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

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Pre-Assignment Details

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.

Reporting Groups

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

Participant Flow: Overall Study

	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

Baseline Characteristics

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Reporting Groups

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

Baseline Measures

	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

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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. ]

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2. Secondary:

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

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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 ]

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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 ]

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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 ]

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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 ]

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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 ]

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8. Secondary:

Tumor Response [ Every other 21-day cycle ]

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9. Secondary:

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

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10. Secondary:

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

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11. Secondary:

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

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12. Secondary:

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

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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 ]

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14. Secondary:

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

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Serious Adverse Events

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Other Adverse Events

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More Information

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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.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial’s primary publication.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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Results Point of Contact:

Name/Title: BMS Study Director
Organization: Bristol-Myers Squibb
e-mail: Clinical.Trials@bms.com

No publications provided

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