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.

Study Overview

• Status: Completed
• Conditions: Cancer; Refractory Solid Tumor
• Intervention / Treatment: Drug: Cetuximab + Irinotecan; Drug: Cetuximab + Irinotecan

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Phoenix Children's Hospital
    • Tucson, Arizona, United States, 85724
      • University of Arizona Health Sciences Center
  • Colorado
    • Denver, Colorado, United States, 80218
      • The Children's Hospital
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Children's Healthcare of Atlanta
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Sidney Kimmel Cancer Center at Johns Hopkins
  • New York
    • New York, New York, United States, 10021
      • Memorial Sloan Kettering Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center Infectious Diseases
  • Texas
    • Houston, Texas, United States, 77030
      • University Of Texas Md Anderson Cancer Ctr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 18 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Group A; 1-12 years old	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 B; 13-18 years old	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	Continuous assessment of safety throughout the entire study period and determination of doe-limiting toxicities during and at the end of Cycle 1.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	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.	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.	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.	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.	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.	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.	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.	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.	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	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	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	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	pretreatment visit, prior to each treatment cycle, weekly, and at the end of treatment

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Publications and helpful links

General Publications

• 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. doi: 10.1200/JCO.2008.20.8975. Epub 2009 Sep 21.

Study record dates

Study Major Dates

• Study Start: August 1, 2005
• Primary Completion (ACTUAL): March 1, 2008
• Study Completion (ACTUAL): March 1, 2008

Study Registration Dates

• First Submitted: May 6, 2005
• First Submitted That Met QC Criteria: May 6, 2005
• First Posted (ESTIMATE): May 9, 2005

Study Record Updates

• Last Update Posted (ESTIMATE): December 24, 2015
• Last Update Submitted That Met QC Criteria: November 24, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Topoisomerase I Inhibitors; Irinotecan; Cetuximab
• Other Study ID Numbers: CA225-085