The purpose of this study is to determine if IMC-A12 is safe for participants, and also to determine the best dose of IMC-A12 to give to participants.
The purpose of this study is to establish the safety profile and maximum tolerated dose (MTD) of the anti-IGF-IR monoclonal antibody IMC-A12 administered weekly in participants with advanced solid tumors who no longer respond to standard therapy or for whom no standard therapy is available
Study Type
INTERVENTIONAL
Purpose
TREATMENT
Masking
NONE
Enrollment
24
Cohort 1 3 milligrams/kilogram (mg/kg), I.V. once a week, for 4 weeks, followed by a 2-week observation period.
Cohort 2 6 mg/kg, I.V. once a week, for 4 weeks, followed by a 2-week observation period.
Cohort 3 10 mg/kg, I.V. once a week, for 4 weeks, followed by a 2-week observation period.
ImClone Investigational Site
Scottsdale, Arizona, United States
ImClone Investigational Site
Detroit, Michigan, United States
ImClone Investigational Site
Seattle, Washington, United States
Number of Participants With Adverse Events (AEs) or Deaths
Data presented are the number of participants who experienced serious adverse events (SAEs), other non-serious AEs and deaths during the study including the 30-day follow-up. A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Event module.
Time frame: Enrollment to study completion up to 215 weeks
Maximum Tolerated Dose (MTD)
The MTD was defined as the dose preceding the dose level at which 2 participants experienced a dose-limiting toxicity (DLT). A DLT was defined as any Grade 3 or 4 hematologic or nonhematologic toxicity based on Common Terminology Criteria for AE (CTCAE), excluding alopecia, which was considered by the investigator to be definitely, probably, or possibly related to IMC-A12.
Time frame: 6 weeks
Maximum Concentration (Cmax) of IMC-A12 Following Multiple Doses
Time frame: Predose, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 hours after the infusion of Cycle 1
Observed Serum Concentration of IMC-A12 at 168 Hour Post End of Infusion Following Multiple Doses
Time frame: Predose, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 hours after the infusion of Cycle 1
Area Under the Serum Concentration Versus Time Curve of IMC-A12 During One Dosing Interval (AUCτ) Following Multiple Doses
Time frame: Predose, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 hours after the infusion of Cycle 1
Half-Life (t1/2) of IMC-A12 Following Multiple Doses
Half-Life (t1/2) is the time measured for the plasma concentration of the drug to decrease by one half. The analysis was not performed for the 6 mg/kg and 10 mg/kg dosing groups due to insufficient PK data.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Cohort 4 15 mg/kg, I.V. once a week, for 4 weeks, followed by a 2-week observation period.
Cohort 5 21 mg/kg, I.V. once a week, for 4 weeks, followed by a 2-week observation period.
Cohort 6 27 mg/kg, I.V. once a week, for 4 weeks, followed by a 2-week observation period.
Time frame: Predose, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 hours after the infusion of Cycle 1
Clearance Rate of IMC-A12 at Steady State (CLss) Following Multiple Doses
CLss is the volume of plasma (or blood) from which the drug is completely removed, or cleared, in a given time at steady-state.
Time frame: Predose, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 hours after the infusion of Cycle 1
Volume of Distribution of IMC-A12 at Steady State (Vss) Following Multiple Doses
Vss is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug at steady-state. The analysis was not performed for the 6 mg/kg and 10 mg/kg dosing groups due to insufficient PK data.
Time frame: Predose, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 hours after the infusion of Cycle 1
Serum Anti-IMC-A12 Antibody Assessment (Immunogenicity)
Analysis was not performed due to lack of available assay.
Time frame: Before the last infusion of each treatment cycle
Number of Participants With Best Overall Response
Stable Disease (SD) is neither sufficient shrinkage to qualify for partial response (PR) nor sufficient increase to qualify for progressive disease (PD). PR and PD were assessed by investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.0. PR is ≥30% decrease in sum of longest diameter of target lesions. PD is ≥20% increase in sum of longest diameter of target lesions and/or a new lesion. Participants with a global deterioration of their health status requiring discontinuation of treatment without objective evidence of disease progression at that time were to be reported as "symptomatic deterioration"
Time frame: Enrollment to study completion up to 215 weeks