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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
DIAGNOSTIC
Masking
NONE
Enrollment
48
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.
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.
Phoenix Children'S Hospital
Phoenix, Arizona, United States
University Of Arizona Health Sciences Center
Tucson, Arizona, United States
The Children'S Hospital
Denver, Colorado, United States
Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RPIID) of Cetuximab in Combination With Irinotecan
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.
Number of Participants With a Dose-Limiting Toxicity
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
Maximum Plasma Concentration (Cmax)
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
Area Under the Curve, Extrapolated to Infinity (AUC[INF])
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
Terminal Half-Life (T-Half)
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.
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University Of Florida
Gainesville, Florida, United States
Children'S Healthcare Of Atlanta
Atlanta, Georgia, United States
Sidney Kimmel Cancer Center At Johns Hopkins
Baltimore, Maryland, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
Vanderbilt University Medical Center Infectious Diseases
Nashville, Tennessee, United States
University Of Texas Md Anderson Cancer Ctr
Houston, Texas, United States
Time frame: up to 168 hours after the start of the cetuximab infusion during the first 21-day cycle of the study
Clearance Corrected for Body Surface Area (CL/BSA)
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
Volume of Distribution at Steady State Corrected for Body Surface Area (VSS/BSA)
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
Tumor Response
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
Human Anti-cetuximab Antibody (HACA) Response
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
Number of Deaths, Serious Adverse Events (SAEs), and Adverse Events (AEs)
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
Grade 3-4 Laboratory Abnormalities - Leukopenia
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
Grade 3-4 Laboratory Abnormalities - Neutropenia
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
Grade 3-4 Laboratory Abnormalities - Thrombocytopenia
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
Grade 3/4 Laboratory Abnormalities - Hypomagnesemia
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