Effect of trabectedin on the QT interval in patients with advanced solid tumor malignancies

The primary objective of this study was to access the potential effects of trabectedin on the QT/QTc interval in patients with locally advanced or metastatic solid tumors. Patients (n = 75) who had received a parts per thousand currency sign3 previous lines of chemotherapy and had either relapsed or had progressive disease were enrolled. Patients were administered 3-h intravenous infusions of placebo (saline) on day 1 and trabectedin (1.3 mg/m(2)) on day 2. Time-matched serial triplicate ECG recordings and pharmacokinetic blood samples were collected over 24 h on both days. Heart rate corrected mean QT intervals and changes from predose baseline in QTc (Delta QTc) were assessed. The difference in Delta QTc between trabectedin and placebo was calculated at each time point (Delta Delta QTc). The upper limits of the 90% confidence interval for Delta Delta QTcF and Delta Delta QTcB at all time points were less than the prespecified noninferiority margin of 10 ms (a parts per thousand currency sign6.65 ms). No patient had a QTc > 500 ms or a time-matched increase from baseline in QTc > 60 ms at any time point. Regression analyses indicated Delta Delta QTc was poorly correlated with trabectedin concentration. No adverse events suggestive of proarrhythmic potential were reported. Trabectedin did not prolong the QTc interval. Safety and pharmacokinetic profiles of trabectedin were similar to that observed in other ovarian and breast cancer studies.