NCT01428492

Ph 1b Study to Evaluate GSK2110183 in Combination With Bortezomib and Dexamethasone in Subjects With Multiple Myeloma

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: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 90 (actual)
• Sponsor: Novartis · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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 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, tolerability and clinical activity of the MTD(s) identified in Part 1, including a pharmacokinetic cohort.

Detailed description

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.

Conditions

• Multiple Myeloma

Interventions

Type	Name	Description
DRUG	GSK2110183	The oral, once daily dose of GSK2110183 will be dependent on the cohort to which a subject is assigned. Subjects enrolled in Cohort 1 will receive 75 mg GSK2110183 once daily. Dose escalation in Schedule A and Schedule B will follow 25 mg increments in a 3+3 dose escalation procedure up to a maximum of 150mg daily or until MTD is reached, whichever comes first, for each schedule. GSK2110183 will continue at daily dosing until treatment discontinuation criteria is met.
DRUG	Bortezomib	Bortezomib (1.0 mg/m2) will be administered on days 1, 4, 8, and 11 of each 21-day cycle for cohort 1 for up to 8 cycles. Bortezomib (1.3 mg/m2) will be administered on days 1, 4, 8, and 11 of each 21-day cycle for up to 8 cycles. Bortezomib (1.5 mg/m2) will be administered on days 1, 8, and 15 of each 21-day cycle for up to 8 cycles.
DRUG	Dexamethasone	Dexamethasone will be given orally at a fixed dose of 20 mg only on days of bortezomib dosing in both Schedule A and Schedule B.

Timeline

• Start date: 2011-12-01
• Primary completion: 2015-10-01
• Completion: 2015-10-01
• First posted: 2011-09-05
• Last updated: 2018-08-08

Locations

13 sites across 5 countries: United States, Australia, Canada, Ireland, Taiwan