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

This study has been completed.
Sponsor:
Collaborator:
ImClone LLC
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00110357
First received: May 6, 2005
Last updated: August 23, 2011
Last verified: August 2011

May 6, 2005
August 23, 2011
August 2005
March 2008   (final data collection date for primary outcome measure)
Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RPIID) of Cetuximab in Combination With Irinotecan [ 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. ] [ Designated as safety issue: No ]
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)
Not Provided
Complete list of historical versions of study NCT00110357 on ClinicalTrials.gov Archive Site
  • Number of Participants With a Dose-Limiting Toxicity [ Time Frame: Prior to each 21-day cycle until dose-limiting toxicities ] [ Designated as safety issue: Yes ]
    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).
  • Maximum Plasma Concentration (Cmax) [ Time Frame: up to 168 hours after the start of the cetuximab infusion during the first 21-day cycle of the study ] [ Designated as safety issue: No ]
    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.
  • Area Under the Curve, Extrapolated to Infinity (AUC[INF]) [ Time Frame: up to 168 hours after the start of the cetuximab infusion during the first 21-day cycle of the study ] [ Designated as safety issue: No ]
    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.
  • Terminal Half-Life (T-Half) [ Time Frame: up to 168 hours after the start of the cetuximab infusion during the first 21-day cycle of the study ] [ Designated as safety issue: No ]
    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.
  • Clearance Corrected for Body Surface Area (CL/BSA) [ Time Frame: up to 168 hours after the start of the cetuximab infusion during the first 21-day cycle of the study ] [ Designated as safety issue: No ]
    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.
  • Volume of Distribution at Steady State Corrected for Body Surface Area (VSS/BSA) [ Time Frame: up to 168 hours after the start of the cetuximab infusion during the first 21-day cycle of the study ] [ Designated as safety issue: No ]
    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.
  • Tumor Response [ Time Frame: Every other 21-day cycle ] [ Designated as safety issue: No ]
    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.
  • Human Anti-cetuximab Antibody (HACA) Response [ Time Frame: Blood was drawn immediately prior to cetuximab infusions, on a 21-day cycle ] [ Designated as safety issue: Yes ]
    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.
  • Number of Deaths, Serious Adverse Events (SAEs), and Adverse Events (AEs) [ Time Frame: Weekly throughout the study and every 4 weeks thereafter ] [ Designated as safety issue: Yes ]
    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.
  • Grade 3-4 Laboratory Abnormalities - Leukopenia [ Time Frame: pretreatment visit, prior to each treatment cycle, weekly, and at the end of treatment ] [ Designated as safety issue: Yes ]
    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
  • Grade 3-4 Laboratory Abnormalities - Neutropenia [ Time Frame: pretreatment visit, prior to each treatment cycle, weekly, and at the end of treatment ] [ Designated as safety issue: Yes ]
    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
  • Grade 3-4 Laboratory Abnormalities - Thrombocytopenia [ Time Frame: pretreatment visit, prior to each treatment cycle, weekly, and at the end of treatment ] [ Designated as safety issue: Yes ]
    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
  • Grade 3/4 Laboratory Abnormalities - Hypomagnesemia [ Time Frame: pretreatment visit, prior to each treatment cycle, weekly, and at the end of treatment ] [ Designated as safety issue: Yes ]
    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
Not Provided
Not Provided
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Study of Erbitux™ (Cetuximab) in Pediatric Patients With Refractory Solid Tumors
Phase I Study of Erbitux™ (Cetuximab) in Pediatric Patients With Refractory Solid Tumors

The purpose of this clinical research study is to establish the maximum tolerated dose and recommended Phase II dose of Erbitux™ in combination with Irinotecan in pediatric and adolescent patients with refractory solid tumors.

Not Provided
Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
  • Cancer
  • Refractory Solid Tumor
  • Drug: Cetuximab + Irinotecan
    Intravenous (IV) cetuximab 75 - 250 mg/m2 depending on dose escalation for MTD, weekly; irinotecan was administered at a dose of 16 or 20 mg/m2 or per dose escalation, administered x5 days x2 weeks, separated by 2 days off, every 21 days.
  • Drug: Cetuximab + Irinotecan
    Intravenous (IV) cetuximab 75 - 250 mg/m2 depending on dose escalation for MTD, weekly; irinotecan was administered at a dose of 20 mg/m2 or per dose escalation, administered x5 days x2 weeks, separated by 2 days off, every 21 days.
  • Active Comparator: Group A
    1-12 years old
    Intervention: Drug: Cetuximab + Irinotecan
  • Active Comparator: Group B
    13-18 years old
    Intervention: Drug: Cetuximab + Irinotecan
Trippett TM, Herzog C, Whitlock JA, Wolff J, Kuttesch J, Bagatell R, Hunger SP, Boklan J, Smith AA, Arceci RJ, Katzenstein HM, Harbison C, Zhou X, Lu H, Langer C, Weber M, Gore L. Phase I and pharmacokinetic study of cetuximab and irinotecan in children with refractory solid tumors: a study of the pediatric oncology experimental therapeutic investigators' consortium. J Clin Oncol. 2009 Oct 20;27(30):5102-8. Epub 2009 Sep 21.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
48
March 2008
March 2008   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Histologically or cytologically confirmed diagnosis of a solid tumor which has progressed on, or following standard therapy, or for which no standard effective therapy is known.
  • Children age 1-18 years.

Exclusion Criteria:

  • Presence of active infection.
  • Requirement to receive concurrent chemotherapy immunotherapy, radiotherapy, or any other investigational drug while on study.
  • Inadequate bone marrow, hepatic, or renal function.
Both
1 Year to 18 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00110357
CA225-085
No
Bristol-Myers Squibb
Bristol-Myers Squibb
ImClone LLC
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
Bristol-Myers Squibb
August 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP