Study of Erbitux™ (Cetuximab) in Pediatric Patients With Refractory Solid Tumors - Full Text View

Sponsor:	Bristol-Myers Squibb
Collaborator:	ImClone LLC
Information provided by (Responsible Party):	Bristol-Myers Squibb
ClinicalTrials.gov Identifier:	NCT00110357

Purpose

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.

Condition	Intervention	Phase
Cancer Refractory Solid Tumor	Drug: Cetuximab + Irinotecan Drug: Cetuximab + Irinotecan	Phase I

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Pharmacokinetics Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Diagnostic
Official Title:	Phase I Study of Erbitux™ (Cetuximab) in Pediatric Patients With Refractory Solid Tumors

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: Irinotecan U 101440E Irinotecan hydrochloride Cetuximab

U.S. FDA Resources

Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:

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)

Secondary Outcome Measures:

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

Enrollment:	48
Study Start Date:	August 2005
Study Completion Date:	March 2008
Primary Completion Date:	March 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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.
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 20 mg/m2 or per dose escalation, administered x5 days x2 weeks, separated by 2 days off, every 21 days.

Eligibility

Ages Eligible for Study:	1 Year to 18 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00110357

Locations

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

Sponsors and Collaborators

Bristol-Myers Squibb

ImClone LLC

Investigators

Study Director:

Bristol-Myers Squibb

More Information

Additional Information:

BMS Clinical Trials Disclosure This link exits the ClinicalTrials.gov site

For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm This link exits the ClinicalTrials.gov site

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. Epub 2009 Sep 21.

Responsible Party:	Bristol-Myers Squibb
ClinicalTrials.gov Identifier:	NCT00110357 History of Changes
Other Study ID Numbers:	CA225-085
Study First Received:	May 6, 2005
Results First Received:	April 21, 2009
Last Updated:	August 23, 2011
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Neoplasms
Irinotecan
Cetuximab
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

Radiation-Sensitizing Agents
Physiological Effects of Drugs
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on February 12, 2012