Study of Erbitux™ (Cetuximab) in Pediatric Patients With Refractory Solid Tumors - Study Results

Study Type:	Interventional
Study Design:	Non-Randomized, Open Label, Uncontrolled, Single Group Assignment
Conditions:	Cancer Refractory Solid Tumor
Interventions:	Drug: Cetuximab + Irinotecan Drug: Cetuximab + Irinotecan

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
48 subjects were enrolled; 1 additional subject withdrew informed consent before any measurements or treatment. 46 subjects (27 in the 1- to 12-yrs-old group and 19 subjects in the 13- to 18-yrs-old group) were treated; 2 subjects in the 13-18 yrs group were not treated, and are NOT included in Participant Flow or Baseline Characteristics tables.

	Description
1- to 12-years-old	No text entered.
13- to 18-years-old	No text entered.

	1- to 12-years-old	13- to 18-years-old
STARTED	27	19
COMPLETED	0^[1]	0^[2]
NOT COMPLETED	27	19
Deterioration without progression	2	0
Disease progression/relapse	20	15
Study Closure	1	0
Study Drug Toxicity	1	3
Withdrawal by Subject	3	1

[1]	Number Still on Study
[2]	Number Still on Study

	Description
1- to 12-years-old	No text entered.
13- to 18-years-old	No text entered.

	1- to 12-years-old	13- to 18-years-old	Total
Number of Participants [units: participants]	27	19	46
Age [units: years] Median ( Full Range )	8.0 ( 1.0 to 12.0 )	16.0 ( 13.0 to 18.0 )	10 ( 1.0 to 18.0 )
Gender [units: participants]
Female	15	9	24
Male	12	10	22
Race/Ethnicity, Customized [units: Participants]
Asian	0	2	2
Black or African American	5	2	7
White	21	14	35
Other	1	1	2
Disease diagnosis [units: Participants]
CNS Primary Tumor	17	9	26
Non-CNS Primary Tumor	10	10	20
Performance Status^[1] [units: Participants]
>70-100	19	16	35
≥50-70	8	3	11
<50	0	0	0

[1]	For participants ≤10 years of age, Lansky play scale is used; for participants >10 years of age, Karnofsky scale is used. The Lansky scale runs from 100 to 0, where 100 is "fully active/normal" and 0 is "unresponsive." Karnofsky score runs from 100 to 0, where 100 is "perfect" health and 0 is death.

Outcome Measures

1. Primary:

Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RPIID) of Cetuximab in Combination With Irinotecan [ Continuous assessment of safety throughout the entire study period and determination of doe-limiting toxicities during and at the end of Cycle 1. ]

Measure Type	Primary
Measure Title	Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RPIID) of Cetuximab in Combination With Irinotecan
Measure Description	MTD of cetuximab intravenous (IV) weekly + irinotecan IV x5 days x2 weeks (in a 3-week cycle) and RPIID of cetuximab IV weekly, as measured by dose-limiting toxicities (see outcome measure 2)
Time Frame	Continuous assessment of safety throughout the entire study period and determination of doe-limiting toxicities during and at the end of Cycle 1.
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
As-treated population

Reporting Groups

	Description
Group A (Ages 1-12 Years)	No text entered.
Group B (Ages 13-18 Years)	No text entered.

Measured Values

	Group A (Ages 1-12 Years)	Group B (Ages 13-18 Years)
Number of Participants Analyzed [units: participants]	27	19
Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RPIID) of Cetuximab in Combination With Irinotecan [units: mg/m2]
MTD cetuximab (in combination w/ irinotecan)	250	250
MTD irinotecan (in combination w/ cetuximab)	16	20
RPIID cetuximab (in combination with irinotecan)	250	250
RPIID irinotecan (in combination with cetuximab)	16	20

No statistical analysis provided for Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RPIID) of Cetuximab in Combination With Irinotecan

2. Secondary:

Number of Participants With a Dose-Limiting Toxicity [ Prior to each 21-day cycle until dose-limiting toxicities ]

Measure Type	Secondary
Measure Title	Number of Participants With a Dose-Limiting Toxicity
Measure Description	Dose-limiting toxicities (DLTs)=serious drug side effects preventing further dose escalation. If 1 of the first 3 subjects developed a DLT during cycle 1 up to 3 additional subjects were enrolled at that dose level. The maximum dose level at which DLTs occurred in fewer than 2 out of 3 to 6 subjects was defined as the Maximum Tolerated Dose (MTD).
Time Frame	Prior to each 21-day cycle until dose-limiting toxicities
Safety Issue	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All treated subjects

Reporting Groups

	Description
Group A: 75/20	Cetuximab 75 mg/m2 + Irinotecan 20 mg/m2 in participants 1-12 years
Group A: 150/20	Cetuximab 150 mg/m2 + Irinotecan 20 mg/m2 in participants 1-12 years of age
Group A 150/16	Cetuximab 150 mg/m2 + Irinotecan 16 mg/m2 in participants 1-12 years of age
Group A: 250/16	Cetuximab 250 mg/m2 + Irinotecan 16 mg/m2 in participants 1-12 years of age
Group B: 75/20	Cetuximab 75 mg/m2 + Irinotecan 20 mg/m2 in participants 13-18 years of age
Group B: 150/20	Cetuximab 150 mg/m2 + Irinotecan 20 mg/m2 in subjects 13-18 years of age
Group B: 250/20	Cetuximab 250 mg/m2 + Irinotecan 20 mg/m2 in participants 13-18 years of age

Measured Values

	Group A: 75/20	Group A: 150/20	Group A 150/16	Group A: 250/16	Group B: 75/20	Group B: 150/20	Group B: 250/20
Number of Participants Analyzed [units: participants]	6	6	3	12	8	4	7
Number of Participants With a Dose-Limiting Toxicity [units: Participants]
Subjects with a dose-limiting toxicity	1	2	0	0	1	0	1
Subjects with no dose-limiting toxicity	5	4	3	12	7	4	6

No statistical analysis provided for Number of Participants With a Dose-Limiting Toxicity

3. Secondary:

Maximum Plasma Concentration (Cmax) [ up to 168 hours after the start of the cetuximab infusion during the first 21-day cycle of the study ]

Measure Type	Secondary
Measure Title	Maximum Plasma Concentration (Cmax)
Measure Description	The single dose pharmacokinetics (PK) of cetuximab was administered with an intravenous dose of irinotecan 16 to 20 mg/m2; Cmax was evaluated based on concentration-time profile.
Time Frame	up to 168 hours after the start of the cetuximab infusion during the first 21-day cycle of the study
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups

	Description
Group A: 75	Cetuximab 75 mg/m2 + Irinotecan 16-20 mg/m2 in participants 1-12 years
Group A :150	Cetuximab 150 mg/m2 + 16-20 mg/m2 in participants 1-12 years of age
Group A: 250	Cetuximab 250 mg/m2 + Irinotecan 16-20 mg/m2 in participants 1-12 years of age
Group B: 75	Cetuximab 75 mg/m2 + Irinotecan 16-20 mg/m2 in participants 13-18 years of age
Group B: 150	Cetuximab 150 mg/m2 + Irinotecan 16-20 mg/m2 in participants 13-18 years of age
Group B: 250	Cetuximab 250 mg/m2 + Irinotecan 16-20 mg/m2 in participants 13-18 years of age

Measured Values

	Group A: 75	Group A :150	Group A: 250	Group B: 75	Group B: 150	Group B: 250
Number of Participants Analyzed [units: participants]	7	7	9	4	2	6
Maximum Plasma Concentration (Cmax) [units: µg/mL] Geometric Mean ± Standard Deviation	50.5 ± 16.7	112.9 ± 24.7	163.7 ± 31.1	53.4 ± 21.7	83.1 ± 13.2	148.5 ± 28.1

No statistical analysis provided for Maximum Plasma Concentration (Cmax)

4. Secondary:

Area Under the Curve, Extrapolated to Infinity (AUC[INF]) [ up to 168 hours after the start of the cetuximab infusion during the first 21-day cycle of the study ]

