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Trial record 1 of 1 for:    I4E-MC-JXBD
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A Study in Head and Neck Cancer

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ClinicalTrials.gov Identifier: NCT01081041
Recruitment Status : Completed
First Posted : March 5, 2010
Results First Posted : July 14, 2014
Last Update Posted : April 12, 2017
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Head and Neck Cancer
Interventions Drug: Cetuximab
Drug: Cisplatin
Drug: Carboplatin
Drug: 5-Fluorouracil
Enrollment 187
Recruitment Details  
Pre-assignment Details Two-part study: Part 1 (single arm, safety lead-in) then Part 2 (parallel treatment comparison). All participants to complete 6 cycles of combination therapy then, if eligible, monotherapy. Participant flow presents those who completed study (died); those who were alive or death status unknown at data cut-off considered to not have completed study.
Arm/Group Title Part 1: Safety Lead-In (Cetuximab, Cis or Carbo, 5-FU) Part 2: Cetuximab (US Commercial), Cis or Carbo, 5-FU Part 2: Cetuximab (Manufactured by BI), Cis or Carbo, 5-FU
Hide Arm/Group Description

Combination Therapy (maximum 6 cycles):

  • United States (US) commercial cetuximab, manufactured by ImClone, 400 milligrams per square meter (mg/m^2) intravenous (IV) infusion on Day 1 of Cycle 1; subsequently 250 mg/m^2 IV infusion weekly.
  • Cisplatin (cis) 100 mg/m^2 or carboplatin (carbo) area under the curve (AUC) 5, up to a maximum 750 mg dose, IV infusion on Day 1 of every 21-day cycle, 1 hour after cetuximab infusion.
  • 5-Fluorouracil (5-FU): 1000 mg/m^2 IV infusion on Days 1 through 4 of every 21-day cycle.

Monotherapy Therapy:

Participants who did not experience disease progression after 6 cycles of combination therapy continued on weekly US commercial cetuximab monotherapy 250 mg/m^2 until disease progression, unacceptable toxicity, or other withdrawal criteria were met.

Combination Therapy (maximum 6 cycles):

  • US commercial cetuximab, manufactured by ImClone, 400 mg/m^2 IV infusion on Day 1 of Cycle 1; subsequently 250 mg/m^2 IV infusion weekly.
  • Cis 100 mg/m^2 or carbo AUC 5, up to a maximum 750 mg dose, IV infusion on Day 1 of every 21-day cycle, 1 hour after cetuximab infusion.
  • 5-FU: 1000 mg/m^2 IV infusion on Days 1 through 4 of every 21-day cycle.

Monotherapy Therapy:

Participants who did not experience disease progression after 6 cycles of combination therapy continued on weekly US commercial cetuximab monotherapy 250 mg/m^2 until disease progression, unacceptable toxicity, or other withdrawal criteria were met.

Combination Therapy (maximum 6 cycles):

  • Cetuximab, manufactured by Boehringer Ingelheim (BI), 400 mg/m^2 IV infusion on Day 1 of Cycle 1; subsequently 250 mg/m^2 IV infusion weekly.
  • Cis 100 mg/m^2 or carbo AUC 5, up to a maximum 750 mg dose, IV infusion on Day 1 of every 21-day cycle, 1 hour after cetuximab infusion.
  • 5-FU: 1000 mg/m^2 IV infusion on Days 1 through 4 of every 21-day cycle.

Monotherapy Therapy:

Participants who did not experience disease progression after 6 cycles of combination therapy continued on weekly BI-manufactured cetuximab monotherapy 250 mg/m^2 until disease progression, unacceptable toxicity, or other withdrawal criteria were met.

Period Title: Overall Study
Started 33 81 73
Received at Least 1 Dose of Study Drug 33 77 71
Completed 33 77 71
Not Completed 0 4 2
Arm/Group Title Part 1: Safety Lead-In (Cetuximab, Cis or Carbo, 5-FU) Part 2: Cetuximab (US Commercial), Cis or Carbo, 5-FU Part 2: Cetuximab (Manufactured by BI), Cis or Carbo, 5-FU Total
Hide Arm/Group Description

Combination Therapy (maximum 6 cycles):

  • US commercial cetuximab, manufactured by ImClone, 400 mg/m^2 IV infusion on Day 1 of Cycle 1; subsequently 250 mg/m^2 IV infusion weekly.
  • Cis 100 mg/m^2 or carbo AUC 5, up to a maximum 750 mg dose, IV infusion on Day 1 of every 21-day cycle, 1 hour after cetuximab infusion.
  • 5-FU: 1000 mg/m^2 IV infusion on Days 1 through 4 of every 21-day cycle.

Monotherapy Therapy:

Participants who did not experience disease progression after 6 cycles of combination therapy continued on weekly US commercial cetuximab monotherapy 250 mg/m^2 until disease progression, unacceptable toxicity, or other withdrawal criteria were met.

Combination Therapy (maximum 6 cycles):

  • US commercial cetuximab, manufactured by ImClone, 400 mg/m^2 IV infusion on Day 1 of Cycle 1; subsequently 250 mg/m^2 IV infusion weekly.
  • Cis 100 mg/m^2 or carbo AUC 5, up to a maximum 750 mg dose, IV infusion on Day 1 of every 21-day cycle, 1 hour after cetuximab infusion.
  • 5-FU: 1000 mg/m^2 IV infusion on Days 1 through 4 of every 21-day cycle.

Monotherapy Therapy:

Participants who did not experience disease progression after 6 cycles of combination therapy continued on weekly US commercial cetuximab monotherapy 250 mg/m^2 until disease progression, unacceptable toxicity, or other withdrawal criteria were met.

Combination Therapy (maximum 6 cycles):

  • Cetuximab, manufactured by BI, 400 mg/m^2 IV infusion on Day 1 of Cycle 1; subsequently 250 mg/m^2 IV infusion weekly.
  • Cis 100 mg/m^2 or carbo AUC 5, up to a maximum 750 mg dose, IV infusion on Day 1 of every 21-day cycle, 1 hour after cetuximab infusion.
  • 5-FU: 1000 mg/m^2 IV infusion on Days 1 through 4 of every 21-day cycle.

Monotherapy Therapy:

Participants who did not experience disease progression after 6 cycles of combination therapy continued on weekly BI-manufactured cetuximab monotherapy 250 mg/m^2 until disease progression, unacceptable toxicity, or other withdrawal criteria were met.

Total of all reporting groups
Overall Number of Baseline Participants 33 77 71 181
Hide Baseline Analysis Population Description
Participants who received at least 1 dose of any study drug (cetuximab, cisplatin, carboplatin, or 5-FU).
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 33 participants 77 participants 71 participants 181 participants
62.9  (8.74) 57.1  (10.75) 59.4  (10.49) 59.0  (10.47)
Sex/Gender, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 33 participants 77 participants 71 participants 181 participants
Female 11 9 15 35
Male 22 68 55 145
Unknown or Not Reported 0 0 1 1
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 33 participants 77 participants 71 participants 181 participants
American Indian or Alaska Native 2 16 9 27
Asian 0 1 2 3
Black or African American 2 7 2 11
White 29 53 56 138
More than 1 race 0 0 1 1
Unknown or Not Reported 0 0 1 1
Region of Enrollment   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 33 participants 77 participants 71 participants 181 participants
United States 27 25 28 80
Mexico 1 23 15 39
Canada 5 29 27 61
[1]
Measure Description: Region of enrollment not available for 1 participant in the cetuximab manufactured by BI reporting group; N=70.
Disease Stage at Study Entry  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 33 participants 77 participants 71 participants 181 participants
Locoregional 6 34 32 72
Metastatic 27 43 38 108
Unknown or not reported 0 0 1 1
Karnofsky Performance Status (KPS)   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 33 participants 77 participants 71 participants 181 participants
KPS 70 5 9 7 21
KPS 80 19 28 22 69
KPS 90 5 32 31 68
KPS 100 4 8 11 23
[1]
Measure Description: The KPS rates the performance status and neurological functioning of a participant on a scale from KPS 0 (Dead) to KPS 100 (No complaints; no evidence of disease) in increments of 10. KPS 90 (Able to carry on normal activity; minor signs or symptoms of disease), KPS 80 (Normal activity with effort; some signs or symptoms of disease), and KPS 70 (Cares for self; unable to carry on normal activity or do active work).
1.Primary Outcome
Title Number of Participants Who Had Treatment-Emergent Adverse Events (TEAEs); Data Analysis Cut-Off: September 27, 2013
Hide Description September 27, 2013 is the date when data was last collected for the primary endpoint. Prior to this date, the manufacturing process for the BI-manufactured cetuximab was changed necessitating the need to switch participants to US commercial cetuximab. All other components of their treatment regimen remained unchanged and participants stayed in their original reporting group. Therefore, the number of participants in the BI-manufactured cetuximab treatment arm who had TEAEs includes TEAEs while participants received BI-manufactured and US-commercial cetuximab. Using September 27 cut-off, the analysis of TEAEs is confounded by the switch from BI-manufactured to US commercial cetuximab. TEAEs were defined as serious and other non-serious AEs that occurred or worsened after study treatment (regardless of causality). TEAE information for Safety Lead-In group available in Reported Adverse Events module which is summary of serious and other non-serious AEs regardless of causality.
Time Frame Part 2: Baseline to end of combination therapy (up to 18 weeks)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study drug (cetuximab, cisplatin, carboplatin, or 5-FU) according to the treatment arm to which they were assigned or randomized. Data is confounded for 9 participants in BI-manufactured cetuximab treatment arm who switched to US commercial cetuximab.
Arm/Group Title Part 2: Combination Therapy: Cetuximab (US Commercial) Part 2: Combination Therapy: Cetuximab (Manufactured by BI)
Hide Arm/Group Description:

