The purpose of this study is to determine if Ramucirumab (IMC-1121B) causes prolongation of the QT/QTc interval in participants with advanced cancer.
The primary purpose of this study is to determine if treatment with ramucirumab causes prolongation of the QTc/QT interval in participants with advanced cancer, to assess the safety and tolerability of ramucirumab therapy, and to evaluate the pharmacokinetic (PK) characteristics of ramucirumab
Study Type
INTERVENTIONAL
Allocation
NA
Masking
NONE
Enrollment
68
IMC-1121B (Ramucirumab) 10 mg/kg intravenously (IV) over 60 minutes, once every 3 weeks for minimum of 9 weeks.
Administered orally
Administered IV
ImClone Investigational Site
Atlanta, Georgia, United States
ImClone Investigational Site
Metairie, Louisiana, United States
ImClone Investigational Site
Ann Arbor, Michigan, United States
ImClone Investigational Site
Philadelphia, Pennsylvania, United States
Change From Baseline to Cycle 3 in QT/Corrected QT (QTc) Interval Prolongation in Participants
All electrocardiogram (ECG) tests were performed in triplicate prior to ramucirumab treatment. QT is the interval between the Q and T waves and QTc is the QT corrected for heart rate using Fridericia's formula: QTc = QT/RR\^0.33 where RR is the interval between 2 R waves. Each participant's mean QT/QTc value was calculated for each ECG test during Cycle 3 and compared to his/her mean pretreatment QT/QTc value. The greatest change from baseline during Cycle 3 was reported. QTc prolongation is defined as a QTc exceeding 10 milliseconds (msec) with a lower 90% confidence interval (CI) exceeding 5 msec at any postdose time points per the International Conference on Harmonization (ICH) E14 guidelines for non-thorough QT studies (ICH 2005; ICH 2008). Least squares (LS) mean was calculated using a linear mixed model for repeated measures (MMRM) and adjusted for serum concentration.
Time frame: Baseline, Cycle 3 (1 cycle=21 days)
Number of Participants With Drug-Related Adverse Events (AEs)
Data presented are the number of participants who experienced treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), Grade 3 or higher TEAEs, or adverse events (AEs) leading to discontinuation of treatment that were considered to be related to ramucirumab. A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events section.
Time frame: Baseline up to data cut off (approximately 105.6 weeks)
Maximum Concentration (Cmax) During Cycle 1
Maximum observed concentration of IMC-1121B (ramucirumab) in serum during Cycle 1 (1 cycle=21 days).
Time frame: Cycle 1 [2.25 hours (h), 3.25 h, 4.25 h, 72 h, 168 h, 336 h postdose]
Maximum Concentration (Cmax) During Cycle 1, Day 4
Cmax was summarized once per cycle because participants only received 1 dose of IMC-1121B (ramucirumab) per cycle. Refer to secondary outcome measure 3 for Cmax during Cycle 1.
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ImClone Investigational Site
Providence, Rhode Island, United States
ImClone Investigational Site
Houston, Texas, United States
ImClone Investigational Site
Seattle, Washington, United States
Time frame: Approximately Week 1 (Cycle 1, Day 4)
Maximum Concentration (Cmax) During Cycle 1, Day 8
Cmax was summarized once per cycle because participants only received 1 dose of IMC-1121B (ramucirumab) per cycle. Refer to secondary outcome measure 3 for Cmax during Cycle 1.
Time frame: Approximately Week 2 (Cycle 1, Day 8)
Maximum Concentration (Cmax) During Cycle 1, Day 15
Cmax was summarized once per cycle because participants only received 1 dose of IMC-1121B (ramucirumab) per cycle. Refer to secondary outcome measure 3 for Cmax during Cycle 1.
Time frame: Approximately Week 3 (Cycle 1, Day 15)
Maximum Concentration (Cmax) During Cycle 2
Cmax was not calculated due to the sparse pharmacokinetic sampling employed on Cycle 2, Day 1.
Time frame: Cycle 2 (predose and 1.25 hours postdose)
Maximum Concentration (Cmax) During Cycle 3
The maximum observed serum concentration of IMC-1121B (ramucirumab) at steady state (Cmax,ss) during Cycle 3 (1 cycle=21 days).
Time frame: Cycle 3 [predose and 1.25 hours (h), 2.25 h, 3.25 h, 4.25 h, 72 h, 168 h, 336 h, and 504 h postdose]
Area Under Concentration (AUC) During Cycle 1
The area under the concentration versus time curve from time 0 to infinity \[AUC(0-inf)\] is reported during Cycle 1 (1 cycle=21 days).
Time frame: Cycle 1 [2.25 hours (h), 3.25 h, 4.25 h, 72 h, 168 h, 336 h postdose]
Area Under Concentration (AUC) During Cycle 1, Day 4
AUC was summarized once per cycle because participants only received 1 dose of IMC-1121B (ramucirumab) per cycle. Refer to secondary outcome measure 9 for AUC during Cycle 1 (Day 1 through Day 15).
Time frame: Approximately Week 1 (Cycle 1, Day 4)
Area Under Concentration (AUC) During Cycle 1, Day 8
AUC was summarized once per cycle because participants only received 1 dose of IMC-1121B (ramucirumab) per cycle. Refer to secondary outcome measure 9 for AUC during Cycle 1 (Day 1 through Day 15).
Time frame: Approximately Week 2 (Cycle 1, Day 8)
Area Under Concentration (AUC) During Cycle 1, Day 15
AUC was summarized once per cycle because participants only received 1 dose of IMC-1121B (ramucirumab) per cycle. Refer to secondary outcome measure 9 for AUC during Cycle 1 (Day 1 through Day 15).
Time frame: Approximately Week 3 (Cycle 1, Day 15)
Area Under Concentration (AUC) During Cycle 2, Day 1
AUC was not calculated due to the sparse pharmacokinetic sampling employed on Cycle 2, Day 1.
Time frame: Approximately Week 1 (Cycle 2, Day 1)
Area Under Concentration (AUC) During Cycle 3
The area under the concentration versus time curve over the dosing interval at steady state \[AUC(tau,ss)\] is reported during Cycle 3 (1 cycle=21 days).
Time frame: Cycle 3 [predose and 1.25 hours (h), 2.25 h, 3.25 h, 4.25 h, 72 h, 168 h, 336 h, and 504 h postdose]