Measure Type	Secondary
Measure Title	Area Under the Curve, Extrapolated to Infinity (AUC[INF])
Measure Description	The single dose PK of cetuximab was administered with an intravenous dose of irinotecan 16 to 20 mg/m2; AUC(INF) was evaluated based on concentration-time profile.
Time Frame	up to 168 hours after the start of the cetuximab infusion during the first 21-day cycle of the study
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups

	Description
Group A: 75	Cetuximab 75 mg/m2 + Irinotecan 16-20 mg/m2 in participants 1-12 years
Group A :150	Cetuximab 150 mg/m2 + 16-20 mg/m2 in participants 1-12 years of age
Group A: 250	Cetuximab 250 mg/m2 + Irinotecan 16-20 mg/m2 in participants 1-12 years of age
Group B: 75	Cetuximab 75 mg/m2 + Irinotecan 16-20 mg/m2 in participants 13-18 years of age
Group B: 150	Cetuximab 150 mg/m2 + Irinotecan 16-20 mg/m2 in participants 13-18 years of age
Group B: 250	Cetuximab 250 mg/m2 + Irinotecan 16-20 mg/m2 in participants 13-18 years of age

Measured Values

	Group A: 75	Group A :150	Group A: 250	Group B: 75	Group B: 150	Group B: 250
Number of Participants Analyzed [units: participants]	7	7	9	4	2	6
Area Under the Curve, Extrapolated to Infinity (AUC[INF]) [units: µg•h/mL] Geometric Mean ± Standard Deviation	1598.3 ± 863.32	8871.2 ± 1861.1	17706.0 ± 6384.5	1925.2 ± 460.6	7027.3 ± 239.5	13410.4 ± 5484.5

No statistical analysis provided for Area Under the Curve, Extrapolated to Infinity (AUC[INF])

5. Secondary:

Terminal Half-Life (T-Half) [ up to 168 hours after the start of the cetuximab infusion during the first 21-day cycle of the study ]

Measure Type	Secondary
Measure Title	Terminal Half-Life (T-Half)
Measure Description	The single dose PK of cetuximab was administered with an intravenous dose of irinotecan 16 to 20 mg/m2; T-half was evaluated based on concentration-time profile.
Time Frame	up to 168 hours after the start of the cetuximab infusion during the first 21-day cycle of the study
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups

	Description
Group A: 75	Cetuximab 75 mg/m2 + Irinotecan 16-20 mg/m2 in participants 1-12 years
Group A :150	Cetuximab 150 mg/m2 + 16-20 mg/m2 in participants 1-12 years of age
Group A: 250	Cetuximab 250 mg/m2 + Irinotecan 16-20 mg/m2 in participants 1-12 years of age
Group B: 75	Cetuximab 75 mg/m2 + Irinotecan 16-20 mg/m2 in participants 13-18 years of age
Group B: 150	Cetuximab 150 mg/m2 + Irinotecan 16-20 mg/m2 in participants 13-18 years of age
Group B: 250	Cetuximab 250 mg/m2 + Irinotecan 16-20 mg/m2 in participants 13-18 years of age

Measured Values

	Group A: 75	Group A :150	Group A: 250	Group B: 75	Group B: 150	Group B: 250
Number of Participants Analyzed [units: participants]	7	7	9	4	2	6
Terminal Half-Life (T-Half) [units: hours] Mean ± Standard Deviation	31.0 ± 13.9	75.2 ± 18.7	110.3 ± 43.1	37.9 ± 6.3	61.1 ± 10.5	81.9 ± 20.4

No statistical analysis provided for Terminal Half-Life (T-Half)

6. Secondary:

Clearance Corrected for Body Surface Area (CL/BSA) [ up to 168 hours after the start of the cetuximab infusion during the first 21-day cycle of the study ]

Measure Type	Secondary
Measure Title	Clearance Corrected for Body Surface Area (CL/BSA)
Measure Description	The single dose PK of cetuximab was administered with an intravenous dose of irinotecan 16 to 20 mg/m2; CL/BSA was evaluated based on concentration-time profile.
Time Frame	up to 168 hours after the start of the cetuximab infusion during the first 21-day cycle of the study
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups

	Description
Group A: 75	Cetuximab 75 mg/m2 + Irinotecan 16-20 mg/m2 in participants 1-12 years
Group A :150	Cetuximab 150 mg/m2 + 16-20 mg/m2 in participants 1-12 years of age
Group A: 250	Cetuximab 250 mg/m2 + Irinotecan 16-20 mg/m2 in participants 1-12 years of age
Group B: 75	Cetuximab 75 mg/m2 + Irinotecan 16-20 mg/m2 in participants 13-18 years of age
Group B: 150	Cetuximab 150 mg/m2 + Irinotecan 16-20 mg/m2 in participants 13-18 years of age
Group B: 250	Cetuximab 250 mg/m2 + Irinotecan 16-20 mg/m2 in participants 13-18 years of age

Measured Values

	Group A: 75	Group A :150	Group A: 250	Group B: 75	Group B: 150	Group B: 250
Number of Participants Analyzed [units: participants]	7	7	9	4	2	6
Clearance Corrected for Body Surface Area (CL/BSA) [units: L/h/m2] Mean ± Standard Deviation	0.057 ± 0.041	0.017 ± 0.004	0.015 ± 0.005	0.040 ± 0.010	0.021 ± 0.001	0.020 ± 0.009

No statistical analysis provided for Clearance Corrected for Body Surface Area (CL/BSA)

7. Secondary:

Volume of Distribution at Steady State Corrected for Body Surface Area (VSS/BSA) [ up to 168 hours after the start of the cetuximab infusion during the first 21-day cycle of the study ]

Measure Type	Secondary
Measure Title	Volume of Distribution at Steady State Corrected for Body Surface Area (VSS/BSA)
Measure Description	The single dose PK of cetuximab was administered with an intravenous dose of irinotecan 16 to 20 mg/m2; VSS/BSA was evaluated based on concentration-time profile.
Time Frame	up to 168 hours after the start of the cetuximab infusion during the first 21-day cycle of the study
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups

	Description
Group A: 75	Cetuximab 75 mg/m2 + Irinotecan 16-20 mg/m2 in participants 1-12 years
Group A: 150	Cetuximab 150 mg/m2 + 16-20 mg/m2 in participants 1-12 years of age
Group A: 250	Cetuximab 250 mg/m2 + Irinotecan 16-20 mg/m2 in participants 1-12 years of age
Group B: 75	Cetuximab 75 mg/m2 + Irinotecan 16-20 mg/m2 in participants 13-18 years of age
Group B: 150	Cetuximab 150 mg/m2 + Irinotecan 16-20 mg/m2 in participants 13-18 years of age
Group B: 250	Cetuximab 250 mg/m2 + Irinotecan 16-20 mg/m2 in participants 13-18 years of age

Measured Values

	Group A: 75	Group A: 150	Group A: 250	Group B: 75	Group B: 150	Group B: 250
Number of Participants Analyzed [units: participants]	7	7	9	4	2	6
Volume of Distribution at Steady State Corrected for Body Surface Area (VSS/BSA) [units: L/m2] Mean ± Standard Deviation	2.081 ± 0.666	1.860 ± 0.564	2.157 ± 0.362	2.138 ± 0.453	1.887 ± 0.262	2.179 ± 0.250

No statistical analysis provided for Volume of Distribution at Steady State Corrected for Body Surface Area (VSS/BSA)

8. Secondary:

Tumor Response [ Every other 21-day cycle ]

Measure Type	Secondary
Measure Title	Tumor Response
Measure Description	Non-central nervous system (CNS) tumors evaluated using Response Evaluation Criteria In Solid Tumors (RECIST), criteria to define when cancer patients improve ("respond"), stay the same ("stable"), or worsen ("progression"). CNS tumors evaluated based on measurements by investigator, dependence on corticosteroids, and neurologic exam.
Time Frame	Every other 21-day cycle
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All treated subjects

Reporting Groups

	Description
CNS Primary Tumor	No text entered.
Non-CNS Primary Tumor	No text entered.