Combination Therapy (maximum 6 cycles):

  • US commercial cetuximab, manufactured by ImClone, 400 mg/m^2 IV infusion on Day 1 of Cycle 1; subsequently 250 mg/m^2 IV infusion weekly.
  • Cis 100 mg/m^2 or carbo AUC 5, up to a maximum 750 mg dose, IV infusion on Day 1 of every 21-day cycle, 1 hour after cetuximab infusion.
  • 5-FU: 1000 mg/m^2 IV infusion on Days 1 through 4 of every 21-day cycle.

Combination Therapy (maximum 6 cycles):

  • Cetuximab, manufactured by BI, 400 mg/m^2 IV infusion on Day 1 of Cycle 1; subsequently 250 mg/m^2 IV infusion weekly.
  • Cis 100 mg/m^2 or carbo AUC 5, up to a maximum 750 mg dose, IV infusion on Day 1 of every 21-day cycle, 1 hour after cetuximab infusion.
  • 5-FU: 1000 mg/m^2 IV infusion on Days 1 through 4 of every 21-day cycle.
Overall Number of Participants Analyzed 77 71
Measure Type: Number
Unit of Measure: participants
76 68
2.Primary Outcome
Title Number of Participants Who Had TEAEs; Data Analysis Cut-Off: January 23, 2013
Hide Description January 23, 2013 is the date when the first participant in the BI-manufactured cetuximab treatment arm switched to US commercial cetuximab due to changes in the manufacturing process for the BI-manufactured cetuximab necessitating the need to switch participants to US commercial cetuximab. Each participant who switched treatments received at least 2 cycles of BI-manufactured cetuximab before switching. All other components of their treatment regimen remained unchanged. The number of participants who had TEAEs during combination therapy is reported. Using January 23 cut-off, data is un-confounded by lack of BI-manufactured cetuximab. TEAEs were defined as serious and other non-serious adverse events (AEs) that occurred or worsened after study treatment (regardless of causality). TEAE information for Safety Lead-in group available in Reported Adverse Event module which is summary of serious and other non-serious AEs regardless of causality.
Time Frame Part 2: Baseline to end of combination therapy or date first participant switched to US commercial cetuximab (up to 18 weeks)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study drug (cetuximab, cisplatin, carboplatin, or 5-FU) according to the treatment arm to which they were assigned or randomized.
Arm/Group Title Part 2: Combination Therapy: Cetuximab (US Commercial) Part 2: Combination Therapy: Cetuximab (Manufactured by BI),
Hide Arm/Group Description:

Combination Therapy (maximum 6 cycles):

  • US commercial cetuximab, manufactured by ImClone, 400 mg/m^2 IV infusion on Day 1 of Cycle 1; subsequently 250 mg/m^2 IV infusion weekly.
  • Cis 100 mg/m^2 or carbo AUC 5, up to a maximum 750 mg dose, IV infusion on Day 1 of every 21-day cycle, 1 hour after cetuximab infusion.
  • 5-FU: 1000 mg/m^2 IV infusion on Days 1 through 4 of every 21-day cycle.

Combination Therapy (maximum 6 cycles):

  • Cetuximab, manufactured by BI, 400 mg/m^2 IV infusion on Day 1 of Cycle 1; subsequently 250 mg/m^2 IV infusion weekly.
  • Cis 100 mg/m^2 or carbo AUC 5, up to a maximum 750 mg dose, IV infusion on Day 1 of every 21-day cycle, 1 hour after cetuximab infusion.
  • 5-FU: 1000 mg/m^2 IV infusion on Days 1 through 4 of every 21-day cycle.
Overall Number of Participants Analyzed 77 71
Measure Type: Number
Unit of Measure: participants
75 68
3.Secondary Outcome
Title Overall Survival (OS)
Hide Description OS was defined as duration from the date of randomization to the date of death from any cause. For each participant not known to have died as of the 23 October 2014 data cutoff date for the analysis, OS was censored at the date last known to be alive. In addition, any participants on Arm B who was switched from BI-manufactured cetuximab to ImClone-manufactured cetuximab was censored at the time of the switch.
Time Frame Parts 1 and 2: Randomization to Date of Death from any Cause (Up to 36.3 Months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least on dose of study drug. 4 participants were censored in Safety Lead-In, 17 participants were censored in Cetuximab (US Commercial) and 15 in Cetuximab (Manufactured by BI).
Arm/Group Title Part 1: Safety Lead-In (Cetuximab, Cis or Carbo, 5-FU) Part 2: Combination Therapy: Cetuximab (US Commercial) Part 2: Combination Therapy: Cetuximab (Manufactured by BI)
Hide Arm/Group Description:

Combination Therapy (maximum 6 cycles):

  • United States (US) commercial cetuximab, manufactured by ImClone, 400 milligrams per square meter (mg/m^2) intravenous (IV) infusion on Day 1 of Cycle 1; subsequently 250 mg/m^2 IV infusion weekly.
  • Cisplatin (cis) 100 mg/m^2 or carboplatin (carbo) area under the curve (AUC) 5, up to a maximum 750 mg dose, IV infusion on Day 1 of every 21-day cycle, 1 hour after cetuximab infusion.
  • 5-Fluorouracil (5-FU): 1000 mg/m^2 IV infusion on Days 1 through 4 of every 21-day cycle.

Monotherapy Therapy:

Participants who did not experience disease progression after 6 cycles of combination therapy continued on weekly US commercial cetuximab monotherapy 250 mg/m^2 until disease progression, unacceptable toxicity, or other withdrawal criteria were met.

Combination Therapy (maximum 6 cycles):

  • US commercial cetuximab, manufactured by ImClone, 400 mg/m^2 IV infusion on Day 1 of Cycle 1; subsequently 250 mg/m^2 IV infusion weekly.
  • Cis 100 mg/m^2 or carbo AUC 5, up to a maximum 750 mg dose, IV infusion on Day 1 of every 21-day cycle, 1 hour after cetuximab infusion.
  • 5-FU: 1000 mg/m^2 IV infusion on Days 1 through 4 of every 21-day cycle.

