Antineoplastic Agents

All Drugs and Chemicals

Irinotecan

Cetuximab

Topoisomerase I Inhibitors

Enzyme Inhibitors

Antineoplastic Agents, Immunological

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.

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

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

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)

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).

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.

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.

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.

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.

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.

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.

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.

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.

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

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

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

Eli Lilly and Company

01 75 mg/m2 CET + 20 mg/m2 IRI

02 150 mg/m2 CET + 20 mg/m2 IRI

03 150 mg/m2 CET + 16 mg/m2 IRI

04 250 mg/m2 CET + 16 mg/m2 IRI

05 250 mg/m2 CET + 20 mg/m2 IRI

1- to 12-years-old

13- to 18-years-old

Total

Age, Continuous

Sex: Female, Male

Asian

Black or African American

White

Other

Race/Ethnicity, Customized

CNS Primary Tumor

Non-CNS Primary Tumor

Disease diagnosis

>70-100

≥50-70

For participants ≤10 years of age, Lansky play scale is used; for participants \>10 years of age, Karnofsky scale is used. The Lansky scale runs from 100 to 0, where 100 is "fully active/normal" and 0 is "unresponsive." Karnofsky score runs from 100 to 0, where 100 is "perfect" health and 0 is death.

Performance Status

Chief Medical Officer

Subjects with a dose-limiting toxicity

Subjects with no dose-limiting toxicity

Cetuximab 75 mg/m2 + Irinotecan 20 mg/m2 in participants 1-12 years

Group A: 75/20

Cetuximab 150 mg/m2 + Irinotecan 20 mg/m2 in participants 1-12 years of age

Group A: 150/20

Cetuximab 150 mg/m2 + Irinotecan 16 mg/m2 in participants 1-12 years of age

Group A 150/16

Cetuximab 250 mg/m2 + Irinotecan 16 mg/m2 in participants 1-12 years of age

Group A: 250/16

Cetuximab 75 mg/m2 + Irinotecan 20 mg/m2 in participants 13-18 years of age

Group B: 75/20

Cetuximab 150 mg/m2 + Irinotecan 20 mg/m2 in subjects 13-18 years of age

Group B: 150/20

Cetuximab 250 mg/m2 + Irinotecan 20 mg/m2 in participants 13-18 years of age

Group B: 250/20

Number of Participants With a Dose-Limiting Toxicity

Cetuximab 75 mg/m2 + Irinotecan 16-20 mg/m2 in participants 1-12 years

Group A: 75

Cetuximab 150 mg/m2 + 16-20 mg/m2 in participants 1-12 years of age

Group A :150

Cetuximab 250 mg/m2 + Irinotecan 16-20 mg/m2 in participants 1-12 years of age

Group A: 250

Cetuximab 75 mg/m2 + Irinotecan 16-20 mg/m2 in participants 13-18 years of age

Group B: 75

Cetuximab 150 mg/m2 + Irinotecan 16-20 mg/m2 in participants 13-18 years of age

Group B: 150

Cetuximab 250 mg/m2 + Irinotecan 16-20 mg/m2 in participants 13-18 years of age

Group B: 250

Maximum Plasma Concentration (Cmax)

Area Under the Curve, Extrapolated to Infinity (AUC[INF])

Terminal Half-Life (T-Half)

Clearance Corrected for Body Surface Area (CL/BSA)

Group A: 150

Volume of Distribution at Steady State Corrected for Body Surface Area (VSS/BSA)

Partial Response

Stable Disease

Progressive Disease

Not Assessable/Unable to Determine

Tumor Response

Evaluable Participants

Unevaluable Participants

Participants with positive HACA level

Number of Participants

Cohort comprises all enrolled participants who were tested for HACA. Evaluable participants had normal baseline HACA (≤ 7 ng/dL) and ≥1 postbaseline HACA levels; unevaluable participants either did not have enough sample for analysis or did not have a pre- and postinfusion sample for immunogenicity.

Spots Global Cancer Trial Database for cetuximab + irinotecan