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

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ClinicalTrials.gov Identifier: NCT00125034
Recruitment Status : Completed
First Posted : July 29, 2005
Results First Posted : October 4, 2011
Last Update Posted : August 7, 2014
Sponsor:
Information provided by (Responsible Party):
Merck KGaA, Darmstadt, Germany

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Neoplasm Metastasis
Colorectal Cancer
Interventions Biological: Cetuximab
Drug: Oxaliplatin
Enrollment 344
Recruitment Details First & last subject randomized: 27 Jul 2005 & 8 Mar 2006, respectively. Primary outcome and disease control rate cut-off dates 4 Aug 2006, others: 1 Mar 2007; except overall survival, KRAS overall survival and KRAS progression-free survival outcomes, metastatic surgery outcome and adverse events: 30 Nov 2008.
Pre-assignment Details 629 subjects were prescreened, of whom 344 subjects were randomised. 338 subjects (Safety Population) received treatment. One subject was erroneously randomized, and was excluded from the ITT population (337 subjects).
Arm/Group Title Cetuximab Plus FOLFOX-4 FOLFOX-4 Alone
Hide Arm/Group Description Cetuximab plus 5-Fluorouracil(5-FU)/Folinic acid (FA) and oxaliplatin. Cetuximab will always be administered first, followed by oxaliplatin at least 1 hour later. Following completion of the oxaliplatin infusion or simultaneously with oxaliplatin 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-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. Safety population: includes all treated subjects. 5-FU/FA and oxaliplatin. 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. Safety population: includes all treated subjects.
Period Title: Overall Study
Started 170 [1] 168 [2]
Completed 170 168
Not Completed 0 0
[1]
Randomized & treated. 1 subject was not randomized correctly and was excluded in the ITT population.
[2]
Randomized & treated
Arm/Group Title Cetuximab Plus FOLFOX-4 FOLFOX-4 Alone Total
Hide Arm/Group Description Cetuximab plus 5-Fluorouracil(5-FU)/Folinic acid (FA) and oxaliplatin. Cetuximab will always be administered first, followed by oxaliplatin at least 1 hour later. Following completion of the oxaliplatin infusion or simultaneously with oxaliplatin 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-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. Safety population: includes all treated subjects. 5-FU/FA and oxaliplatin. 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. Safety population: includes all treated subjects. Total of all reporting groups
Overall Number of Baseline Participants 169 168 337
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 169 participants 168 participants 337 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
96
  56.8%
109
  64.9%
205
  60.8%
>=65 years
73
  43.2%
59
  35.1%
132
  39.2%
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 169 participants 168 participants 337 participants
62.0
(24 to 82)
60.0
(30 to 82)
61.0
(24 to 82)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 169 participants 168 participants 337 participants
Female
80
  47.3%
76
  45.2%
156
  46.3%
Male
89
  52.7%
92
  54.8%
181
  53.7%
Region of Enrollment   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 169 participants 168 participants 337 participants
Portugal 0 3 3
Spain 19 16 35
Ukraine 24 25 49
Austria 16 9 25
Russian Federation 25 24 49
Israel 0 1 1
Italy 8 6 14
France 3 12 15
Belgium 12 6 18
Poland 30 31 61
Romania 18 13 31
Germany 14 22 36
[1]
Measure Description: Figures refer to randomized and treated participants
1.Primary Outcome
Title Best Overall Response Rate - Independent Review Committee (IRC)
Hide Description 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.
Time Frame 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Primary analysis on the 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/Group Title Cetuximab Plus FOLFOX-4 FOLFOX-4 Alone
Hide Arm/Group Description:
Cetuximab plus 5-Fluorouracil(5-FU)/Folinic acid (FA) and oxaliplatin. Cetuximab will always be administered first, followed by oxaliplatin at least 1 hour later. Following completion of the oxaliplatin infusion or simultaneously with oxaliplatin 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-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. Safety population: includes all treated subjects.
5-FU/FA and oxaliplatin. 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. Safety population: includes all treated subjects.