Combination Therapy (maximum 6 cycles):

  • Cetuximab, manufactured by Boehringer Ingelheim (BI), 400 mg/m^2 IV infusion on Day 1 of Cycle 1; subsequently 250 mg/m^2 IV infusion weekly.
  • Cis 100 mg/m^2 or carbo AUC 5, up to a maximum 750 mg dose, IV infusion on Day 1 of every 21-day cycle, 1 hour after cetuximab infusion.
  • 5-FU: 1000 mg/m^2 IV infusion on Days 1 through 4 of every 21-day cycle.
Overall Number of Participants Analyzed 33 77 71
Median (95% Confidence Interval)
Unit of Measure: Months
9.13
(6.60 to 10.38)
9.23
(6.90 to 11.80)
9.46
(6.87 to 11.43)
4.Secondary Outcome
Title Progression-Free Survival (PFS)
Hide Description PFS was defined as duration from the date of randomization to the first date of objective progressive disease (PD) or death from any cause. For each participant who was not known to have died or to have had objective PD as of the 23 October 2014 data cutoff date for the analysis, PFS was censored at the date of the participant’s last complete tumor assessment prior to that cutoff date. In addition, any participant in Arm B who was switched from BI-manufactured cetuximab to ImClone-manufactured cetuximab was censored at the time of the switch.
Time Frame Parts 1 and 2: Randomization to Progression of Disease or Death from any Cause (Up to 32.7 Months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of study drug. 7 participants were censored in Safety Lead-In ,12 participants were censored in Cetuximab (US Commercial) and 15 in Cetuximab (Manufactured by BI).
Arm/Group Title Part 1: Safety Lead-In (Cetuximab, Cis or Carbo, 5-FU) Part 2: Combination Therapy: Cetuximab (US Commercial) Part 2: Combination Therapy: Cetuximab (Manufactured by BI)
Hide Arm/Group Description:

Combination Therapy (maximum 6 cycles):

  • United States (US) commercial cetuximab, manufactured by ImClone, 400 milligrams per square meter (mg/m^2) intravenous (IV) infusion on Day 1 of Cycle 1; subsequently 250 mg/m^2 IV infusion weekly.
  • Cisplatin (cis) 100 mg/m^2 or carboplatin (carbo) area under the curve (AUC) 5, up to a maximum 750 mg dose, IV infusion on Day 1 of every 21-day cycle, 1 hour after cetuximab infusion.
  • 5-Fluorouracil (5-FU): 1000 mg/m^2 IV infusion on Days 1 through 4 of every 21-day cycle.

Monotherapy Therapy:

Participants who did not experience disease progression after 6 cycles of combination therapy continued on weekly US commercial cetuximab monotherapy 250 mg/m^2 until disease progression, unacceptable toxicity, or other withdrawal criteria were met.

Combination Therapy (maximum 6 cycles):

  • US commercial cetuximab, manufactured by ImClone, 400 mg/m^2 IV infusion on Day 1 of Cycle 1; subsequently 250 mg/m^2 IV infusion weekly.
  • Cis 100 mg/m^2 or carbo AUC 5, up to a maximum 750 mg dose, IV infusion on Day 1 of every 21-day cycle, 1 hour after cetuximab infusion.
  • 5-FU: 1000 mg/m^2 IV infusion on Days 1 through 4 of every 21-day cycle.

Combination Therapy (maximum 6 cycles):

  • Cetuximab, manufactured by Boehringer Ingelheim (BI), 400 mg/m^2 IV infusion on Day 1 of Cycle 1; subsequently 250 mg/m^2 IV infusion weekly.
  • Cis 100 mg/m^2 or carbo AUC 5, up to a maximum 750 mg dose, IV infusion on Day 1 of every 21-day cycle, 1 hour after cetuximab infusion.
  • 5-FU: 1000 mg/m^2 IV infusion on Days 1 through 4 of every 21-day cycle.
Overall Number of Participants Analyzed 33 77 71
Median (95% Confidence Interval)
Unit of Measure: Months
4.57
(3.22 to 5.32)
4.34
(3.52 to 5.78)
5.59
(4.04 to 6.28)
5.Secondary Outcome
Title Percentage of Participants Having a Confirmed Best Response of Complete Response (CR) or Partial Response (PR) (Overall Response Rate [ORR])
Hide Description Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST, version [v]1.0) criteria. CR was defined as the disappearance of all target lesions. PR was defined as having at least a 30% decrease in sum of longest diameter of target lesions. Percentage of participants with a confirmed CR or PR=(number of participants whose best overall response was CR or PR)/(number of participants treated)*100.
Time Frame Parts 1 and 2: Randomization to Progression of Disease (Up to 32.7 Months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of study drug.
Arm/Group Title Part 1: Safety Lead-In (Cetuximab, Cis or Carbo, 5-FU) Part 2: Combination Therapy: Cetuximab (US Commercial) Part 2: Combination Therapy: Cetuximab (Manufactured by BI)
Hide Arm/Group Description:

Combination Therapy (maximum 6 cycles):

  • United States (US) commercial cetuximab, manufactured by ImClone, 400 milligrams per square meter (mg/m^2) intravenous (IV) infusion on Day 1 of Cycle 1; subsequently 250 mg/m^2 IV infusion weekly.
  • Cisplatin (cis) 100 mg/m^2 or carboplatin (carbo) area under the curve (AUC) 5, up to a maximum 750 mg dose, IV infusion on Day 1 of every 21-day cycle, 1 hour after cetuximab infusion.
  • 5-Fluorouracil (5-FU): 1000 mg/m^2 IV infusion on Days 1 through 4 of every 21-day cycle.

Monotherapy Therapy:

Participants who did not experience disease progression after 6 cycles of combination therapy continued on weekly US commercial cetuximab monotherapy 250 mg/m^2 until disease progression, unacceptable toxicity, or other withdrawal criteria were met.

Combination Therapy (maximum 6 cycles):

  • US commercial cetuximab, manufactured by ImClone, 400 mg/m^2 IV infusion on Day 1 of Cycle 1; subsequently 250 mg/m^2 IV infusion weekly.
  • Cis 100 mg/m^2 or carbo AUC 5, up to a maximum 750 mg dose, IV infusion on Day 1 of every 21-day cycle, 1 hour after cetuximab infusion.
  • 5-FU: 1000 mg/m^2 IV infusion on Days 1 through 4 of every 21-day cycle.

Combination Therapy (maximum 6 cycles):

  • Cetuximab, manufactured by Boehringer Ingelheim (BI), 400 mg/m^2 IV infusion on Day 1 of Cycle 1; subsequently 250 mg/m^2 IV infusion weekly.
  • Cis 100 mg/m^2 or carbo AUC 5, up to a maximum 750 mg dose, IV infusion on Day 1 of every 21-day cycle, 1 hour after cetuximab infusion.
  • 5-FU: 1000 mg/m^2 IV infusion on Days 1 through 4 of every 21-day cycle.
Overall Number of Participants Analyzed 33 77 71
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
24.2
(9.6 to 38.9)
32.5
(22.0 to 42.9)
36.6
(25.4 to 47.8)
6.Secondary Outcome
Title Number of Participants With Anti-Cetuximab Antibodies
Hide Description [Not Specified]
Time Frame Day 1, Week 1 of Cycles 3 and 5 (postbaseline samples were collected prior to infusion).
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study drug and had evaluable data for antibodies.There was no pre-specified analysis plan for trial to report immunogenicity results separately for each arm,as results were intended to be pooled and combined with other cetuximab trials data.Data was pooled for the three arms for cetuximab in this trial.
Arm/Group Title All Participants (Cetuximab)
Hide Arm/Group Description:

United States (US) commercial cetuximab, manufactured by ImClone, 400 milligrams per square meter (mg/m^2) intravenous (IV) infusion on Day 1 of Cycle 1; subsequently 250 mg/m^2 IV infusion weekly.

OR

Cetuximab, manufactured by Boehringer Ingelheim (BI), 400 mg/m^2 IV infusion on Day 1 of Cycle 1; subsequently 250 mg/m^2 IV infusion weekly.

Overall Number of Participants Analyzed 85
Measure Type: Number
Unit of Measure: participants
4
7.Secondary Outcome
Title Percentage of Participants Having a Best Response of CR, PR, or Stable Disease (SD) - Disease Control Rate (DCR)
Hide Description Response was defined using RECIST, v1.0 criteria. CR was defined as the disappearance of all target lesions. PR was defined as having at least a 30% decrease in sum of longest diameter of target lesions. Progressive Disease (PD) was defined as having at least a 20% increase in the sum of the longest diameter of target lesions. Stable Disease (SD) was defined as small changes that did not meet the above criteria.
Time Frame Parts 1 and 2: Randomization to Progression of Disease (Up to 32.7 Months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of study drug.
Arm/Group Title Part 1: Safety Lead-In (Cetuximab, Cis or Carbo, 5-FU) Part 2: Combination Therapy: Cetuximab (US Commercial) Part 2: Combination Therapy: Cetuximab (Manufactured by BI)
Hide Arm/Group Description:

Combination Therapy (maximum 6 cycles):

  • United States (US) commercial cetuximab, manufactured by ImClone, 400 milligrams per square meter (mg/m^2) intravenous (IV) infusion on Day 1 of Cycle 1; subsequently 250 mg/m^2 IV infusion weekly.
  • Cisplatin (cis) 100 mg/m^2 or carboplatin (carbo) area under the curve (AUC) 5, up to a maximum 750 mg dose, IV infusion on Day 1 of every 21-day cycle, 1 hour after cetuximab infusion.
  • 5-Fluorouracil (5-FU): 1000 mg/m^2 IV infusion on Days 1 through 4 of every 21-day cycle.

Monotherapy Therapy:

Participants who did not experience disease progression after 6 cycles of combination therapy continued on weekly US commercial cetuximab monotherapy 250 mg/m^2 until disease progression, unacceptable toxicity, or other withdrawal criteria were met.

Combination Therapy (maximum 6 cycles):

  • US commercial cetuximab, manufactured by ImClone, 400 mg/m^2 IV infusion on Day 1 of Cycle 1; subsequently 250 mg/m^2 IV infusion weekly.
  • Cis 100 mg/m^2 or carbo AUC 5, up to a maximum 750 mg dose, IV infusion on Day 1 of every 21-day cycle, 1 hour after cetuximab infusion.
  • 5-FU: 1000 mg/m^2 IV infusion on Days 1 through 4 of every 21-day cycle.

Combination Therapy (maximum 6 cycles):

  • Cetuximab, manufactured by Boehringer Ingelheim (BI), 400 mg/m^2 IV infusion on Day 1 of Cycle 1; subsequently 250 mg/m^2 IV infusion weekly.
  • Cis 100 mg/m^2 or carbo AUC 5, up to a maximum 750 mg dose, IV infusion on Day 1 of every 21-day cycle, 1 hour after cetuximab infusion.
  • 5-FU: 1000 mg/m^2 IV infusion on Days 1 through 4 of every 21-day cycle.
Overall Number of Participants Analyzed 33 77 71
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
69.7
(54.0 to 85.4)
58.4
(47.4 to 69.4)
62.0
(50.7 to 73.3)
8.Secondary Outcome
Title Maximum Serum Concentration (Cmax) of Cetuximab Following 400 mg/m² Cetuximab Dosing
Hide Description The Cmax of cetuximab following 400 mg/m² cetuximab dosing during Part 2 of the study is reported. As specified in the protocol, pharmacokinetics (PK) samples were not collected during Part 1 of the study, Safety Lead-In or during Part 2 monotherapy.
Time Frame Part 2: Cycle 1, Day 1: 0 hours [(h); immediately postdose], 1 h, 2 h, and 24 h postdose
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of cetuximab (400 mg/m²) and had valid serum cetuximab concentrations during the specified time frame. No participant was analyzed during Part 1 of the study, Safety Lead-In or during Part 2 monotherapy..
Arm/Group Title Part 2: Combination Therapy: Cetuximab (US Commercial) Part 2: Combination Therapy: Cetuximab (Manufactured by BI)
Hide Arm/Group Description:

Combination Therapy (maximum 6 cycles):

  • US commercial cetuximab, manufactured by ImClone, 400 mg/m^2 IV infusion on Day 1 of Cycle 1; subsequently 250 mg/m^2 IV infusion weekly.
  • Cis 100 mg/m^2 or carbo AUC 5, up to a maximum 750 mg dose, IV infusion on Day 1 of every 21-day cycle, 1 hour after cetuximab infusion.
  • 5-FU: 1000 mg/m^2 IV infusion on Days 1 through 4 of every 21-day cycle.

Combination Therapy (maximum 6 cycles):

  • Cetuximab, manufactured by BI, 400 mg/m^2 IV infusion on Day 1 of Cycle 1; subsequently 250 mg/m^2 IV infusion weekly.
  • Cis 100 mg/m^2 or carbo AUC 5, up to a maximum 750 mg dose, IV infusion on Day 1 of every 21-day cycle, 1 hour after cetuximab infusion.
  • 5-FU: 1000 mg/m^2 IV infusion on Days 1 through 4 of every 21-day cycle.
Overall Number of Participants Analyzed 61 53
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: micrograms per milliliter (μg/mL)
208
(10.2%)
208
(7.8%)
9.Secondary Outcome
Title Cmax of Cetuximab at Steady State
Hide Description A total of 4 samples were collected at various times during combination therapy, from the third dose of 250 mg/m^2 cetuximab in Cycle 1 (Week 3) through the final dose in Cycle 3 (Week 3) and used to report Cmax of cetuximab at steady state during Part 2 of the study. As specified in the protocol, PK samples were not collected during Part 1 of the study, Safety Lead-In, or during Part 2 monotherapy.
Time Frame Part 2: Weekly from Cycle 1, Week 3 through Cycle 3, Week 3: 0 h (immediately postdose), 24 h, 96 h, and 168 h postdose
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of cetuximab (400 mg/m^2) and had valid serum cetuximab concentrations during the specified time frame. No participant was analyzed during Part 1 of the study, Safety Lead-In, or during Part 2 monotherapy.
Arm/Group Title Part 2: Combination Therapy: Cetuximab (US Commercial) Part 2: Combination Therapy: Cetuximab (Manufactured by BI)
Hide Arm/Group Description:

Combination Therapy (maximum 6 cycles):

  • US commercial cetuximab, manufactured by ImClone, 400 mg/m^2 IV infusion on Day 1 of Cycle 1; subsequently 250 mg/m^2 IV infusion weekly.
  • Cis 100 mg/m^2 or carbo AUC 5, up to a maximum 750 mg dose, IV infusion on Day 1 of every 21-day cycle, 1 hour after cetuximab infusion.
  • 5-FU: 1000 mg/m^2 IV infusion on Days 1 through 4 of every 21-day cycle.

Combination Therapy (maximum 6 cycles):

  • Cetuximab, manufactured by Boehringer Ingelheim (BI), 400 mg/m^2 IV infusion on Day 1 of Cycle 1; subsequently 250 mg/m^2 IV infusion weekly.
  • Cis 100 mg/m^2 or carbo AUC 5, up to a maximum 750 mg dose, IV infusion on Day 1 of every 21-day cycle, 1 hour after cetuximab infusion.
  • 5-FU: 1000 mg/m^2 IV infusion on Days 1 through 4 of every 21-day cycle.
Overall Number of Participants Analyzed 44 46
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: micrograms per milliliter (μg/mL)
225
(17.7%)
199
(15.3%)
10.Secondary Outcome
Title Area Under the Concentration Curve (AUC) of Cetuximab at Steady State
Hide Description A total of 4 samples were collected during combination therapy, from the first dose of 250 mg/m^2 cetuximab in Cycle 1 (Day 1) through the final dose in Cycle 3 (Week 3) and used to report AUC of cetuximab at steady state during Part 2 of the study. As specified in the protocol, PK samples were not collected during Part 1 of the study, Safety Lead-In, or during Part 2 monotherapy.
Time Frame Part 2: Weekly from Cycle 1, Day 1 through Cycle 3, Week 3: 0 h (immediately postdose), 24 h, 96 h, and 168 h postdose
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of cetuximab (250 mg/m^2) and had valid serum cetuximab concentrations during the specified time frame. No participant was analyzed during Part 1 of the study, Safety Lead-In, or during Part 2 monotherapy.
Arm/Group Title Part 2: Combination Therapy: Cetuximab (US Commercial) Part 2: Combination Therapy: Cetuximab (Manufactured by BI)
Hide Arm/Group Description:

Combination Therapy (maximum 6 cycles):

  • US commercial cetuximab, manufactured by ImClone, 400 mg/m^2 IV infusion on Day 1 of Cycle 1; subsequently 250 mg/m^2 IV infusion weekly.
  • Cis 100 mg/m^2 or carbo AUC 5, up to a maximum 750 mg dose, IV infusion on Day 1 of every 21-day cycle, 1 hour after cetuximab infusion.
  • 5-FU: 1000 mg/m^2 IV infusion on Days 1 through 4 of every 21-day cycle.