Measured Values

	CNS Primary Tumor	Non-CNS Primary Tumor
Number of Participants Analyzed [units: participants]	26	20
Tumor Response [units: Participants]
Partial Response	2	0
Stable Disease	10	8
Progressive Disease	10	11
Not Assessable/Unable to Determine	4	1

No statistical analysis provided for Tumor Response

9. Secondary:

Human Anti-cetuximab Antibody (HACA) Response [ Blood was drawn immediately prior to cetuximab infusions, on a 21-day cycle ]

Measure Type	Secondary
Measure Title	Human Anti-cetuximab Antibody (HACA) Response
Measure Description	In order to be considered positive for anti-cetuximab a sample had to: 1) be evaluable (i.e., have a pre and at least one post-treatment timepoint), 2) have an anti-cetuximab value > 7 ng/mL and 3) have a post-treatment sample at least twice the pre-treatment level.
Time Frame	Blood was drawn immediately prior to cetuximab infusions, on a 21-day cycle
Safety Issue	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Cohort comprises all enrolled participants who were tested for HACA. Evaluable participants had normal baseline HACA (≤ 7 ng/dL) and ≥1 postbaseline HACA levels; unevaluable participants either did not have enough sample for analysis or did not have a pre- and postinfusion sample for immunogenicity.

Reporting Groups

	Description
Number of Participants	No text entered.

Measured Values

	Number of Participants
Number of Participants Analyzed [units: participants]	42
Human Anti-cetuximab Antibody (HACA) Response [units: Participants]
Evaluable Participants	27
Unevaluable Participants	15
Participants with positive HACA level	1

No statistical analysis provided for Human Anti-cetuximab Antibody (HACA) Response

10. Secondary:

Number of Deaths, Serious Adverse Events (SAEs), and Adverse Events (AEs) [ Weekly throughout the study and every 4 weeks thereafter ]

Measure Type	Secondary
Measure Title	Number of Deaths, Serious Adverse Events (SAEs), and Adverse Events (AEs)
Measure Description	Toxicity assessments performed at least weekly from the 1st dose of study drug until at least 30 days after the final dose of study drug and thereafter every 4 weeks until all study-related toxicities resolved, returned to baseline, or were deemed irreversible, whichever was longer. Grade 3=severe AE; grade 4=disabling or life threatening.
Time Frame	Weekly throughout the study and every 4 weeks thereafter
Safety Issue	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All treated patients

Reporting Groups

	Description
Group A: 75/20	Cetuximab 75 mg/m2 + Irinotecan 20 mg/m2 in participants 1-12 years
Group A: 150/20	Cetuximab 150 mg/m2 + Irinotecan 20 mg/m2 in participants 1-12 years of age
Group A 150/16	Cetuximab 150 mg/m2 + Irinotecan 16 mg/m2 in participants 1-12 years of age
Group A: 250/16	Cetuximab 250 mg/m2 + Irinotecan 16 mg/m2 in participants 1-12 years of age
Group B: 75/20	Cetuximab 75 mg/m2 + Irinotecan 20 mg/m2 in participants 13-18 years of age
Group B: 150/20	Cetuximab 150 mg/m2 + Irinotecan 20 mg/m2 in subjects 13-18 years of age
Group B: 250/20	Cetuximab 250 mg/m2 + Irinotecan 20 mg/m2 in participants 13-18 years of age

Measured Values

	Group A: 75/20	Group A: 150/20	Group A 150/16	Group A: 250/16	Group B: 75/20	Group B: 150/20	Group B: 250/20
Number of Participants Analyzed [units: participants]	6	6	3	12	8	4	7
Number of Deaths, Serious Adverse Events (SAEs), and Adverse Events (AEs) [units: Participants]
Deaths (total)	0	5	2	5	3	1	1
Deaths within 30 days of last dose	0	2	0	3	0	0	1
SAEs	2	4	0	6	5	3	4
AEs leading to discontinuation of study treatment	0	1	0	0	2	1	0
Grade 3-4 AEs	4	4	2	5	7	4	4

No statistical analysis provided for Number of Deaths, Serious Adverse Events (SAEs), and Adverse Events (AEs)

11. Secondary:

Grade 3-4 Laboratory Abnormalities - Leukopenia [ pretreatment visit, prior to each treatment cycle, weekly, and at the end of treatment ]

Measure Type	Secondary
Measure Title	Grade 3-4 Laboratory Abnormalities - Leukopenia
Measure Description	Blood samples were collected at selected times (pretreatment visit, prior to each treatment cycle, weekly, and at the end of treatment) for clinical laboratory evaluations. Grade 3= Severe AE; Grade 4=Life-threatening or disabling AE
Time Frame	pretreatment visit, prior to each treatment cycle, weekly, and at the end of treatment
Safety Issue	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups

	Description
Group A 75/20	Cetuximab 75 mg/m2 + Irinotecan 20 mg/m2 in participants 1-12 years
Group A 150/16	Cetuximab 150 mg/m2 + Irinotecan 20 mg/m2 in participants 1-12 years of age
Group A 150/20	Cetuximab 150 mg/m2 + Irinotecan 16 mg/m2 in participants 1-12 years of age
Group A 250/16	Cetuximab 250 mg/m2 + Irinotecan 16 mg/m2 in participants 1-12 years of age
Group B 75/20	Cetuximab 75 mg/m2 + Irinotecan 20 mg/m2 in participants 13-18 years of age
Group B 150/20	Cetuximab 150 mg/m2 + Irinotecan 20 mg/m2 in subjects 13-18 years of age
Group B 250/20	Cetuximab 250 mg/m2 + Irinotecan 20 mg/m2 in participants 13-18 years of age

Measured Values

	Group A 75/20	Group A 150/16	Group A 150/20	Group A 250/16	Group B 75/20	Group B 150/20	Group B 250/20
Number of Participants Analyzed [units: participants]	6	3	6	12	7	4	7
Grade 3-4 Laboratory Abnormalities - Leukopenia [units: Participants]	3	0	3	4	2	2	4

No statistical analysis provided for Grade 3-4 Laboratory Abnormalities - Leukopenia

12. Secondary:

Grade 3-4 Laboratory Abnormalities - Neutropenia [ pretreatment visit, prior to each treatment cycle, weekly, and at the end of treatment ]

Measure Type	Secondary
Measure Title	Grade 3-4 Laboratory Abnormalities - Neutropenia
Measure Description	Blood samples were collected at selected times (pretreatment visit, prior to each treatment cycle, weekly, and at the end of treatment) for clinical laboratory evaluations. Grade 3= Severe and undesirable AE; Grade 4=Life-threatening or disabling AE
Time Frame	pretreatment visit, prior to each treatment cycle, weekly, and at the end of treatment
Safety Issue	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups

	Description
Group A 75/20	Cetuximab 75 mg/m2 + Irinotecan 20 mg/m2 in participants 1-12 years
Group A 150/16	Cetuximab 150 mg/m2 + Irinotecan 20 mg/m2 in participants 1-12 years of age
Group A 150/20	Cetuximab 150 mg/m2 + Irinotecan 16 mg/m2 in participants 1-12 years of age
Group A 250/16	Cetuximab 250 mg/m2 + Irinotecan 16 mg/m2 in participants 1-12 years of age
Group B 75/20	Cetuximab 75 mg/m2 + Irinotecan 20 mg/m2 in participants 13-18 years of age
Group B 150/20	Cetuximab 150 mg/m2 + Irinotecan 20 mg/m2 in subjects 13-18 years of age
Group B 250/20	Cetuximab 250 mg/m2 + Irinotecan 20 mg/m2 in participants 13-18 years of age

Measured Values

	Group A 75/20	Group A 150/16	Group A 150/20	Group A 250/16	Group B 75/20	Group B 150/20	Group B 250/20
Number of Participants Analyzed [units: participants]	6	3	4	10	6	3	6
Grade 3-4 Laboratory Abnormalities - Neutropenia [units: Participants]	3	0	3	3	3	1	4

No statistical analysis provided for Grade 3-4 Laboratory Abnormalities - Neutropenia

13. Secondary:

Grade 3-4 Laboratory Abnormalities - Thrombocytopenia [ pretreatment visit, prior to each treatment cycle, weekly, and at the end of treatment ]

