A Phase Ib Study to Evaluate Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Clinical Activity of the Oral AKT Inhibitor GSK2110183 Administered in Combination With Bortezomib and Dexamethasone in Subjects With Relapsed/Refractory Multiple Myeloma
This is a Phase Ib, open-label study to evaluate the safety, tolerability, pharmacokinetics
(PK), pharmacodynamics (PD) and clinical activity of GSK2110183 dosed in combination with
bortezomib and dexamethasone in relapsed/refractory multiple myeloma (MM) subjects who have
failed at least one line of systemic treatment. Part 1 will identify the maximum tolerated
dose(s) (MTD) of the combination regimen.
Part 1, Schedule A will assess the safety and pharmacodynamics of GSK2110183 administered
once daily with bortezomib (1.3 mg/m2) and dexamethasone (20 mg) given biweekly. It is
estimated that up to 35-45 evaluable subjects will be enrolled in Part 1. Part 2 will
explore further the safety, tolerability, pharmacokinetics, pharmacodynamics and clinical
activity of the MTD(s) identified in Part 1. A minimum of 15 and maximum of 40 subjects
will enroll in Part 2 Safety/Clinical Activity Cohort for each Schedule explored. The Part
2 PK/PD cohort will enroll up to 18 subjects. This pharmacokinetic cohort will explore
whether exposure to GSK2110183 at the MTD is similar when GSK2110183 is administered alone
or in combination with bortezomib and dexamethasone. The same relationship will be explored
for bortezomib and dexamethasone when the two drugs are given by themselves or in
combination with GSK2110183. The identified MTD(s) and pharmacodynamic results in this study
will inform the doses for future development of the regimen of GSK2110183 dosed in
combination with bortezomib and dexamethasone in subjects with relapsed/refractory MM.
Interventional
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
The recommended Phase II dose (RP2D) and schedule of GSK2110183, bortezomib and dexamethasone dosed in combination.
Dose and schedule determined using adverse events and changes in safety assessments (laboratory parameters, vital signs and ECG parameters). Recommended Phase 2 Dose (RP2D) will be defined in Part 1. The specific number of subjects to be enrolled is dependent on the number of dose limiting toxicities (DLTs) reported; enrollment of up to 45 subjects in Part 1 is estimated. Subjects will continue on study from the date of randomization until the date of the first documented disease progression or when the subject meets one of the Treatment Discontinuation criteria, whichever comes first
Estimation is that each subject may be assessed for up to 48 months.
Yes
GSK Clinical Trials
Study Director
GlaxoSmithKline
Ireland: Irish Medicines Board
115125
NCT01428492
March 2012
September 2013
Name | Location |
---|---|
GSK Investigational Site | Phoenix, Arizona 85013 - 4496 |
GSK Investigational Site | Bakersfield, California 93309 |
GSK Investigational Site | Raleigh, North Carolina 27609 |
GSK Investigational Site | Akron, Ohio 44304 |
GSK Investigational Site | Green Bay, Wisconsin 54301 |
GSK Investigational Site | Savannah, Georgia 31405 |
GSK Investigational Site | Park Ridge, Illinois 60068 |
GSK Investigational Site | New York, New York 10021 |