Combination Therapy (maximum 6 cycles):

  • Cetuximab, manufactured by BI, 400 mg/m^2 IV infusion on Day 1 of Cycle 1; subsequently 250 mg/m^2 IV infusion weekly.
  • Cis 100 mg/m^2 or carbo AUC 5, up to a maximum 750 mg dose, IV infusion on Day 1 of every 21-day cycle, 1 hour after cetuximab infusion.
  • 5-FU: 1000 mg/m^2 IV infusion on Days 1 through 4 of every 21-day cycle.
Overall Number of Participants Analyzed 61 55
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: micrograms*hours/milliliter (μg*h/mL)
21900
(31.8%)
18800
(25.5%)
Time Frame [Not Specified]
Adverse Event Reporting Description Serious adverse events (SAEs) and other non-serious AEs are reported for participants who received at least 1 dose of any drug (cetuximab, cisplatin, carboplatin, or 5-FU). Death due to progressive disease was not considered an AE.
 
Arm/Group Title Part 1: Safety Lead-In (Cetuximab, Cis or Carbo, 5-FU) Part 2: Cetuximab (US Commercial), Cis or Carbo, 5-FU Part 2: Cetuximab (Manufactured by BI), Cis or Carbo, 5-FU
Hide Arm/Group Description

Combination Therapy (maximum 6 cycles):

  • US commercial cetuximab, manufactured by ImClone, 400 mg/m^2 IV infusion on Day 1 of Cycle 1; subsequently 250 mg/m^2 IV infusion weekly.
  • Cis 100 mg/m^2 or carbo AUC 5, up to a maximum 750 mg dose, IV infusion on Day 1 of every 21-day cycle, 1 hour after cetuximab infusion.
  • 5-FU: 1000 mg/m^2 IV infusion on Days 1 through 4 of every 21-day cycle.

Monotherapy Therapy:

Participants who did not experience disease progression after 6 cycles of combination therapy continued on weekly US commercial cetuximab monotherapy 250 mg/m^2 until disease progression, unacceptable toxicity, or other withdrawal criteria were met.

Combination Therapy (maximum 6 cycles):

  • US commercial cetuximab, manufactured by ImClone, 400 mg/m^2 IV infusion on Day 1 of Cycle 1; subsequently 250 mg/m^2 IV infusion weekly.
  • Cis 100 mg/m^2 or carbo AUC 5, up to a maximum 750 mg dose, IV infusion on Day 1 of every 21-day cycle, 1 hour after cetuximab infusion.
  • 5-FU: 1000 mg/m^2 IV infusion on Days 1 through 4 of every 21-day cycle.

Monotherapy Therapy:

Participants who did not experience disease progression after 6 cycles of combination therapy continued on weekly US commercial cetuximab monotherapy 250 mg/m^2 until disease progression, unacceptable toxicity, or other withdrawal criteria were met.

Combination Therapy (maximum 6 cycles):

  • Cetuximab, manufactured by BI, 400 mg/m^2 IV infusion on Day 1 of Cycle 1; subsequently 250 mg/m^2 IV infusion weekly.
  • Cis 100 mg/m^2 or carbo AUC 5, up to a maximum 750 mg dose, IV infusion on Day 1 of every 21-day cycle, 1 hour after cetuximab infusion.
  • 5-FU: 1000 mg/m^2 IV infusion on Days 1 through 4 of every 21-day cycle.

Monotherapy Therapy:

Participants who did not experience disease progression after 6 cycles of combination therapy continued on weekly BI-manufactured cetuximab monotherapy 250 mg/m^2 until disease progression, unacceptable toxicity, or other withdrawal criteria were met.

All-Cause Mortality
Part 1: Safety Lead-In (Cetuximab, Cis or Carbo, 5-FU) Part 2: Cetuximab (US Commercial), Cis or Carbo, 5-FU Part 2: Cetuximab (Manufactured by BI), Cis or Carbo, 5-FU
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Part 1: Safety Lead-In (Cetuximab, Cis or Carbo, 5-FU) Part 2: Cetuximab (US Commercial), Cis or Carbo, 5-FU Part 2: Cetuximab (Manufactured by BI), Cis or Carbo, 5-FU
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   20/33 (60.61%)      48/77 (62.34%)      42/71 (59.15%)    
Blood and lymphatic system disorders       
Anaemia  1  4/33 (12.12%)  6 4/77 (5.19%)  8 5/71 (7.04%)  6
Febrile neutropenia  1  2/33 (6.06%)  2 1/77 (1.30%)  2 5/71 (7.04%)  5
Leukocytosis  1  0/33 (0.00%)  0 1/77 (1.30%)  1 0/71 (0.00%)  0
Leukopenia  1  2/33 (6.06%)  3 1/77 (1.30%)  5 0/71 (0.00%)  0
Neutropenia  1  2/33 (6.06%)  4 6/77 (7.79%)  9 3/71 (4.23%)  3
Thrombocytopenia  1  1/33 (3.03%)  2 2/77 (2.60%)  2 2/71 (2.82%)  3
Cardiac disorders       
Atrial fibrillation  1  0/33 (0.00%)  0 0/77 (0.00%)  0 1/71 (1.41%)  1
Cardiac arrest  1  0/33 (0.00%)  0 2/77 (2.60%)  3 1/71 (1.41%)  1
Myocardial infarction  1  0/33 (0.00%)  0 0/77 (0.00%)  0 1/71 (1.41%)  1
Ventricular tachycardia  1  0/33 (0.00%)  0 0/77 (0.00%)  0 1/71 (1.41%)  1
Gastrointestinal disorders       
Abdominal pain  1  1/33 (3.03%)  1 0/77 (0.00%)  0 0/71 (0.00%)  0
Constipation  1  0/33 (0.00%)  0 2/77 (2.60%)  2 0/71 (0.00%)  0
Diarrhoea  1  6/33 (18.18%)  7 3/77 (3.90%)  5 2/71 (2.82%)  5
Duodenal perforation  1  0/33 (0.00%)  0 0/77 (0.00%)  0 1/71 (1.41%)  2
Dysphagia  1  1/33 (3.03%)  1 1/77 (1.30%)  1 2/71 (2.82%)  2
Ileus  1  0/33 (0.00%)  0 1/77 (1.30%)  2 0/71 (0.00%)  0
Intestinal ischaemia  1  1/33 (3.03%)  2 0/77 (0.00%)  0 1/71 (1.41%)  1
Intestinal obstruction  1  0/33 (0.00%)  0 1/77 (1.30%)  1 0/71 (0.00%)  0
Nausea  1  4/33 (12.12%)  4 7/77 (9.09%)  10 2/71 (2.82%)  2
Pneumatosis intestinalis  1  1/33 (3.03%)  1 0/77 (0.00%)  0 1/71 (1.41%)  2
Pneumoperitoneum  1  0/33 (0.00%)  0 1/77 (1.30%)  1 0/71 (0.00%)  0
Small intestinal obstruction  1  1/33 (3.03%)  1 0/77 (0.00%)  0 0/71 (0.00%)  0
Upper gastrointestinal haemorrhage  1  1/33 (3.03%)  1 0/77 (0.00%)  0 2/71 (2.82%)  3
Vomiting  1  4/33 (12.12%)  4 7/77 (9.09%)  10 4/71 (5.63%)  7
General disorders       
Asthenia  1  1/33 (3.03%)  1 1/77 (1.30%)  1 0/71 (0.00%)  0
Death  1  0/33 (0.00%)  0 1/77 (1.30%)  1 0/71 (0.00%)  0
Fatigue  1  3/33 (9.09%)  10 1/77 (1.30%)  1 1/71 (1.41%)  2
General physical health deterioration  1  0/33 (0.00%)  0 1/77 (1.30%)  1 0/71 (0.00%)  0
Medical device complication  1  0/33 (0.00%)  0 1/77 (1.30%)  1 0/71 (0.00%)  0
Mucosal inflammation  1  1/33 (3.03%)  1 4/77 (5.19%)  5 1/71 (1.41%)  1
Multi-organ failure  1  0/33 (0.00%)  0 0/77 (0.00%)  0 1/71 (1.41%)  1
Pain  1  0/33 (0.00%)  0 0/77 (0.00%)  0 1/71 (1.41%)  1
Pyrexia  1  1/33 (3.03%)  1 1/77 (1.30%)  1 1/71 (1.41%)  1
Thrombosis in device  1  0/33 (0.00%)  0 1/77 (1.30%)  1 0/71 (0.00%)  0
Hepatobiliary disorders       
Cholecystitis  1  0/33 (0.00%)  0 0/77 (0.00%)  0 1/71 (1.41%)  2
Cholelithiasis  1  0/33 (0.00%)  0 0/77 (0.00%)  0 1/71 (1.41%)  1
Hydrocholecystis  1  0/33 (0.00%)  0 0/77 (0.00%)  0 1/71 (1.41%)  1
Immune system disorders       
Anaphylactic reaction  1  2/33 (6.06%)  3 0/77 (0.00%)  0 0/71 (0.00%)  0
Anaphylactic shock  1  0/33 (0.00%)  0 3/77 (3.90%)  3 0/71 (0.00%)  0
Drug hypersensitivity  1  1/33 (3.03%)  1 0/77 (0.00%)  0 0/71 (0.00%)  0
Hypersensitivity  1  1/33 (3.03%)  1 0/77 (0.00%)  0 0/71 (0.00%)  0
Infections and infestations       
Abdominal abscess  1  0/33 (0.00%)  0 0/77 (0.00%)  0 1/71 (1.41%)  3
Bacterial infection  1  0/33 (0.00%)  0 0/77 (0.00%)  0 1/71 (1.41%)  1
Bacterial sepsis  1  0/33 (0.00%)  0 1/77 (1.30%)  1 0/71 (0.00%)  0
Clostridium difficile colitis  1  0/33 (0.00%)  0 0/77 (0.00%)  0 1/71 (1.41%)  2
Device related infection  1  2/33 (6.06%)  2 2/77 (2.60%)  2 2/71 (2.82%)  4
Infectious pleural effusion  1  0/33 (0.00%)  0 1/77 (1.30%)  2 0/71 (0.00%)  0
Intervertebral discitis  1  0/33 (0.00%)  0 1/77 (1.30%)  1 0/71 (0.00%)  0
Joint abscess  1  0/33 (0.00%)  0 0/77 (0.00%)  0 1/71 (1.41%)  1
Oral infection  1  0/33 (0.00%)  0 0/77 (0.00%)  0 1/71 (1.41%)  1
Pneumonia  1  3/33 (9.09%)  6 5/77 (6.49%)  9 5/71 (7.04%)  6
Sepsis  1  3/33 (9.09%)  3 5/77 (6.49%)  5 1/71 (1.41%)  2
Septic shock  1  0/33 (0.00%)  0 2/77 (2.60%)  2 4/71 (5.63%)  6
Urinary tract infection  1  0/33 (0.00%)  0 1/77 (1.30%)  1 0/71 (0.00%)  0
Injury, poisoning and procedural complications       
Arterial injury  1  0/33 (0.00%)  0 0/77 (0.00%)  0 1/71 (1.41%)  1
Carbon monoxide poisoning  1  0/33 (0.00%)  0 0/77 (0.00%)  0 1/71 (1.41%)  1
Fall  1  1/33 (3.03%)  1 0/77 (0.00%)  0 0/71 (0.00%)  0
Infusion related reaction  1  0/33 (0.00%)  0 1/77 (1.30%)  1 0/71 (0.00%)  0
Post procedural haemorrhage  1  0/33 (0.00%)  0 2/77 (2.60%)  4 0/71 (0.00%)  0
Tracheal obstruction  1  1/33 (3.03%)  1 0/77 (0.00%)  0 1/71 (1.41%)  1
Vena cava injury  1  0/33 (0.00%)  0 1/77 (1.30%)  1 0/71 (0.00%)  0
Investigations       
Activated partial thromboplastin time prolonged  1  1/33 (3.03%)  2 0/77 (0.00%)  0 0/71 (0.00%)  0
Blood bilirubin increased  1  1/33 (3.03%)  1 0/77 (0.00%)  0 0/71 (0.00%)  0
International normalised ratio increased  1  1/33 (3.03%)  2 0/77 (0.00%)  0 0/71 (0.00%)  0
Lymphocyte count decreased  1  0/33 (0.00%)  0 0/77 (0.00%)  0 1/71 (1.41%)  1
Neutrophil count decreased  1  2/33 (6.06%)  4 1/77 (1.30%)  3 1/71 (1.41%)  1
Platelet count decreased  1  2/33 (6.06%)  3 0/77 (0.00%)  0 2/71 (2.82%)  2
White blood cell count decreased  1  1/33 (3.03%)  1 1/77 (1.30%)  3 1/71 (1.41%)  1
Metabolism and nutrition disorders       
Decreased appetite  1  2/33 (6.06%)  2 1/77 (1.30%)  1 1/71 (1.41%)  1
Dehydration  1  5/33 (15.15%)  8 7/77 (9.09%)  10 9/71 (12.68%)  11
Fluid intake reduced  1  0/33 (0.00%)  0 0/77 (0.00%)  0 1/71 (1.41%)  1
Hypercalcaemia  1  0/33 (0.00%)  0 1/77 (1.30%)  1 1/71 (1.41%)  1
Hypoalbuminaemia  1  1/33 (3.03%)  1 0/77 (0.00%)  0 0/71 (0.00%)  0
Hypocalcaemia  1  1/33 (3.03%)  1 0/77 (0.00%)  0 0/71 (0.00%)  0
Hypoglycaemia  1  0/33 (0.00%)  0 0/77 (0.00%)  0 1/71 (1.41%)  2
Hypokalaemia  1  2/33 (6.06%)  2 4/77 (5.19%)  6 1/71 (1.41%)  1
Hypomagnesaemia  1  1/33 (3.03%)  1 2/77 (2.60%)  4 1/71 (1.41%)  1
Hyponatraemia  1  1/33 (3.03%)  1 4/77 (5.19%)  6 3/71 (4.23%)  6
Hypophosphataemia  1  0/33 (0.00%)  0 1/77 (1.30%)  1 0/71 (0.00%)  0
Malnutrition  1  2/33 (6.06%)  2 0/77 (0.00%)  0 0/71 (0.00%)  0
Tumour lysis syndrome  1  0/33 (0.00%)  0 1/77 (1.30%)  1 0/71 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Metastases to meninges  1  0/33 (0.00%)  0 1/77 (1.30%)  4 0/71 (0.00%)  0
Pericardial effusion malignant  1  0/33 (0.00%)  0 1/77 (1.30%)  1 0/71 (0.00%)  0
Tumour necrosis  1  0/33 (0.00%)  0 1/77 (1.30%)  2 0/71 (0.00%)  0
Tumour pain  1  0/33 (0.00%)  0 1/77 (1.30%)  2 0/71 (0.00%)  0
Nervous system disorders       
Cerebral infarction  1  0/33 (0.00%)  0 1/77 (1.30%)  3 0/71 (0.00%)  0
Cerebrovascular accident  1  0/33 (0.00%)  0 1/77 (1.30%)  1 1/71 (1.41%)  1
Cognitive disorder  1  1/33 (3.03%)  1 0/77 (0.00%)  0 0/71 (0.00%)  0
Depressed level of consciousness  1  1/33 (3.03%)  1 0/77 (0.00%)  0 0/71 (0.00%)  0
Haemorrhage intracranial  1  0/33 (0.00%)  0 1/77 (1.30%)  1 0/71 (0.00%)  0
Ischaemic stroke  1  0/33 (0.00%)  0 2/77 (2.60%)  3 0/71 (0.00%)  0
Syncope  1  0/33 (0.00%)  0 1/77 (1.30%)  1 0/71 (0.00%)  0
Psychiatric disorders       
Panic attack  1  0/33 (0.00%)  0 0/77 (0.00%)  0 1/71 (1.41%)  1
Renal and urinary disorders       
Renal failure  1  0/33 (0.00%)  0 0/77 (0.00%)  0 3/71 (4.23%)  30
Renal failure acute  1  0/33 (0.00%)  0 3/77 (3.90%)  5 2/71 (2.82%)  4
Renal impairment  1  0/33 (0.00%)  0 0/77 (0.00%)  0 1/71 (1.41%)  1
Urinary tract obstruction  1  1/33 (3.03%)  1 0/77 (0.00%)  0 0/71 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Acute respiratory failure  1  0/33 (0.00%)  0 0/77 (0.00%)  0 2/71 (2.82%)  2
Aspiration  1  0/33 (0.00%)  0 1/77 (1.30%)  1 0/71 (0.00%)  0
Dyspnoea  1  0/33 (0.00%)  0 1/77 (1.30%)  1 2/71 (2.82%)  2
Epistaxis  1  1/33 (3.03%)  2 0/77 (0.00%)  0 0/71 (0.00%)  0
Haemoptysis  1  0/33 (0.00%)  0 0/77 (0.00%)  0 1/71 (1.41%)  1
Hydropneumothorax  1  0/33 (0.00%)  0 0/77 (0.00%)  0 1/71 (1.41%)  1
Hypoxia  1  1/33 (3.03%)  1 0/77 (0.00%)  0 1/71 (1.41%)  2
Laryngeal haemorrhage  1  0/33 (0.00%)  0 0/77 (0.00%)  0 1/71 (1.41%)  1
Obstructive airways disorder  1  0/33 (0.00%)  0 1/77 (1.30%)  1 0/71 (0.00%)  0
Pleural effusion  1  1/33 (3.03%)  1 2/77 (2.60%)  3 1/71 (1.41%)  2
Pneumonia aspiration  1  0/33 (0.00%)  0 2/77 (2.60%)  3 1/71 (1.41%)  1
Pneumothorax  1  0/33 (0.00%)  0 1/77 (1.30%)  1 0/71 (0.00%)  0
Productive cough  1  1/33 (3.03%)  1 0/77 (0.00%)  0 0/71 (0.00%)  0
Pulmonary embolism  1  1/33 (3.03%)  5 0/77 (0.00%)  0 3/71 (4.23%)  9
Respiratory distress  1  0/33 (0.00%)  0 0/77 (0.00%)  0 1/71 (1.41%)  2
Respiratory failure  1  0/33 (0.00%)  0 3/77 (3.90%)  3 1/71 (1.41%)  1
Skin and subcutaneous tissue disorders       
Decubitus ulcer  1  1/33 (3.03%)  1 0/77 (0.00%)  0 0/71 (0.00%)  0
Dermatitis acneiform  1  1/33 (3.03%)  1 0/77 (0.00%)  0 0/71 (0.00%)  0
Palmar-plantar erythrodysaesthesia syndrome  1  0/33 (0.00%)  0 0/77 (0.00%)  0 1/71 (1.41%)  1
Rash  1  0/33 (0.00%)  0 0/77 (0.00%)  0 1/71 (1.41%)  3
Vascular disorders       
Deep vein thrombosis  1  0/33 (0.00%)  0 1/77 (1.30%)  5 1/71 (1.41%)  3
Embolism  1  2/33 (6.06%)  3 0/77 (0.00%)  0 0/71 (0.00%)  0
Haemorrhage  1  0/33 (0.00%)  0 0/77 (0.00%)  0 1/71 (1.41%)  1
Hypotension  1  1/33 (3.03%)  1 1/77 (1.30%)  1 2/71 (2.82%)  2
Hypovolaemic shock  1  0/33 (0.00%)  0 1/77 (1.30%)  1 1/71 (1.41%)  1
Shock haemorrhagic  1  0/33 (0.00%)  0 0/77 (0.00%)  0 1/71 (1.41%)  1
Thrombosis  1  1/33 (3.03%)  8 0/77 (0.00%)  0 2/71 (2.82%)  3
Vena cava thrombosis  1  0/33 (0.00%)  0 1/77 (1.30%)  1 0/71 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Part 1: Safety Lead-In (Cetuximab, Cis or Carbo, 5-FU) Part 2: Cetuximab (US Commercial), Cis or Carbo, 5-FU Part 2: Cetuximab (Manufactured by BI), Cis or Carbo, 5-FU
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   32/33 (96.97%)      64/77 (83.12%)      62/71 (87.32%)    
Blood and lymphatic system disorders       
Anaemia  1  18/33 (54.55%)  86 19/77 (24.68%)  103 27/71 (38.03%)  138
Febrile neutropenia  1  0/33 (0.00%)  0 0/77 (0.00%)  0 6/71 (8.45%)  17
Leukopenia  1  3/33 (9.09%)  8 4/77 (5.19%)  19 4/71 (5.63%)  13
Neutropenia  1  15/33 (45.45%)  60 17/77 (22.08%)  30 23/71 (32.39%)  64
Thrombocytopenia  1  8/33 (24.24%)  35 6/77 (7.79%)  8 10/71 (14.08%)  39
Cardiac disorders       
Sinus tachycardia  1  0/33 (0.00%)  0 0/77 (0.00%)  0 5/71 (7.04%)  18
Ear and labyrinth disorders       
Ear pain  1  3/33 (9.09%)  14 0/77 (0.00%)  0 0/71 (0.00%)  0
Tinnitus  1  2/33 (6.06%)  2 6/77 (7.79%)  68 8/71 (11.27%)  62
Eye disorders       
Eye pruritus  1  3/33 (9.09%)  8 0/77 (0.00%)  0 0/71 (0.00%)  0
Vision blurred  1  0/33 (0.00%)  0 0/77 (0.00%)  0 4/71 (5.63%)  13
Gastrointestinal disorders       
Abdominal pain  1  4/33 (12.12%)  12 6/77 (7.79%)  18 6/71 (8.45%)  19
Constipation  1  9/33 (27.27%)  31 16/77 (20.78%)  48 25/71 (35.21%)  112
Diarrhoea  1  15/33 (45.45%)  39 23/77 (29.87%)  47 22/71 (30.99%)  49
Dry mouth  1  2/33 (6.06%)  15 0/77 (0.00%)  0 0/71 (0.00%)  0
Dyspepsia  1  0/33 (0.00%)  0 5/77 (6.49%)  28 8/71 (11.27%)  25
Dysphagia  1  0/33 (0.00%)  0 0/77 (0.00%)  0 6/71 (8.45%)  24
Gastrooesophageal reflux disease  1  4/33 (12.12%)  28 7/77 (9.09%)  32 7/71 (9.86%)  57
Glossodynia  1  2/33 (6.06%)  4 0/77 (0.00%)  0 0/71 (0.00%)  0
Nausea  1  19/33 (57.58%)  88 34/77 (44.16%)  109 33/71 (46.48%)  102
Oral pain  1  0/33 (0.00%)  0 5/77 (6.49%)  21 0/71 (0.00%)  0
Stomatitis  1  9/33 (27.27%)  36 21/77 (27.27%)  96 22/71 (30.99%)  114
