A Study of GSK2110183 in Subjects With Proteasome Inhibitor Refractory Multiple Myeloma
Status:
Withdrawn
Trial end date:
2011-11-01
Target enrollment:
Participant gender:
Summary
This is a single arm, open-label, Phase Ib/II study to evaluate the safety, pharmacokinetics,
pharmacodynamics, and efficacy of the oral AKT inhibitor, GSK2110183, when administered to
subjects with proteasome inhibitor refractory multiple myeloma (MM). During Part 1 of the
study, GSK2110183 will be administered to subjects in sequential Pharmacokinetic (PK) Cohorts
on a continuous daily dosing schedule in 21-day cycles until one of the Treatment
Discontinuation Criteria is met. The PK Cohorts will characterize the PK of GSK2110183 in
plasma and urine as well as determine the Recommended Phase 2 Dose (RP2D) of GSK2110183. The
RP2D will be that dose that provides adequate PK exposure and biologic activity without
exceeding the maximum tolerated dose (MTD) in MM subjects as defined in the current study. In
Part 2 of the study, the RP2D will be further evaluated using a flexible 2-stage design with
a stopping rule to allow for early termination based on lack of efficacy at the end of Stage
1. The first stage will accrue 20 subjects who will receive GSK2110183 at the RP2D. If a
clinical response is observed in at least 1 subject in Stage 1, the study will proceed to
Stage 2 and 20 additional subjects will be enrolled. GSK2110183 will be administered in Part
2 (Stage 1 and Stage 2) on a continuous daily dosing schedule in 21 day cycles until
International Myeloma Working Group criteria for progression are met, at which point the
subject will proceed to GSK 2110183 + bortezomib salvage therapy provided they meet the
additional eligibility criteria for this phase of the study. GSK2110183 and bortezomib will
be continued until one of the Treatment Discontinuation Criteria is met.
Exploratory PK/PD analyses may be performed to examine the potential relationships between
GSK2110183 pharmacokinetics and pharmacodynamic biomarkers.