Head and Neck Cancer
Conditions
Brief summary
This study will begin with a 30 participant lead-in part: these 30 participants will receive cetuximab manufactured by ImClone on a weekly basis in combination with other chemotherapy drugs \[cisplatin or carboplatin plus 5-fluorouracil (5-FU)\] administered every 3 weeks. After 18 weeks, participants who benefit from this treatment may continue to receive cetuximab once-weekly until progression of the disease, an unacceptable side effect occurs, participants withdraw consent, or the study is closed. In the second part of this study, 200 participants will be randomized in 2 arms: * 100 participants will receive commercial cetuximab manufactured by ImClone (Group A) * 100 participants will receive cetuximab manufactured by Boehringer Ingelheim (Group B). All these 200 participants will receive other chemotherapy drugs (cisplatin or carboplatin plus 5-FU) administered every 3 weeks. After 18 weeks, participants who benefit from this treatment may continue to receive cetuximab once-weekly until progression of the disease, an unacceptable side effect occurs, participants withdraw consent, or the study is closed.
Interventions
DRUGCetuximab
Administered intravenously
DRUGCisplatin
Administered intravenously
DRUGCarboplatin
Administered intravenously
DRUG5-Fluorouracil
Administered intravenously
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Head and neck cancer that was confirmed by tissue biopsy or cytology * Disease not suitable for local therapy * Measurable or evaluable disease * Karnofsky performance status (KPS) score of at least 70 * Organs are functioning well (bone marrow reserve, liver and kidney) * Life expectancy of at least 12 weeks * Signed informed consent document
Exclusion criteria
* Receiving another investigational medication within the last 30 days * Prior chemotherapy, except if given as part of a multimodal treatment for locally advanced head and neck cancer that was completed more than 4 months prior to study entry. * Nasopharyngeal carcinoma * Previous treatment with monoclonal antibody therapy or other signal transduction inhibitors or epidermal growth factor receptor (EGFR) targeting therapy except for prior cetuximab treatment given as part of a multimodal treatment for locally advanced head and neck cancer that was completed more than 4 months prior to study entry. * Uncontrolled high blood pressure * Heart disease or had a heart attack within the last year * Currently have an infection that requires for you to take an IV antibiotic * Currently receiving other therapies for your cancer, such as chemotherapy, radiation therapy, immunotherapy, and hormonal therapy * Medical or psychological condition that would not permit the participant to complete the study or sign informed consent * Known drug abuse (with the exception of alcohol abuse) * Known allergic reaction against any of the components of the study treatment * Second primary malignancy that is clinically detectable at the time of consideration for study enrollment * Have had another type of cancer within the last 2 years * You are currently pregnant or breastfeeding * You are considering becoming pregnant or fathering a child
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Had Treatment-Emergent Adverse Events (TEAEs); Data Analysis Cut-Off: September 27, 2013 | Part 2: Baseline to end of combination therapy (up to 18 weeks) | 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. |
| Number of Participants Who Had TEAEs; Data Analysis Cut-Off: January 23, 2013 | Part 2: Baseline to end of combination therapy or date first participant switched to US commercial cetuximab (up to 18 weeks) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Having a Confirmed Best Response of Complete Response (CR) or Partial Response (PR) (Overall Response Rate [ORR]) | Parts 1 and 2: Randomization to Progression of Disease (Up to 32.7 Months) | 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. |
| Number of Participants With Anti-Cetuximab Antibodies | Day 1, Week 1 of Cycles 3 and 5 (postbaseline samples were collected prior to infusion). | — |
| Percentage of Participants Having a Best Response of CR, PR, or Stable Disease (SD) - Disease Control Rate (DCR) | Parts 1 and 2: Randomization to Progression of Disease (Up to 32.7 Months) | 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. |
| Overall Survival (OS) | Parts 1 and 2: Randomization to Date of Death from any Cause (Up to 36.3 Months) | 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. |
| Cmax of Cetuximab at Steady State | 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 | 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. |
| Area Under the Concentration Curve (AUC) of Cetuximab at Steady State | 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 | 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. |
| Maximum Serum Concentration (Cmax) of Cetuximab Following 400 mg/m² Cetuximab Dosing | Part 2: Cycle 1, Day 1: 0 hours [(h); immediately postdose], 1 h, 2 h, and 24 h postdose | 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. |
| Progression-Free Survival (PFS) | Parts 1 and 2: Randomization to Progression of Disease or Death from any Cause (Up to 32.7 Months) | 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. |
Countries
Canada, Mexico, United States
Participant flow
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.
Participants by arm
| Arm | Count |
|---|---|
| Part 1: Safety Lead-In (Cetuximab, Cis or Carbo, 5-FU) 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. | 33 |
| Part 2: Cetuximab (US Commercial), Cis or Carbo, 5-FU 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. | 77 |
| Part 2: Cetuximab (Manufactured by BI), Cis or Carbo, 5-FU 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. | 71 |
| Total | 181 |
Baseline characteristics
| Characteristic | Part 1: Safety Lead-In (Cetuximab, Cis or Carbo, 5-FU) | Total | Part 2: Cetuximab (Manufactured by BI), Cis or Carbo, 5-FU | Part 2: Cetuximab (US Commercial), Cis or Carbo, 5-FU |
|---|---|---|---|---|
| Age, Continuous | 62.9 years STANDARD_DEVIATION 8.74 | 59.0 years STANDARD_DEVIATION 10.47 | 59.4 years STANDARD_DEVIATION 10.49 | 57.1 years STANDARD_DEVIATION 10.75 |
| Disease Stage at Study Entry Locoregional | 6 participants | 72 participants | 32 participants | 34 participants |
| Disease Stage at Study Entry Metastatic | 27 participants | 108 participants | 38 participants | 43 participants |
| Disease Stage at Study Entry Unknown or not reported | 0 participants | 1 participants | 1 participants | 0 participants |
| Karnofsky Performance Status (KPS) KPS 100 | 4 participants | 23 participants | 11 participants | 8 participants |
| Karnofsky Performance Status (KPS) KPS 70 | 5 participants | 21 participants | 7 participants | 9 participants |
| Karnofsky Performance Status (KPS) KPS 80 | 19 participants | 69 participants | 22 participants | 28 participants |
| Karnofsky Performance Status (KPS) KPS 90 | 5 participants | 68 participants | 31 participants | 32 participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 2 participants | 27 participants | 9 participants | 16 participants |
| Race/Ethnicity, Customized Asian | 0 participants | 3 participants | 2 participants | 1 participants |
| Race/Ethnicity, Customized Black or African American | 2 participants | 11 participants | 2 participants | 7 participants |
| Race/Ethnicity, Customized More than 1 race | 0 participants | 1 participants | 1 participants | 0 participants |
| Race/Ethnicity, Customized Unknown or Not Reported | 0 participants | 1 participants | 1 participants | 0 participants |
| Race/Ethnicity, Customized White | 29 participants | 138 participants | 56 participants | 53 participants |
| Region of Enrollment Canada | 5 participants | 61 participants | 27 participants | 29 participants |
| Region of Enrollment Mexico | 1 participants | 39 participants | 15 participants | 23 participants |
| Region of Enrollment United States | 27 participants | 80 participants | 28 participants | 25 participants |
| Sex/Gender, Customized Female | 11 participants | 35 participants | 15 participants | 9 participants |
| Sex/Gender, Customized Male | 22 participants | 145 participants | 55 participants | 68 participants |
| Sex/Gender, Customized Unknown or Not Reported | 0 participants | 1 participants | 1 participants | 0 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 32 / 33 | 64 / 77 | 62 / 71 |
| serious Total, serious adverse events | 20 / 33 | 48 / 77 | 42 / 71 |
Outcome results
Primary
Number of Participants Who Had TEAEs; Data Analysis Cut-Off: January 23, 2013
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)
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| Part 2: Combination Therapy: Cetuximab (US Commercial) | Number of Participants Who Had TEAEs; Data Analysis Cut-Off: January 23, 2013 | 75 participants |
| Part 2: Combination Therapy: Cetuximab (Manufactured by BI) | Number of Participants Who Had TEAEs; Data Analysis Cut-Off: January 23, 2013 | 68 participants |
Primary
Number of Participants Who Had Treatment-Emergent Adverse Events (TEAEs); Data Analysis Cut-Off: September 27, 2013
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)
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| Part 2: Combination Therapy: Cetuximab (US Commercial) | Number of Participants Who Had Treatment-Emergent Adverse Events (TEAEs); Data Analysis Cut-Off: September 27, 2013 | 76 participants |
| Part 2: Combination Therapy: Cetuximab (Manufactured by BI) | Number of Participants Who Had Treatment-Emergent Adverse Events (TEAEs); Data Analysis Cut-Off: September 27, 2013 | 68 participants |
Secondary
Area Under the Concentration Curve (AUC) of Cetuximab at Steady State
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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 2: Combination Therapy: Cetuximab (US Commercial) | Area Under the Concentration Curve (AUC) of Cetuximab at Steady State | 21900 micrograms*hours/milliliter (μg*h/mL) | Geometric Coefficient of Variation 31.8 |