Vomiting  1  15/33 (45.45%)  35 17/77 (22.08%)  44 25/71 (35.21%)  82
General disorders       
Asthenia  1  2/33 (6.06%)  3 8/77 (10.39%)  49 4/71 (5.63%)  15
Chest pain  1  2/33 (6.06%)  3 0/77 (0.00%)  0 0/71 (0.00%)  0
Chills  1  3/33 (9.09%)  3 0/77 (0.00%)  0 0/71 (0.00%)  0
Fatigue  1  16/33 (48.48%)  91 35/77 (45.45%)  204 37/71 (52.11%)  221
Mucosal inflammation  1  5/33 (15.15%)  24 12/77 (15.58%)  41 16/71 (22.54%)  83
Oedema peripheral  1  3/33 (9.09%)  5 0/77 (0.00%)  0 5/71 (7.04%)  18
Pain  1  0/33 (0.00%)  0 5/77 (6.49%)  14 4/71 (5.63%)  12
Pyrexia  1  5/33 (15.15%)  9 8/77 (10.39%)  10 8/71 (11.27%)  9
Infections and infestations       
Candida infection  1  0/33 (0.00%)  0 0/77 (0.00%)  0 4/71 (5.63%)  10
Nasopharyngitis  1  0/33 (0.00%)  0 4/77 (5.19%)  8 0/71 (0.00%)  0
Paronychia  1  2/33 (6.06%)  5 9/77 (11.69%)  74 10/71 (14.08%)  63
Skin infection  1  0/33 (0.00%)  0 0/77 (0.00%)  0 5/71 (7.04%)  14
Upper respiratory tract infection  1  2/33 (6.06%)  9 0/77 (0.00%)  0 0/71 (0.00%)  0
Urinary tract infection  1  3/33 (9.09%)  6 0/77 (0.00%)  0 0/71 (0.00%)  0
Vulvovaginal mycotic infection  1  1/11 (9.09%)  1 0/77 (0.00%)  0 0/71 (0.00%)  0
Injury, poisoning and procedural complications       
Fall  1  2/33 (6.06%)  2 0/77 (0.00%)  0 0/71 (0.00%)  0
Investigations       
Blood alkaline phosphatase increased  1  3/33 (9.09%)  14 0/77 (0.00%)  0 0/71 (0.00%)  0
Blood creatinine increased  1  7/33 (21.21%)  9 0/77 (0.00%)  0 0/71 (0.00%)  0
International normalised ratio increased  1  2/33 (6.06%)  4 0/77 (0.00%)  0 0/71 (0.00%)  0
Lymphocyte count decreased  1  3/33 (9.09%)  15 0/77 (0.00%)  0 0/71 (0.00%)  0
Neutrophil count decreased  1  6/33 (18.18%)  22 11/77 (14.29%)  26 14/71 (19.72%)  35
Platelet count decreased  1  5/33 (15.15%)  14 11/77 (14.29%)  51 10/71 (14.08%)  48
Weight decreased  1  7/33 (21.21%)  34 10/77 (12.99%)  58 14/71 (19.72%)  65
White blood cell count decreased  1  6/33 (18.18%)  15 0/77 (0.00%)  0 4/71 (5.63%)  9
Metabolism and nutrition disorders       
Decreased appetite  1  6/33 (18.18%)  26 15/77 (19.48%)  70 21/71 (29.58%)  69
Dehydration  1  8/33 (24.24%)  17 8/77 (10.39%)  12 12/71 (16.90%)  23
Hypercalcaemia  1  3/33 (9.09%)  5 0/77 (0.00%)  0 0/71 (0.00%)  0
Hyperglycaemia  1  3/33 (9.09%)  23 4/77 (5.19%)  9 0/71 (0.00%)  0
Hyperkalaemia  1  2/33 (6.06%)  4 0/77 (0.00%)  0 0/71 (0.00%)  0
Hypernatraemia  1  2/33 (6.06%)  3 0/77 (0.00%)  0 0/71 (0.00%)  0
Hypoalbuminaemia  1  8/33 (24.24%)  24 0/77 (0.00%)  0 0/71 (0.00%)  0
Hypocalcaemia  1  6/33 (18.18%)  17 4/77 (5.19%)  25 7/71 (9.86%)  22
Hypokalaemia  1  14/33 (42.42%)  31 17/77 (22.08%)  69 23/71 (32.39%)  82
Hypomagnesaemia  1  18/33 (54.55%)  73 30/77 (38.96%)  237 29/71 (40.85%)  161
Hyponatraemia  1  4/33 (12.12%)  10 0/77 (0.00%)  0 10/71 (14.08%)  38
Hypophosphataemia  1  2/33 (6.06%)  2 4/77 (5.19%)  11 8/71 (11.27%)  25
Musculoskeletal and connective tissue disorders       
Arthralgia  1  0/33 (0.00%)  0 4/77 (5.19%)  31 0/71 (0.00%)  0
Back pain  1  3/33 (9.09%)  13 5/77 (6.49%)  9 4/71 (5.63%)  12
Muscular weakness  1  0/33 (0.00%)  0 0/77 (0.00%)  0 9/71 (12.68%)  41
Pain in extremity  1  0/33 (0.00%)  0 5/77 (6.49%)  13 5/71 (7.04%)  25
Nervous system disorders       
Dizziness  1  3/33 (9.09%)  16 9/77 (11.69%)  43 11/71 (15.49%)  29
Dysgeusia  1  6/33 (18.18%)  30 4/77 (5.19%)  12 8/71 (11.27%)  27
Headache  1  2/33 (6.06%)  5 7/77 (9.09%)  37 6/71 (8.45%)  10
Neuropathy peripheral  1  2/33 (6.06%)  9 0/77 (0.00%)  0 6/71 (8.45%)  19
Peripheral sensory neuropathy  1  3/33 (9.09%)  21 0/77 (0.00%)  0 7/71 (9.86%)  55
Syncope  1  0/33 (0.00%)  0 0/77 (0.00%)  0 5/71 (7.04%)  6
Psychiatric disorders       
Anxiety  1  2/33 (6.06%)  6 0/77 (0.00%)  0 5/71 (7.04%)  17
Confusional state  1  3/33 (9.09%)  3 0/77 (0.00%)  0 0/71 (0.00%)  0
Depression  1  0/33 (0.00%)  0 4/77 (5.19%)  29 6/71 (8.45%)  24
Insomnia  1  3/33 (9.09%)  28 10/77 (12.99%)  78 11/71 (15.49%)  80
Respiratory, thoracic and mediastinal disorders       
Cough  1  3/33 (9.09%)  7 4/77 (5.19%)  22 9/71 (12.68%)  39
Dyspnoea  1  5/33 (15.15%)  14 10/77 (12.99%)  90 13/71 (18.31%)  80
Epistaxis  1  3/33 (9.09%)  7 6/77 (7.79%)  43 6/71 (8.45%)  21
Haemoptysis  1  3/33 (9.09%)  8 0/77 (0.00%)  0 0/71 (0.00%)  0
Hiccups  1  0/33 (0.00%)  0 0/77 (0.00%)  0 6/71 (8.45%)  8
Oropharyngeal pain  1  2/33 (6.06%)  10 5/77 (6.49%)  16 5/71 (7.04%)  14
Productive cough  1  2/33 (6.06%)  3 0/77 (0.00%)  0 0/71 (0.00%)  0
Skin and subcutaneous tissue disorders       
Alopecia  1  0/33 (0.00%)  0 4/77 (5.19%)  17 7/71 (9.86%)  44
Dermatitis acneiform  1  17/33 (51.52%)  101 26/77 (33.77%)  254 19/71 (26.76%)  134
Dry skin  1  3/33 (9.09%)  17 19/77 (24.68%)  142 12/71 (16.90%)  87
Erythema  1  0/33 (0.00%)  0 4/77 (5.19%)  9 0/71 (0.00%)  0
Palmar-plantar erythrodysaesthesia syndrome  1  3/33 (9.09%)  11 8/77 (10.39%)  60 6/71 (8.45%)  27
Pruritus  1  5/33 (15.15%)  17 4/77 (5.19%)  34 5/71 (7.04%)  22
Rash  1  7/33 (21.21%)  41 11/77 (14.29%)  91 19/71 (26.76%)  152
Rash maculo-papular  1  0/33 (0.00%)  0 4/77 (5.19%)  13 5/71 (7.04%)  31
Skin fissures  1  3/33 (9.09%)  8 6/77 (7.79%)  48 8/71 (11.27%)  48
Skin ulcer  1  2/33 (6.06%)  6 4/77 (5.19%)  9 5/71 (7.04%)  14
Vascular disorders       
Embolism  1  0/33 (0.00%)  0 4/77 (5.19%)  37 0/71 (0.00%)  0
Hypertension  1  2/33 (6.06%)  26 0/77 (0.00%)  0 0/71 (0.00%)  0
Hypotension  1  2/33 (6.06%)  9 10/77 (12.99%)  27 4/71 (5.63%)  5
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.1
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: Chief Medical Officer
Organization: Eli Lilly and Company
Phone: 800-545-5979
Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01081041     History of Changes
Other Study ID Numbers: 13611
I4E-MC-JXBD ( Other Identifier: Eli Lilly and Company )
First Submitted: March 3, 2010
First Posted: March 5, 2010
Results First Submitted: June 12, 2014
Results First Posted: July 14, 2014
Last Update Posted: April 12, 2017