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An Open-Label, Single Arm, Phase Ib/II Study of GSK2110183 in Subjects With Proteasome Inhibitor Refractory Multiple Myeloma
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.
Details
| Lead sponsor | GlaxoSmithKline |
|---|---|
| Phase | Phase 2 |
| Status | WITHDRAWN |
| Start date | 2011-11 |
| Completion | 2011-11 |
Conditions
- Cancer
Interventions
- Part 1; Cohort 1
- Part 1; Cohort 2
- Part 2; Stage 1
- Part 2, Stage 2
Primary outcomes
- Evaluate the safety and tolerability of GSK2110183 in subjects with proteasome inhibitor refractory MM. — Subjects will continue on the study from the date of randomization until the date of the first documented progression or when the subjects meet one of the Treatment Discontinuation Criteria and may be assessed on average up to 48 months.
Subjects with proteasome inhibitor refractory MM enrolled into Parts 1 and 2 will be evaluate for safety and tolerability of GSK2110183 by the assessment of adverse events and changes from baseline in safety assessments including laboratory parameters, vital signs, and electrocardiogram (ECG) parameters. - Determine a Recommended Phase II Dose (RP2D). — Subjects will continue on the study from the date of randomization until the date of the first documented progression or when the subjects meet one of the Treatment Discontinuation Criteria and may be assessed on average up to 48 months.
RP2D is defined as a dose that provides adequate pharmacokinetics exposure and biologic activity without exceeding the Maximum Tolerated Dose (MTD) in Multiple Myeloma (MM) subjects as defined in the current study. RP2D will be defined in Part 1 of the study. The specific number of subjects to be enrolled is dependent on the number of Dose Limiting Toxicities (DLTs) reported; however, enrollment of approximately 18 subjects is estimated. The RP2D chosedn in Part 1 will be the dosing regimen used in Part 2. - Assess the clinical activity of GSK2110183 in subjects with proteasome inhibitor refractory MM. — Subjects will continue on the study from the date of randomization until the date of the first documented progression or when the subjects meet one of the Treatment Discontinuation Criteria and may be assessed on average up to 48 months.
Subjects enrolled into Parts 1 and 2 will be assessed for overall response rate of GSK2110183 in subjects with proteasome inhibitor refractory Multiple Myeloma using the 2011 recommendations in the Report of the International Myeloma Workshop Consensus.
Countries
Australia