The purpose of this study is to investigate whether there are no clinically significant pharmacokinetic effects of concomitant ramucirumab (IMC-1121B) on paclitaxel by investigating the pharmacokinetics (PK) of each in participants with advanced malignant solid tumors. Part A of this study will investigate the potential of concomitant ramucirumab (IMC-1121B) to affect the pharmacokinetics of paclitaxel. Part B of this study will investigate the pharmacokinetics of ramucirumab (IMC-1121B) as monotherapy.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
48
ramucirumab (IMC-1121B) 8 milligrams/kilogram (mg/kg) intravenous infusion, administered on Day 1and Day 15 of each 4-week cycle, unless otherwise specified.
paclitaxel 80 milligrams/square meter (mg/m²) intravenous infusion, administered on Days 1, 8 and 15 of each 4-week cycle, unless otherwise specified.
ImClone Investigational Site
Ann Arbor, Michigan, United States
ImClone Investigational Site
Detroit, Michigan, United States
ImClone Investigational Site
New Brunswick, New Jersey, United States
ImClone Investigational Site
Cleveland, Ohio, United States
Part A: Pharmacokinetics - Dose-Normalized Area Under the Concentration Versus Time Curve of Paclitaxel From Time Zero to Infinity [AUC(0-∞)] in Cycle 1
Dose-normalized AUC(0-∞) was calculated from AUC(0-∞) divided by the dose. Data presented are Geometric Least Squares (Geo LS) means. Geo LS means were adjusted for cycle, participant and random error.
Time frame: Cycle 1: 0, 1, 1.5, 2, 5, 7, 24, 48, 72 and 168 hours post paclitaxel infusion
Part A: Pharmacokinetics - Dose-Normalized Area Under the Concentration Versus Time Curve of Paclitaxel From Time Zero to Infinity [AUC(0-∞)] in Cycle 2
Dose-normalized AUC(0-∞) was calculated from AUC(0-∞) divided by the dose. Data presented are Geometric Least Squares (Geo LS) means. Geo LS means were adjusted for cycle, participant and random error.
Time frame: Cycle 2: -1, 0, 1, 1.5, 2, 5, 7, 24, 48, 72, 96, 168, 264 and 336 hours post paclitaxel infusion
Part A: Pharmacokinetics - Dose-Normalized Maximum Observed Drug Concentration (Cmax) of Paclitaxel in Cycle 1
Dose-normalized Cmax was calculated from Cmax divided by the dose. Data presented are Geometric Least Squares (Geo LS) means. Geo LS means were adjusted for cycle, participant and random error.
Time frame: Cycle 1: 0,1, 1.5, 2, 5, 7, 24, 48, 72 and 168 hours post paclitaxel infusion
Part A: Pharmacokinetics - Dose-Normalized Maximum Observed Drug Concentration (Cmax) of Paclitaxel in Cycle 2
Dose-normalized Cmax was calculated from Cmax divided by the dose. Data presented are Geometric Least Squares (Geo LS) means. Geo LS means were adjusted for cycle, participant and random error.
Time frame: Cycle 2: -1, 0, 1, 1.5, 2, 5, 7, 24, 48, 72, 96, 168, 264 and 336 hours post paclitaxel infusion
Part B: Pharmacokinetics - Dose-Normalized Area Under the Concentration Versus Time Curve of Ramucirumab From Time Zero to Infinity [AUC(0-∞)] as Monotherapy
Dose-normalized AUC(0-∞) was calculated from AUC(0-∞) divided by the dose.
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ImClone Investigational Site
Philadelphia, Pennsylvania, United States
ImClone Investigational Site
Seattle, Washington, United States
Time frame: Cycle 1: 0,1, 1.5, 2, 5, 7, 24, 48, 72,168, 264, 336, 408, and 504 hours post ramucirumab infusion
Part A: Pharmacokinetics - Dose-Normalized Area Under the Concentration Versus Time Curve of Ramucirumab From Time Zero to Infinity [AUC(0-∞)] in the Presence of Paclitaxel
Dose-normalized AUC(0-∞) was calculated from AUC(0-∞) divided by the dose.
Time frame: Cycle 2: 0, 1, 2, 2.5, 3, 6, 8, 25, 49, 73, 97, 169, 265 and 337 hours post ramucirumab infusion
Part A: Pharmacokinetics - Dose-Normalized Maximum Observed Drug Concentration (Cmax) of Ramucirumab in the Presence of Paclitaxel
Dose-normalized Cmax was calculated from Cmax divided by the dose.
Time frame: Cycle 2: 0, 1, 2, 2.5, 3, 6, 8, 25, 49, 73, 97, 169, 265 and 337 hours post ramucirumab infusion
Part A: Immunogenicity of Ramucirumab in Combination With Paclitaxel - Number of Participants With Anti-Ramucirumab Antibodies
Number of participants with positive treatment emergent anti-ramucirumab antibodies was summarized by treatment group. A treatment-emergent anti-drug antibodies (TEADA) sample was defined as: a post treatment sample with at least a 4-fold increase in titer from pre treatment sample; or 1:20 post treatment titer for participants that had no detectable ADA titer at baseline.
Time frame: -1 hour on Day 1 of Cycle 2, and 30 days after last dose of study drug
Part B: Immunogenicity of Ramucirumab as Monotherapy - Number of Participants With Anti-Ramucirumab Antibodies
Number of participants with positive treatment emergent anti-ramucirumab antibodies was summarized by treatment group. A treatment-emergent anti-drug antibodies (TEADA) sample was defined as: a post treatment sample with at least a 4-fold increase in titer from pre treatment sample; or 1:20 post treatment titer for participants that had no detectable ADA titer at baseline.
Time frame: 0 hour on Day 1 of Cycle 1, and 30 days after last dose of study drug