Overall Number of Participants Analyzed 169 168
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
45.6
(37.9 to 53.4)
35.7
(28.5 to 43.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cetuximab Plus FOLFOX-4, FOLFOX-4 Alone
Comments Assuming a difference in rate of best confirmed response of at least 20% between the 2 treatments, ie an approximately 70% response rate under cetuximab plus FOLFOX-4 & 50% under FOLFOX-4 alone for the stratum with ECOG PS0–1 & 66% and 45% respectively for the ECOG PS2 stratum, the common OddsR over the strata was expected to be 2.33. A sample size of approximately 146/group was calculated as necessary to detect a significant overall response of at least 2.33 at level α=0.05 with a power of 90%
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.064
Comments [Not Specified]
Method stratified Cochran-Mantel-Haenszel test
Comments Stratified odds ratio and Cochran-Mantel-Haenszel (CMH) statistics were calculated considering the randomization strata.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.516
Confidence Interval (2-Sided) 95%
0.975 to 2.335
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Best Overall Response Rate (Chinese V-Ki-ras2 Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) Wild-Type Population)
Hide Description 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.
Time Frame 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
KRAS Wild-Type population
Arm/Group Title Cetuximab Plus FOLFOX-4 FOLFOX-4 Alone
Hide Arm/Group Description:
Cetuximab plus 5-Fluorouracil(5-FU)/Folinic acid (FA) and oxaliplatin. Cetuximab will always be administered first, followed by oxaliplatin at least 1 hour later. Following completion of the oxaliplatin infusion or simultaneously with oxaliplatin 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-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. Safety population: includes all treated subjects.
5-FU/FA and oxaliplatin. 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. Safety population: includes all treated subjects.
Overall Number of Participants Analyzed 82 97
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
57.3
(45.9 to 68.2)
34.0
(24.7 to 44.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cetuximab Plus FOLFOX-4, FOLFOX-4 Alone
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0027
Comments [Not Specified]
Method stratified Cochran-Mantel-Haenszel test
Comments Stratified odds ratio and Cochran-Mantel-Haenszel (CMH) statistics were calculated considering the randomization strata.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.551
Confidence Interval (2-Sided) 95%
1.380 to 4.717
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Best Overall Response Rate (KRAS Mutant Population)
Hide Description 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.
Time Frame 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
KRAS Mutant population
Arm/Group Title Cetuximab Plus FOLFOX-4 FOLFOX-4 Alone
Hide Arm/Group Description:
Cetuximab plus 5-Fluorouracil(5-FU)/Folinic acid (FA) and oxaliplatin. Cetuximab will always be administered first, followed by oxaliplatin at least 1 hour later. Following completion of the oxaliplatin infusion or simultaneously with oxaliplatin 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-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. Safety population: includes all treated subjects.
5-FU/FA and oxaliplatin. 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. Safety population: includes all treated subjects.
Overall Number of Participants Analyzed 77 59
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
33.8
(23.4 to 45.5)
52.5
(39.1 to 65.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cetuximab Plus FOLFOX-4, FOLFOX-4 Alone
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0290
Comments [Not Specified]
Method stratified Cochran-Mantel-Haenszel test
Comments Stratified odds ratio and Cochran-Mantel-Haenszel (CMH) statistics were calculated considering the randomization strata.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.459
Confidence Interval (2-Sided) 95%
0.228 to 0.924
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Progression-free Survival Time
Hide Description

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 Frame 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Primary analysis on ITT population i.e. all randomized subjects who have received at least one dose of randomized treatment (allocation to treatment groups as randomized).
Arm/Group Title Cetuximab Plus FOLFOX-4 FOLFOX-4 Alone
Hide Arm/Group Description:
Cetuximab plus 5-Fluorouracil(5-FU)/Folinic acid (FA) and oxaliplatin. Cetuximab will always be administered first, followed by oxaliplatin at least 1 hour later. Following completion of the oxaliplatin infusion or simultaneously with oxaliplatin 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-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. Safety population: includes all treated subjects.
5-FU/FA and oxaliplatin. 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. Safety population: includes all treated subjects.