Measure Type	Secondary
Measure Title	Grade 3-4 Laboratory Abnormalities - Thrombocytopenia
Measure Description	Blood samples collected at selected times (pretreatment visit, prior to each treatment cycle, weekly, and at the end of treatment) for clinical laboratory evaluations. Grade 3= Severe AE; Grade 4=Life-threatening or disabling AE
Time Frame	pretreatment visit, prior to each treatment cycle, weekly, and at the end of treatment
Safety Issue	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups

	Description
Group A 75/20	Cetuximab 75 mg/m2 + Irinotecan 20 mg/m2 in participants 1-12 years
Group A 150/16	Cetuximab 150 mg/m2 + Irinotecan 20 mg/m2 in participants 1-12 years of age
Group A 150/20	Cetuximab 150 mg/m2 + Irinotecan 16 mg/m2 in participants 1-12 years of age
Group A 250/16	Cetuximab 250 mg/m2 + Irinotecan 16 mg/m2 in participants 1-12 years of age
Group B 75/20	Cetuximab 75 mg/m2 + Irinotecan 20 mg/m2 in participants 13-18 years of age
Group B 150/20	Cetuximab 150 mg/m2 + Irinotecan 20 mg/m2 in subjects 13-18 years of age
Group B 250/20	Cetuximab 250 mg/m2 + Irinotecan 20 mg/m2 in participants 13-18 years of age

Measured Values

	Group A 75/20	Group A 150/16	Group A 150/20	Group A 250/16	Group B 75/20	Group B 150/20	Group B 250/20
Number of Participants Analyzed [units: participants]	6	3	6	12	7	4	7
Grade 3-4 Laboratory Abnormalities - Thrombocytopenia [units: Participants]	1	0	3	2	0	0	4

No statistical analysis provided for Grade 3-4 Laboratory Abnormalities - Thrombocytopenia

14. Secondary:

Grade 3/4 Laboratory Abnormalities - Hypomagnesemia [ pretreatment visit, prior to each treatment cycle, weekly, and at the end of treatment ]

Measure Type	Secondary
Measure Title	Grade 3/4 Laboratory Abnormalities - Hypomagnesemia
Measure Description	Blood samples were collected at selected times (pretreatment visit, prior to each treatment cycle, weekly, and at the end of treatment) for clinical laboratory evaluations. Grade 3= Severe AE; Grade 4=Life-threatening or disabling AE
Time Frame	pretreatment visit, prior to each treatment cycle, weekly, and at the end of treatment
Safety Issue	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups

	Description
Group A 75/20	Cetuximab 75 mg/m2 + Irinotecan 20 mg/m2 in participants 1-12 years
Group A 150/16	Cetuximab 150 mg/m2 + Irinotecan 20 mg/m2 in participants 1-12 years of age
Group A 150/20	Cetuximab 150 mg/m2 + Irinotecan 16 mg/m2 in participants 1-12 years of age
Group A 250/16	Cetuximab 250 mg/m2 + Irinotecan 16 mg/m2 in participants 1-12 years of age
Group B 75/20	Cetuximab 75 mg/m2 + Irinotecan 20 mg/m2 in participants 13-18 years of age
Group B 150/20	Cetuximab 150 mg/m2 + Irinotecan 20 mg/m2 in subjects 13-18 years of age
Group B 250/20	Cetuximab 250 mg/m2 + Irinotecan 20 mg/m2 in participants 13-18 years of age

Measured Values

	Group A 75/20	Group A 150/16	Group A 150/20	Group A 250/16	Group B 75/20	Group B 150/20	Group B 250/20
Number of Participants Analyzed [units: participants]	0	0	0	12	0	0	0
Grade 3/4 Laboratory Abnormalities - Hypomagnesemia [units: Participants]	0	0	0	1	0	0	0

No statistical analysis provided for Grade 3/4 Laboratory Abnormalities - Hypomagnesemia

Responsible Party:	Bristol-Myers Squibb ( Study Director )
Study ID Numbers:	CA225-085
Study First Received:	May 6, 2005
Results First Received:	April 21, 2009
Last Updated:	August 10, 2009
ClinicalTrials.gov Identifier:	NCT00110357 History of Changes
Health Authority:	United States: Food and Drug Administration