Study of Erbitux™ (Cetuximab) in Pediatric Patients With Refractory Solid Tumors
- Registration Number
- NCT00110357
- Lead Sponsor
- Eli Lilly and Company
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 48
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Group A Cetuximab + Irinotecan 1-12 years old Group B Cetuximab + Irinotecan 13-18 years old
- Primary Outcome Measures
Name Time Method 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. 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)
- Secondary Outcome Measures
Name Time Method 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 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) up to 168 hours after the start of the cetuximab infusion during the first 21-day cycle of the study 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 Every other 21-day cycle 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 Blood was drawn immediately prior to cetuximab infusions, on a 21-day cycle 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 Participants With a Dose-Limiting Toxicity Prior to each 21-day cycle until dose-limiting toxicities 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).
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 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) up to 168 hours after the start of the cetuximab infusion during the first 21-day cycle of the study 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.
Maximum Plasma Concentration (Cmax) up to 168 hours after the start of the cetuximab infusion during the first 21-day cycle of the study 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.
Number of Deaths, Serious Adverse Events (SAEs), and Adverse Events (AEs) Weekly throughout the study and every 4 weeks thereafter 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 pretreatment visit, prior to each treatment cycle, weekly, and at the end of treatment 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 pretreatment visit, prior to each treatment cycle, weekly, and at the end of treatment 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 pretreatment visit, prior to each treatment cycle, weekly, and at the end of treatment 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 pretreatment visit, prior to each treatment cycle, weekly, and at the end of treatment 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
Trial Locations
- Locations (9)
Sidney Kimmel Cancer Center At Johns Hopkins
🇺🇸Baltimore, Maryland, United States
University Of Florida
🇺🇸Gainesville, Florida, United States
Children'S Healthcare Of Atlanta
🇺🇸Atlanta, Georgia, United States
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
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