Overall Number of Participants Analyzed 169 168
Median (95% Confidence Interval)
Unit of Measure: months
7.2
(5.6 to 7.7)
7.2
(6.0 to 7.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cetuximab Plus FOLFOX-4, FOLFOX-4 Alone
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6170
Comments [Not Specified]
Method Stratified Log Rank
Comments Kaplan-Meier method used to estimate median OS time. HR was calculated using Cox proportional hazards model stratified by randomization strata.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.931
Confidence Interval (2-Sided) 95%
0.705 to 1.230
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Progression-free Survival Time (KRAS Wild-Type Population)
Hide Description

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 Frame 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
KRAS Wild-Type population
Arm/Group Title Cetuximab Plus FOLFOX-4 FOLFOX-4 Alone
Hide Arm/Group Description:
Cetuximab plus 5-Fluorouracil(5-FU)/Folinic acid (FA) and oxaliplatin. Cetuximab will always be administered first, followed by oxaliplatin at least 1 hour later. Following completion of the oxaliplatin infusion or simultaneously with oxaliplatin 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-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. Safety population: includes all treated subjects.
5-FU/FA and oxaliplatin. 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. Safety population: includes all treated subjects.
Overall Number of Participants Analyzed 82 97
Median (95% Confidence Interval)
Unit of Measure: months
8.3
(7.2 to 12.0)
7.2
(5.6 to 7.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cetuximab Plus FOLFOX-4, FOLFOX-4 Alone
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0064
Comments [Not Specified]
Method Stratified Log Rank
Comments Kaplan-Meier method used to estimate median OS time. HR was calculated using Cox proportional hazards model stratified by randomization strata.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.567
Confidence Interval (2-Sided) 95%
0.375 to 0.856
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Progression-free Survival Time (KRAS Mutant Population)
Hide Description

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 Frame 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
KRAS Mutant population
Arm/Group Title Cetuximab Plus FOLFOX-4 FOLFOX-4 Alone
Hide Arm/Group Description:
Cetuximab plus 5-Fluorouracil(5-FU)/Folinic acid (FA) and oxaliplatin. Cetuximab will always be administered first, followed by oxaliplatin at least 1 hour later. Following completion of the oxaliplatin infusion or simultaneously with oxaliplatin 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-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. Safety population: includes all treated subjects.
5-FU/FA and oxaliplatin. 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. Safety population: includes all treated subjects.
Overall Number of Participants Analyzed 77 59
Median (95% Confidence Interval)
Unit of Measure: months
5.5
(4.0 to 7.3)
8.6
(6.5 to 9.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cetuximab Plus FOLFOX-4, FOLFOX-4 Alone
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0153
Comments [Not Specified]
Method Stratified Log Rank
Comments Kaplan-Meier method used to estimate median OS time. HR was calculated using Cox proportional hazards model stratified by randomization strata.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.720
Confidence Interval (2-Sided) 95%
1.104 to 2.679
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Overall Survival Time
Hide Description 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 Frame 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Primary analysis on ITT population i.e. all randomized subjects who have received at least one dose of randomized treatment (allocation to treatment groups as randomized).
Arm/Group Title Cetuximab Plus FOLFOX-4 FOLFOX-4 Alone
Hide Arm/Group Description:
Cetuximab plus 5-Fluorouracil(5-FU)/Folinic acid (FA) and oxaliplatin. Cetuximab will always be administered first, followed by oxaliplatin at least 1 hour later. Following completion of the oxaliplatin infusion or simultaneously with oxaliplatin 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-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. Safety population: includes all treated subjects.
5-FU/FA and oxaliplatin. 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. Safety population: includes all treated subjects.
Overall Number of Participants Analyzed 169 168
Median (95% Confidence Interval)
Unit of Measure: months
18.3
(14.8 to 20.4)
18.0
(16.7 to 21.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cetuximab Plus FOLFOX-4, FOLFOX-4 Alone
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9050
Comments [Not Specified]
Method Stratified log rank
Comments Kaplan-Meier method used to estimate median OS time. HR was calculated using Cox proportional hazards model stratified by randomization strata.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.015
Confidence Interval (2-Sided) 95%
0.791 to 1.303
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Overall Survival Time (KRAS Wild-Type Population)
Hide Description 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 Frame 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
KRAS Wild-Type population
Arm/Group Title Cetuximab Plus FOLFOX-4 FOLFOX-4 Alone
Hide Arm/Group Description:
Cetuximab plus 5-Fluorouracil(5-FU)/Folinic acid (FA) and oxaliplatin. Cetuximab will always be administered first, followed by oxaliplatin at least 1 hour later. Following completion of the oxaliplatin infusion or simultaneously with oxaliplatin 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-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. Safety population: includes all treated subjects.
5-FU/FA and oxaliplatin. 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. Safety population: includes all treated subjects.
