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

Status
Active
Cancer Type
Multiple Myeloma
Trial Phase
Phase I
Eligibility
18 and over, Male and Female
Study Type
Biomarker/Laboratory analysis
Treatment
NCD ID
NCT01428492
Protocol IDs
115125 (primary)
Study Sponsor
GlaxoSmithkline

Summary

Phase Ib, open-label study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and clinical activity of GSK2110183 dosed in combination with bortezomib and dexamethasone in 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. Schedule A - GSK2110183 administered once daily with bortezomib (1.3 mg/m2) and dexamethasone (20 mg) given biweekly. Part 2 will further explore the safety and tolerability of the MTD(s) identified in Part 1, including a pharmacokinetic cohort.

Objectives

This is a Phase Ib, open-label study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics 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.

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. Part 2 will explore further the safety, tolerability, pharmacokinetics, pharmacodynamics and clinical activity of the MTD(s) identified in Part 1 in up to 49 subjects, including up to 18 subjects enrolled to a pharmacokinetic cohort to 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.

Treatment Sites in Georgia


Winship Cancer Institute of Emory University
1365 Clifton Road NE
Building C
Atlanta, GA 30322
404-778-5180
winshipcancer.emory.edu

Study Coordinator:
Kenisha Barron
(404) 778-5144

Doctors:

Ajay K. Nooka MD, MPH