This study will investigate clinical activity, safety, and tolerability of the anti-angiogenic compound cilengitide (EMD 121974) in the treatment of first recurrence of glioblastoma multiforme (GBM).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
81
Subjects will receive 1-hour intravenous infusion of 500 mg cilengitide twice weekly on Day 1 and 4 of each week during every 4-week cycle, for a total of 8 infusions per cycle. Cycles were repeated without pause until progressive disease (PD), unacceptable adverse events (AEs), or withdrawal of consent.
Subjects will receive 1-hour intravenous infusion of 2000 mg cilengitide twice weekly on Day 1 and 4 of each week during every 4-week cycle, for a total of 8 infusions per cycle. Cycles were repeated without pause until progressive disease (PD), unacceptable adverse events (AEs), or withdrawal of consent.
University of Alabama at Birmingham
Birmingham, Alabama, United States
Barrow Neurological Institute
Phoenix, Arizona, United States
Percentage of Subjects With Progression-free Survival
Progression-free survival was defined as subjects who survived greater than or equal to (\>=) 180 days without disease progression. Disease progression was assessed as per independent central blinded radiology assessment.
Time frame: Month 6
Percentage of Subjects With Overall Response Rate
Overall response rate was defined as percentage of subjects who had best response during the study which was either complete response (CR: disappearance of all tumors, no new lesions and stable or improved neurological examination) or partial response (PR: \>= reduction in the sum of the products of the largest perpendicular diameters compared to the baseline sum, no worsening of evaluable lesion and stable or improved neurological examination). CR or PR was confirmed within 31 days with a repeat neuroimaging.
Time frame: From the start of treatment up to 6 years
Time to Disease Progression
Time to disease progression was defined as the number of days between the first dose and the date of first assessment of progressive disease during the study or until death. Surviving subjects without progressive disease were censored at the time of the last visit and the subject was known to be non-progressing. Disease progression was assessed as per independent central blinded radiology assessment.
Time frame: From the start of treatment until disease progression (assessed up to a maximum of 6 years)
Overall Survival Time
Survival time was defined as the number of months between the date of randomization and the date of death or the last date the subject was known to be alive.
Time frame: From the start of treatment until death (assessed up to a maximum of 6 years)
Percentage of Subjects With 1-year of Survival Rate
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UCLA Medical Center
Los Angeles, California, United States
Denise Damek
Aurora, Colorado, United States
Northwestern University
Chicago, Illinois, United States
Indiana University Medical Center
Indianapolis, Indiana, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
University of Massachusetts
Worcester, Massachusetts, United States
Henry Ford Health System
Detroit, Michigan, United States
Washington University
St Louis, Missouri, United States
...and 7 more locations
1-year survival rate was defined as percentage of subjects who survived for \>=365 days with or without disease progression. Disease progression was assessed as per independent central blinded radiology assessment.
Time frame: From the start of treatment up to 1 year
Maximum Observed Plasma Concentration (Cmax)
Cmax is the maximum observed plasma concentration of cilengitide after administration.
Time frame: Pre-dose, 1, 1.5, 2, 3, 4, 8, 24 hours post-infusion on Day 1 of Week 1 in Cycle 1 and 2
Time to Reach Maximum Plasma Concentration (Tmax)
Tmax is the time to reach the maximum plasma concentration (Cmax) of cilengitide.
Time frame: Pre-dose,1,1.5,2,3,4,8 and 24 hours post-infusion on Day 1 of Week 1 in Cycles 1 and 2
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity After Administration (AUC 0-infinity)
AUC 0-infinity is the area under the curve for the plot showing plasma concentration against time from time zero to the time of the last quantifiable concentration of cilengitide.
Time frame: Pre-dose,1,1.5,2,3,4,8 and 24 hours post-infusion on Day 1 of Week 1 in Cycles 1 and 2
Apparent Terminal Rate Constant (Lambda z)
Lambda z was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression on terminal data points of the curve.
Time frame: Pre-dose,1,1.5,2,3,4,8 and 24 hours post-infusion on Day 1 of Week 1 in Cycles 1 and 2
Terminal Half-life (t1/2)
The t1/2 is the time taken to eliminate half the amount of cilengitide.
Time frame: Pre-dose,1,1.5,2,3,4,8 and 24 hours post-infusion on Day 1 of Week 1 in Cycles 1 and 2
Mean Residence Time of Drug in the Body (MRT)
MRT is defined as the mean duration of time a drug molecule is present in the systemic circulation.
Time frame: Pre-dose,1,1.5,2,3,4,8 and 24 hours post-infusion on Day 1 of Week 1 in Cycles 1 and 2
Total Body Clearance (CL) of Drug From Plasma/Cerebro Spinal Fluid (CSF)
CL is a quantitative measure of the rate at which a drug substance is removed from the body, calculated as dose divided by AUC0-infinity.
Time frame: Pre-dose,1,1.5,2,3,4,8 and 24 hours post-infusion on Day 1 of Week 1 in Cycles 1 and 2
Apparent Volume of Distribution During the Terminal Phase (Vz)
Vz was calculated as Dose/(AUC0-infinity multiplied by elimination rate constant \[lambda z\]) following single dose.
Time frame: Pre-dose,1,1.5,2,3,4,8 and 24 hours post-infusion on Day 1 of Week 1 in Cycles 1 and 2
Apparent Volume of Distribution at Steady State (Vss)
Vss is the theoretical volume that the total amount of administered drug would have to occupy (if it were uniformly distributed), to provide the same concentration as it is in blood plasma at steady state.
Time frame: Pre-dose, 1, 1.5, 2, 3, 4, 8, 24 hours post-infusion on Day 1 of Week 1 in Cycle 1 and 2
Number of Subjects With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
An AE was any untoward medical occurrence in a subject which did not necessarily have a causal relationship with the study drug. A TEAE was any AE that started on or any time after the day of first dose of cilengitide during the treatment phase or within the safety follow-up after last dose of cilengitide. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening; persistent or significant disability/incapacity; congenital anomaly.
Time frame: From the start of treatment up to 6 years