Study of PI3 Kinase/mTOR Inhibitor BEZ235 Twice Daily for Advanced Solid Tumors
This is a dose escalation trial to evaluate twice daily dosing of the sachet formulation of BEZ235. This trial will find the maximum tolerated dose (MTD) of the sachet formulation given twice daily, as well as evaluate pharmacokinetics (PK) and pharmacodynamics (PD) of the twice daily dosing. Patients will initially be given once daily dosing to determine the PK and PD of the single daily dose. On Day 9, they will begin twice daily dosing, with half of the single daily dose divided twice daily, and PK and PD of the twice daily dose will be determined.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I PK/PD Study of the PI3 Kinase/mTOR Inhibitor BEZ235 Given Twice Daily for the Treatment of Patients With Advanced Solid Tumors|
- Maximum tolerated dose of BEZ235 given twice daily [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]To determine the maximum tolerated dose (MTD) of BEZ235 given twice daily in patients with advanced solid tumors
- To describe the toxicities of this regimen [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
The safety endpoints to be summarized are:
- Incidence of dose-limiting toxicities (DLTs)
- Incidence of adverse events (AEs)
- Incidence of grade 1, grade 2, grade 3 and grade 4 AEs
- Incidence of serious adverse events (SAEs)
- Clinical Efficacy [ Time Frame: 18 months ] [ Designated as safety issue: No ]To describe the clinical efficacy of this regimen in patients with advanced solid tumors. The tumor response will be measured by the number of patients with complete responses, partial responses, stable disease and progressive disease.
- PK profile of BEZ235 [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
To characterize the PK profile of BEZ235 given as a twice daily dose. The PK parameters (including AUC (0-∞), AUC (0-t), Cmax, tmax, λz, and t½) of BEZ235 following oral administration will be assessed by analysis of BEZ235 plasma concentrations using a non-compartmental approach.
During treatment PK blood samples will be taken at the following timepoints:
- Cycle 1, Day 1: pre-dose, 1, 2, 4, 8, 10, 12 and 24 hours post-dose
- Cycle 1, Day 8: pre-dose, 1, 2, 4, 8, 10, 12 and 24 hours post-dose
- Cycle 1, Day 28: pre-dose, and at 1, 2, 4, 8, 10, 12 and 24 hours post-dose
|Study Start Date:||April 2011|
|Study Completion Date:||January 2014|
|Primary Completion Date:||January 2014 (Final data collection date for primary outcome measure)|
BEZ235 will be given on a dose-escalation design, beginning at 200 mg BID (SDS sachet) in 3 patients and progressing to 400 mg, 600 mg, and 800 mg respectively based on tolerability.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01343498
|United States, Oklahoma|
|Oklahoma City, Oklahoma, United States, 71304|
|United States, Tennessee|
|Nashville, Tennessee, United States, 37203|
|Study Chair:||Johanna C Bendell, M.D.||SCRI Development Innovations, LLC|