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

Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00110357
• Other study ID #: CA225-085
• Status: Completed
• Phase: Phase 1
• First received: May 6, 2005
• Last updated: November 24, 2015
• Start date: August 2005
• Est. completion date: March 2008

Study information

• Verified date: November 2015
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: March 2008
• Est. primary completion date: March 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 1 Year to 18 Years

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Cancer
• Refractory Solid Tumor

Intervention

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.
• 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.

Locations

Country	Name	City	State
United States	Children'S Healthcare Of Atlanta	Atlanta	Georgia
United States	Sidney Kimmel Cancer Center At Johns Hopkins	Baltimore	Maryland
United States	The Children'S Hospital	Denver	Colorado
United States	University Of Florida	Gainesville	Florida
United States	University Of Texas Md Anderson Cancer Ctr	Houston	Texas
United States	Vanderbilt University Medical Center Infectious Diseases	Nashville	Tennessee
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Phoenix Children'S Hospital	Phoenix	Arizona
United States	University Of Arizona Health Sciences Center	Tucson	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
Eli Lilly and Company	ImClone LLC

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	No
Secondary	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	Yes
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes

External Links

•   BMS Clinical Trials Disclosure
•   For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm