment of Cancer (EORTC) QLQ-C30 Global Health Status | At week 8 | 59.02 scores on a scale | Standard Error 1.187 |
| Cetuximab Plus FOLFIRI | Quality of Life (QOL) Assessment European Organisation for the Research and Treatment of Cancer (EORTC) QLQ-C30 Global Health Status | At week 16 | 60.77 scores on a scale | Standard Error 1.276 |
| Cetuximab Plus FOLFIRI | Quality of Life (QOL) Assessment European Organisation for the Research and Treatment of Cancer (EORTC) QLQ-C30 Global Health Status | At week 24 | 61.83 scores on a scale | Standard Error 1.368 |
| Cetuximab Plus FOLFIRI | Quality of Life (QOL) Assessment European Organisation for the Research and Treatment of Cancer (EORTC) QLQ-C30 Global Health Status | At week 32 | 59.68 scores on a scale | Standard Error 1.59 |
| Cetuximab Plus FOLFIRI | Quality of Life (QOL) Assessment European Organisation for the Research and Treatment of Cancer (EORTC) QLQ-C30 Global Health Status | At week 40 | 63.43 scores on a scale | Standard Error 1.835 |
| FOLFIRI Alone | Quality of Life (QOL) Assessment European Organisation for the Research and Treatment of Cancer (EORTC) QLQ-C30 Global Health Status | At week 32 | 65.07 scores on a scale | Standard Error 1.612 |
| FOLFIRI Alone | Quality of Life (QOL) Assessment European Organisation for the Research and Treatment of Cancer (EORTC) QLQ-C30 Global Health Status | At baseline | 60.33 scores on a scale | Standard Error 1.155 |
| FOLFIRI Alone | Quality of Life (QOL) Assessment European Organisation for the Research and Treatment of Cancer (EORTC) QLQ-C30 Global Health Status | At week 24 | 64.06 scores on a scale | Standard Error 1.364 |
| FOLFIRI Alone | Quality of Life (QOL) Assessment European Organisation for the Research and Treatment of Cancer (EORTC) QLQ-C30 Global Health Status | At week 8 | 61.83 scores on a scale | Standard Error 1.176 |
| FOLFIRI Alone | Quality of Life (QOL) Assessment European Organisation for the Research and Treatment of Cancer (EORTC) QLQ-C30 Global Health Status | At week 40 | 64.02 scores on a scale | Standard Error 1.991 |
| FOLFIRI Alone | Quality of Life (QOL) Assessment European Organisation for the Research and Treatment of Cancer (EORTC) QLQ-C30 Global Health Status | At week 16 | 63.29 scores on a scale | Standard Error 1.249 |
Secondary
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
Population: Safety Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cetuximab Plus FOLFIRI | Safety - Number of Patients Experiencing Any Adverse Event | 599 participants |
| FOLFIRI Alone | Safety - Number of Patients Experiencing Any Adverse Event | 597 participants |