Overall Number of Participants Analyzed 82 97
Median (95% Confidence Interval)
Unit of Measure: months
22.8
(19.3 to 25.9)
18.5
(16.4 to 22.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cetuximab Plus FOLFOX-4, FOLFOX-4 Alone
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3854
Comments [Not Specified]
Method Stratified log rank
Comments Kaplan-Meier method used to estimate median OS time. HR was calculated using Cox proportional hazards model stratified by randomization strata.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.855
Confidence Interval (2-Sided) 95%
0.599 to 1.219
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Overall Survival Time (KRAS Mutant Population)
Hide Description 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 Frame 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
KRAS Mutant population
Arm/Group Title Cetuximab Plus FOLFOX-4 FOLFOX-4 Alone
Hide Arm/Group Description:
Cetuximab plus 5-Fluorouracil(5-FU)/Folinic acid (FA) and oxaliplatin. Cetuximab will always be administered first, followed by oxaliplatin at least 1 hour later. Following completion of the oxaliplatin infusion or simultaneously with oxaliplatin 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-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. Safety population: includes all treated subjects.
5-FU/FA and oxaliplatin. 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. Safety population: includes all treated subjects.
Overall Number of Participants Analyzed 77 59
Median (95% Confidence Interval)
Unit of Measure: months
13.4
(10.5 to 17.7)
17.5
(14.7 to 24.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cetuximab Plus FOLFOX-4, FOLFOX-4 Alone
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2004
Comments [Not Specified]
Method Stratified log rank
Comments Kaplan-Meier method used to estimate median OS time. HR was calculated using Cox proportional hazards model stratified by randomization strata.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.290
Confidence Interval (2-Sided) 95%
0.873 to 1.906
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Participants With No Residual Tumor After Metastatic Surgery
Hide Description No residual tumor after on-study surgery for metastases.
Time Frame 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
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Hide Analysis Population Description
Primary analysis on ITT population i.e. all randomized subjects who have received at least one dose of randomized treatment (allocation to treatment groups as randomized).
Arm/Group Title Cetuximab Plus FOLFOX-4 FOLFOX-4 Alone
Hide Arm/Group Description:
Cetuximab plus 5-Fluorouracil(5-FU)/Folinic acid (FA) and oxaliplatin. Cetuximab will always be administered first, followed by oxaliplatin at least 1 hour later. Following completion of the oxaliplatin infusion or simultaneously with oxaliplatin 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-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. Safety population: includes all treated subjects.
5-FU/FA and oxaliplatin. 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. Safety population: includes all treated subjects.
Overall Number of Participants Analyzed 169 168
Measure Type: Number
Unit of Measure: participants
8 4
11.Secondary Outcome
Title Disease Control Rate (Cut Off Date 4 August 2006)
Hide Description 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).
Time Frame 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
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Hide Analysis Population Description
Primary analysis on ITT population i.e. all randomized subjects who have received at least one dose of randomized treatment (allocation to treatment groups as randomized).
Arm/Group Title Cetuximab Plus FOLFOX-4 FOLFOX-4 Alone
Hide Arm/Group Description:
Cetuximab plus 5-Fluorouracil(5-FU)/Folinic acid (FA) and oxaliplatin. Cetuximab will always be administered first, followed by oxaliplatin at least 1 hour later. Following completion of the oxaliplatin infusion or simultaneously with oxaliplatin 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-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. Safety population: includes all treated subjects.
5-FU/FA and oxaliplatin. 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. Safety population: includes all treated subjects.
Overall Number of Participants Analyzed 169 168
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
85.2
(78.9 to 90.2)
81.0
(74.2 to 86.6)
12.Secondary Outcome
Title Duration of Response
Hide Description

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, 27 Jul 2005, until cut-off date 01 Mar 2007
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Hide Analysis Population Description
Primary analysis on ITT population i.e. all randomized subjects who have received at least one dose of randomized treatment (allocation to treatment groups as randomized).
Arm/Group Title Cetuximab Plus FOLFOX-4 FOLFOX-4 Alone
Hide Arm/Group Description:
Cetuximab plus 5-Fluorouracil(5-FU)/Folinic acid (FA) and oxaliplatin. Cetuximab will always be administered first, followed by oxaliplatin at least 1 hour later. Following completion of the oxaliplatin infusion or simultaneously with oxaliplatin 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-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. Safety population: includes all treated subjects.