| Part 2: Combination Therapy: Cetuximab (Manufactured by BI) | Area Under the Concentration Curve (AUC) of Cetuximab at Steady State | 18800 micrograms*hours/milliliter (μg*h/mL) | Geometric Coefficient of Variation 25.5 |
Secondary
Cmax of Cetuximab at Steady State
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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 2: Combination Therapy: Cetuximab (US Commercial) | Cmax of Cetuximab at Steady State | 225 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 17.7 |
| Part 2: Combination Therapy: Cetuximab (Manufactured by BI) | Cmax of Cetuximab at Steady State | 199 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 15.3 |
Secondary
Maximum Serum Concentration (Cmax) of Cetuximab Following 400 mg/m² Cetuximab Dosing
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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 2: Combination Therapy: Cetuximab (US Commercial) | Maximum Serum Concentration (Cmax) of Cetuximab Following 400 mg/m² Cetuximab Dosing | 208 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 10.2 |
| Part 2: Combination Therapy: Cetuximab (Manufactured by BI) | Maximum Serum Concentration (Cmax) of Cetuximab Following 400 mg/m² Cetuximab Dosing | 208 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 7.8 |
Secondary
Number of Participants With Anti-Cetuximab Antibodies
Time frame: Day 1, Week 1 of Cycles 3 and 5 (postbaseline samples were collected prior to infusion).
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| Part 2: Combination Therapy: Cetuximab (US Commercial) | Number of Participants With Anti-Cetuximab Antibodies | 4 participants |
Secondary
Overall Survival (OS)
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)
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Part 2: Combination Therapy: Cetuximab (US Commercial) | Overall Survival (OS) | 9.13 Months |
| Part 2: Combination Therapy: Cetuximab (Manufactured by BI) | Overall Survival (OS) | 9.23 Months |
| Part 2: Combination Therapy: Cetuximab (Manufactured by BI) | Overall Survival (OS) | 9.46 Months |
Secondary
Percentage of Participants Having a Best Response of CR, PR, or Stable Disease (SD) - Disease Control Rate (DCR)
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)
Population: All participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 2: Combination Therapy: Cetuximab (US Commercial) | Percentage of Participants Having a Best Response of CR, PR, or Stable Disease (SD) - Disease Control Rate (DCR) | 69.7 percentage of participants |
| Part 2: Combination Therapy: Cetuximab (Manufactured by BI) | Percentage of Participants Having a Best Response of CR, PR, or Stable Disease (SD) - Disease Control Rate (DCR) | 58.4 percentage of participants |
| Part 2: Combination Therapy: Cetuximab (Manufactured by BI) | Percentage of Participants Having a Best Response of CR, PR, or Stable Disease (SD) - Disease Control Rate (DCR) | 62.0 percentage of participants |
Secondary
Percentage of Participants Having a Confirmed Best Response of Complete Response (CR) or Partial Response (PR) (Overall Response Rate [ORR])
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)
Population: All participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 2: Combination Therapy: Cetuximab (US Commercial) | Percentage of Participants Having a Confirmed Best Response of Complete Response (CR) or Partial Response (PR) (Overall Response Rate [ORR]) | 24.2 percentage of participants |
| Part 2: Combination Therapy: Cetuximab (Manufactured by BI) | Percentage of Participants Having a Confirmed Best Response of Complete Response (CR) or Partial Response (PR) (Overall Response Rate [ORR]) | 32.5 percentage of participants |
| Part 2: Combination Therapy: Cetuximab (Manufactured by BI) | Percentage of Participants Having a Confirmed Best Response of Complete Response (CR) or Partial Response (PR) (Overall Response Rate [ORR]) | 36.6 percentage of participants |
Secondary
Progression-Free Survival (PFS)
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)
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Part 2: Combination Therapy: Cetuximab (US Commercial) | Progression-Free Survival (PFS) | 4.57 Months |
| Part 2: Combination Therapy: Cetuximab (Manufactured by BI) | Progression-Free Survival (PFS) | 4.34 Months |
| Part 2: Combination Therapy: Cetuximab (Manufactured by BI) | Progression-Free Survival (PFS) | 5.59 Months |