A Phase 1 Study for the Evaluation of Excretion (Mass Balance) and Pharmacokinetics of 14C-Labeled Belinostat in Patients With Advanced Cancer
This is a Phase 1, open-label, single-dose study of 14C-labeled belinostat to determine
routes of elimination of belinostat. A single dose of 14C-labeled belinostat (approximately
94.3 to 105 µCi, 1500 mg) will be administered as a 30-minute IV infusion to the patient.
Routes of elimination of belinostat and its metabolites will be assessed by estimating the
recovery of total radioactivity and parent belinostat over a period of 7 days. Plasma
samples will be taken for 3 days at specified intervals for PK assessments. Total
radioactivity in plasma, urine, and feces will be determined by liquid scintillation
counting. Concentrations of belinostat in plasma and urine will be determined using a
validated liquid chromatography - tandem mass spectroscopy (LC-MS/MS) method. Selected
plasma, urine, and feces samples will be retained for use in the metabolism investigation.
Samples will be initially analyzed using radio-high performance liquid chromatography (HPLC)
to determine the number and relative proportion of belinostat and metabolites present.
Selected samples will be subsequently analyzed using LC-MS to identify the major metabolites
(> 10% of parent area under the curve [AUC]). If it is in the interest of the patient,
treatment with non-radiolabeled belinostat may be continued with 21-day cycles until disease
progression, initiation of new anticancer therapy, or an adverse event (AE) that may affect
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum recovery of the radioactive dose in urine and feces
The route of elimination of belinostat will be determined by the recovery of total radioactivity (parent drug and metabolites) and unmetabolized belinostat in urine and feces following single IV administration of 14C-labeled belinostat in patients with recurrent or progressive malignancy.
Emiliano Calvo, MD
Hospital Universitario Madrid Sanchinarro
United States: Food and Drug Administration