5-FU/FA and oxaliplatin. 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. Safety population: includes all treated subjects.
Overall Number of Participants Analyzed 169 168
Median (95% Confidence Interval)
Unit of Measure: months
9.0
(5.9 to 11.1)
5.7
(5.4 to 7.7)
13.Secondary Outcome
Title Safety - Number of Patients Experiencing Any Adverse Event
Hide Description Please refer to Adverse Events section for further details
Time Frame 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
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Hide Analysis Population Description
Safety Population
Arm/Group Title Cetuximab Plus FOLFOX-4 FOLFOX-4 Alone
Hide Arm/Group Description:
Cetuximab plus 5-Fluorouracil(5-FU)/Folinic acid (FA) and oxaliplatin. Cetuximab will always be administered first, followed by oxaliplatin at least 1 hour later. Following completion of the oxaliplatin infusion or simultaneously with oxaliplatin 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-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. Safety population: includes all treated subjects.
5-FU/FA and oxaliplatin. 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. Safety population: includes all treated subjects.
Overall Number of Participants Analyzed 170 168
Measure Type: Number
Unit of Measure: participants
170 165
Time Frame Time from first dose up to 30 days after the last dose of study treatment.
Adverse Event Reporting Description Treatment-emergent adverse events were defined as those with onset occurring at or after the first dosing day of study medication and up to 30 days after the last administration of any study drug or the clinical cut-off date.
 
Arm/Group Title Cetuximab Plus FOLFOX-4 FOLFOX-4 Alone
Hide Arm/Group Description Cetuximab plus 5-Fluorouracil(5-FU)/Folinic acid (FA) and oxaliplatin. Cetuximab will always be administered first, followed by oxaliplatin at least 1 hour later. Following completion of the oxaliplatin infusion or simultaneously with oxaliplatin 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-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. Safety population: includes all treated subjects. 5-FU/FA and oxaliplatin. 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. Safety population: includes all treated subjects.
All-Cause Mortality
Cetuximab Plus FOLFOX-4 FOLFOX-4 Alone
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Cetuximab Plus FOLFOX-4 FOLFOX-4 Alone
Affected / at Risk (%) Affected / at Risk (%)
Total   61/170 (35.88%)   43/168 (25.60%) 
Blood and lymphatic system disorders     
ANAEMIA  1  0/170 (0.00%)  1/168 (0.60%) 
FEBRILE BONE MARROW APLASIA  1  0/170 (0.00%)  1/168 (0.60%) 
FEBRILE NEUTROPENIA  1  4/170 (2.35%)  3/168 (1.79%) 
LEUKOPENIA  1  3/170 (1.76%)  2/168 (1.19%) 
NEUTROPENIA  1  4/170 (2.35%)  5/168 (2.98%) 
THROMBOCYTOPENIA  1  0/170 (0.00%)  1/168 (0.60%) 
Cardiac disorders     
ACUTE MYOCARDIAL INFARCTION  1  1/170 (0.59%)  0/168 (0.00%) 
ARRHYTHMIA SUPRAVENTRICULAR  1  2/170 (1.18%)  0/168 (0.00%) 
ATRIAL FIBRILLATION  1  1/170 (0.59%)  0/168 (0.00%) 
CARDIAC FAILURE  1  1/170 (0.59%)  0/168 (0.00%) 
CARDIO-RESPIRATORY ARREST  1  2/170 (1.18%)  0/168 (0.00%) 
LEFT VENTRICULAR DYSFUNCTION  1  1/170 (0.59%)  0/168 (0.00%) 
Ear and labyrinth disorders     
VERTIGO  1  1/170 (0.59%)  0/168 (0.00%) 
Eye disorders     
CONJUNCTIVITIS  1  1/170 (0.59%)  0/168 (0.00%) 
Gastrointestinal disorders     
ABDOMINAL PAIN  1  2/170 (1.18%)  1/168 (0.60%) 
ASCITES  1  2/170 (1.18%)  0/168 (0.00%) 
COLITIS  1  1/170 (0.59%)  0/168 (0.00%) 
CONSTIPATION  1  2/170 (1.18%)  0/168 (0.00%) 
DIARRHOEA  1  2/170 (1.18%)  2/168 (1.19%) 
GASTROINTESTINAL PERFORATION  1  0/170 (0.00%)  1/168 (0.60%) 
HAEMATEMESIS  1  0/170 (0.00%)  1/168 (0.60%) 
ILEUS  1  4/170 (2.35%)  1/168 (0.60%) 
INTESTINAL OBSTRUCTION  1  3/170 (1.76%)  0/168 (0.00%) 
LARGE INTESTINAL OBSTRUCTION  1  1/170 (0.59%)  0/168 (0.00%) 
NAUSEA  1  0/170 (0.00%)  1/168 (0.60%) 
PANCREATITIS  1  1/170 (0.59%)  0/168 (0.00%) 
PERITONITIS  1  0/170 (0.00%)  1/168 (0.60%) 
RECTAL STENOSIS  1  0/170 (0.00%)  1/168 (0.60%) 
SUBILEUS  1  0/170 (0.00%)  1/168 (0.60%) 
VOMITING  1  2/170 (1.18%)  4/168 (2.38%) 
General disorders     
ASTHENIA  1  3/170 (1.76%)  1/168 (0.60%) 
CHEST PAIN  1  1/170 (0.59%)  0/168 (0.00%) 
FATIGUE  1  1/170 (0.59%)  1/168 (0.60%) 
GENERAL PHYSICAL HEALTH DETERIORATION  1  0/170 (0.00%)  1/168 (0.60%) 
INJECTION SITE REACTION  1  1/170 (0.59%)  0/168 (0.00%) 
MASS  1  1/170 (0.59%)  0/168 (0.00%) 
MUCOSAL INFLAMMATION  1  1/170 (0.59%)  0/168 (0.00%) 
OBSTRUCTION  1  0/170 (0.00%)  1/168 (0.60%) 
PYREXIA  1  4/170 (2.35%)  4/168 (2.38%) 
Hepatobiliary disorders     
BILE DUCT STONE  1  0/170 (0.00%)  1/168 (0.60%) 
CHOLANGITIS  1  1/170 (0.59%)  0/168 (0.00%) 
HEPATIC FAILURE  1  1/170 (0.59%)  0/168 (0.00%) 
HEPATORENAL SYNDROME  1  1/170 (0.59%)  0/168 (0.00%) 
HYPERBILIRUBINAEMIA  1  2/170 (1.18%)  0/168 (0.00%) 
JAUNDICE  1  1/170 (0.59%)  0/168 (0.00%) 
Immune system disorders     
HYPERSENSITIVITY  1  5/170 (2.94%)  2/168 (1.19%) 
Infections and infestations     
ABSCESS NECK  1  0/170 (0.00%)  1/168 (0.60%) 
BRONCHITIS  1  0/170 (0.00%)  1/168 (0.60%) 
CATHETER RELATED INFECTION  1  0/170 (0.00%)  1/168 (0.60%) 
CENTRAL LINE INFECTION  1  0/170 (0.00%)  1/168 (0.60%) 
ERYSIPELAS  1  2/170 (1.18%)  0/168 (0.00%) 
FEBRILE INFECTION  1  1/170 (0.59%)  0/168 (0.00%) 
INFECTION  1  2/170 (1.18%)  1/168 (0.60%) 
KIDNEY INFECTION  1  0/170 (0.00%)  1/168 (0.60%) 
LUNG ABSCESS  1  1/170 (0.59%)  0/168 (0.00%) 
PERITONITIS BACTERIAL  1  1/170 (0.59%)  0/168 (0.00%) 
PNEUMONIA  1  3/170 (1.76%)  3/168 (1.79%) 
PULMONARY TUBERCULOSIS  1  1/170 (0.59%)  0/168 (0.00%) 
PYELONEPHRITIS ACUTE  1  0/170 (0.00%)  1/168 (0.60%) 
SEPSIS  1  1/170 (0.59%)  0/168 (0.00%) 
STAPHYLOCOCCAL SEPSIS  1  1/170 (0.59%)  0/168 (0.00%) 
TUBERCULOSIS  1  1/170 (0.59%)  0/168 (0.00%) 
URINARY TRACT INFECTION  1  0/170 (0.00%)  1/168 (0.60%) 
Injury, poisoning and procedural complications     
FALL  1  1/170 (0.59%)  0/168 (0.00%) 
HUMERUS FRACTURE  1  1/170 (0.59%)  0/168 (0.00%) 
INCISIONAL HERNIA  1  1/170 (0.59%)  0/168 (0.00%) 
WOUND DEHISCENCE  1  1/170 (0.59%)  0/168 (0.00%) 
Metabolism and nutrition disorders     
ANOREXIA  1  3/170 (1.76%)  0/168 (0.00%) 
DEHYDRATION  1  2/170 (1.18%)  1/168 (0.60%) 
DIABETES MELLITUS INADEQUATE CONTROL  1  1/170 (0.59%)  0/168 (0.00%) 
HYPERGLYCAEMIA  1  1/170 (0.59%)  0/168 (0.00%) 
HYPOKALAEMIA  1  1/170 (0.59%)  0/168 (0.00%) 
Nervous system disorders     
DEPRESSED LEVEL OF CONSCIOUSNESS  1  2/170 (1.18%)  0/168 (0.00%) 
DIZZINESS  1  0/170 (0.00%)  1/168 (0.60%) 
EPILEPSY  1  0/170 (0.00%)  1/168 (0.60%) 
PERIPHERAL SENSORY NEUROPATHY  1  1/170 (0.59%)  0/168 (0.00%) 
SYNCOPE  1  1/170 (0.59%)  0/168 (0.00%) 
Psychiatric disorders     
ALCOHOLIC PSYCHOSIS  1  0/170 (0.00%)  1/168 (0.60%) 
Renal and urinary disorders     
RENAL FAILURE  1  1/170 (0.59%)  0/168 (0.00%) 
URINARY RETENTION  1  0/170 (0.00%)  1/168 (0.60%) 
Respiratory, thoracic and mediastinal disorders     
DYSPNOEA  1  1/170 (0.59%)  0/168 (0.00%) 
MEDIASTINAL HAEMATOMA  1  1/170 (0.59%)  0/168 (0.00%) 
PULMONARY EMBOLISM  1  5/170 (2.94%)  2/168 (1.19%) 
TACHYPNOEA  1  1/170 (0.59%)  0/168 (0.00%) 
Surgical and medical procedures     
ILEOCOLOSTOMY  1  0/170 (0.00%)  1/168 (0.60%) 
Vascular disorders     
AXILLARY VEIN THROMBOSIS  1  1/170 (0.59%)  0/168 (0.00%) 
CIRCULATORY COLLAPSE  1  0/170 (0.00%)  1/168 (0.60%) 
EMBOLISM  1  0/170 (0.00%)  1/168 (0.60%) 
HYPERTENSION  1  2/170 (1.18%)  0/168 (0.00%) 
HYPOTENSION  1  1/170 (0.59%)  0/168 (0.00%) 
INTERMITTENT CLAUDICATION  1  1/170 (0.59%)  0/168 (0.00%) 
PERIPHERAL ARTERIAL OCCLUSIVE DISEASE  1  1/170 (0.59%)  0/168 (0.00%) 
THROMBOPHLEBITIS  1  0/170 (0.00%)  1/168 (0.60%) 
VENOUS THROMBOSIS  1  1/170 (0.59%)  0/168 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (10.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Cetuximab Plus FOLFOX-4 FOLFOX-4 Alone
Affected / at Risk (%) Affected / at Risk (%)
Total   170/170 (100.00%)   165/168 (98.21%) 
Blood and lymphatic system disorders     
ANAEMIA  1  44/170 (25.88%)  41/168 (24.40%) 
LEUKOPENIA  1  49/170 (28.82%)  43/168 (25.60%) 
NEUTROPENIA  1  77/170 (45.29%)  84/168 (50.00%) 
THROMBOCYTOPENIA  1  45/170 (26.47%)  69/168 (41.07%) 
Ear and labyrinth disorders     
VERTIGO  1  9/170 (5.29%)  7/168 (4.17%) 
Eye disorders     
CONJUNCTIVITIS  1  23/170 (13.53%)  8/168 (4.76%) 
Gastrointestinal disorders     
ABDOMINAL PAIN  1  30/170 (17.65%)  29/168 (17.26%) 
CONSTIPATION  1  32/170 (18.82%)  16/168 (9.52%) 
DIARRHOEA  1  81/170 (47.65%)  68/168 (40.48%) 
DYSPEPSIA  1  9/170 (5.29%)  9/168 (5.36%) 
NAUSEA  1  69/170 (40.59%)  65/168 (38.69%) 
STOMATITIS  1  33/170 (19.41%)  19/168 (11.31%) 
VOMITING  1  48/170 (28.24%)  37/168 (22.02%) 
General disorders     
ASTHENIA  1  32/170 (18.82%)  31/168 (18.45%) 
FATIGUE  1  54/170 (31.76%)  43/168 (25.60%) 
MUCOSAL INFLAMMATION  1  22/170 (12.94%)  8/168 (4.76%) 
PYREXIA  1  39/170 (22.94%)  30/168 (17.86%) 
Immune system disorders     
HYPERSENSITIVITY  1  13/170 (7.65%)  1/168 (0.60%) 
Infections and infestations     
PARONYCHIA  1  20/170 (11.76%)  0/168 (0.00%) 
Investigations     
WEIGHT DECREASED  1  26/170 (15.29%)  19/168 (11.31%) 
Metabolism and nutrition disorders     
ANOREXIA  1  34/170 (20.00%)  23/168 (13.69%) 
HYPOCALCAEMIA  1  10/170 (5.88%)  0/168 (0.00%) 
HYPOKALAEMIA  1  11/170 (6.47%)  5/168 (2.98%) 
HYPOMAGNESAEMIA  1  16/170 (9.41%)  2/168 (1.19%) 
Musculoskeletal and connective tissue disorders     
BACK PAIN  1  10/170 (5.88%)  8/168 (4.76%) 
Nervous system disorders     
DIZZINESS  1  11/170 (6.47%)  3/168 (1.79%) 
HEADACHE  1  11/170 (6.47%)  8/168 (4.76%) 
NEUROPATHY  1  10/170 (5.88%)  16/168 (9.52%) 
NEUROTOXICITY  1  12/170 (7.06%)  7/168 (4.17%) 
PARAESTHESIA  1  19/170 (11.18%)  38/168 (22.62%) 
PERIPHERAL SENSORY NEUROPATHY  1  46/170 (27.06%)  51/168 (30.36%) 
POLYNEUROPATHY  1  9/170 (5.29%)  5/168 (2.98%) 
Psychiatric disorders     
INSOMNIA  1  9/170 (5.29%)  6/168 (3.57%) 
Respiratory, thoracic and mediastinal disorders     
COUGH  1  10/170 (5.88%)  7/168 (4.17%) 
EPISTAXIS  1  15/170 (8.82%)  11/168 (6.55%) 
Skin and subcutaneous tissue disorders     
ACNE  1  10/170 (5.88%)  0/168 (0.00%) 
ALOPECIA  1  21/170 (12.35%)  17/168 (10.12%) 
DERMATITIS ACNEIFORM  1  38/170 (22.35%)  1/168 (0.60%) 
DRY SKIN  1  28/170 (16.47%)  3/168 (1.79%) 
EXFOLIATIVE RASH  1  12/170 (7.06%)  0/168 (0.00%) 
NAIL DISORDER  1  11/170 (6.47%)  2/168 (1.19%) 
PALMAR-PLANTAR ERYTHRODYSAESTHESIA SYNDROME  1  19/170 (11.18%)  7/168 (4.17%) 
PRURITUS  1  15/170 (8.82%)  6/168 (3.57%) 
RASH  1  90/170 (52.94%)  4/168 (2.38%) 
SKIN FISSURES  1  17/170 (10.00%)  0/168 (0.00%) 
SKIN TOXICITY  1  13/170 (7.65%)  0/168 (0.00%) 
Vascular disorders     
HYPERTENSION  1  11/170 (6.47%)  8/168 (4.76%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (10.0)
A non-specific outcome measure 'Safety' was deleted from this entry in error. A replacement outcome has been created. The 'Safety' outcome refers to adverse events and these are shown in the 'Adverse Events' section.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Inmaculada Ollero/Clinical Trial Manager
Organization: Merck Serono
Phone: +34935655433
Responsible Party: Merck KGaA, Darmstadt, Germany
ClinicalTrials.gov Identifier: NCT00125034     History of Changes
Other Study ID Numbers: EMR 62202-047
First Submitted: July 28, 2005
First Posted: July 29, 2005
Results First Submitted: August 23, 2011
Results First Posted: October 4, 2011
Last Update Posted: August 7, 2014