Ignite Creation Date:
2025-12-25 @ 3:04 AM
Ignite Modification Date:
2025-12-26 @ 1:43 AM
Study NCT ID:
NCT01138033
Status:
COMPLETED
Last Update Posted:
2017-05-11
First Post:
2010-06-03
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Study of a Focal Adhesion Kinase Inhibitor in Subjects With Solid Tumors
Sponsor:
GlaxoSmithKline
Organization:
Study Overview
Official Title:
A Phase I Open-Label Dose Escalation Study of the Focal Adhesion Kinase Inhibitor, GSK2256098, in Subjects With Solid Tumors
Status:
COMPLETED
Status Verified Date:
2017-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study is a Phase I dose escalation study in subjects with solid tumors. Part 1 will identify the maximum tolerated dose (MTD) using a dose-escalation procedure. Following identification of the MTD, enrollment into Parts 2, 3, 4 and 5 may be concurrent. Part 2 will explore further the safety, PK, tolerability, and anti-tumor activity of GSK2256098 in subjects with tumors known to overexpress focal adhesion kinase (FAK). Part 3 will characterize the range of biologically effective doses by assessing pharmacodynamic (PD) markers in hair, skin and tumor tissue at doses that will not go lower than 80 mg or above the MTD dose levels tested during the Phase 1 dose escalation. Part 4 will explore further the safety, PK, tolerability and anti-tumor activity of GSK2256098 in subjects with relapsed glioblastoma multiforme (GBM). The primary objective of this study is to determine the safety, tolerability, and MTD of GSK2256098. Secondary objectives are to characterize the pharmacokinetics (PK) of GSK2256098; to identify a range of biologically active doses; to explore the anti-tumor activity of GSK2256098, and to explore relationships between GSK2256098 PK, PD and clinical endpoints. Part 5 will investigate the time course, the extent of an apparent change in the PK of GSK2256098 following repeated dosing, and screen for potential CYP3A induction as a possible mechanism of reduced systemic exposure of GSK2256098 at Day 15 and later time points. The primary objective of this study is to determine the safety, tolerability, and MTD of GSK2256098.
Detailed Description:
This study is a Phase I dose escalation study in subjects with solid tumors. Part 1 will identify the maximum tolerated dose (MTD) using a dose-escalation procedure. Following identification of the MTD, enrollment into Parts 2, 3, 4, and 5 may be concurrent. Part 2 will explore further the safety, PK, tolerability, and anti-tumor activity of GSK2256098 in subjects with tumors known to overexpress focal adhesion kinase (FAK). Part 3 will characterize the range of biologically effective doses by assessing pharmacodynamic (PD) markers in hair, skin and tumor tissue at doses that will not go lower than 80 mg or above the MTD dose levels tested during the Phase 1 dose escalation. Part 4 will explore further the safety, PK, tolerability and anti-tumor activity of GSK2256098 in subjects with relapsed glioblastoma multiforme (GBM). The primary objective of this study is to determine the safety, tolerability, and MTD of GSK2256098. Secondary objectives are to characterize the pharmacokinetics (PK) of GSK2256098; to identify a range of biologically active doses; to explore the anti-tumor activity of GSK2256098, and to explore relationships between GSK2256098 PK, PD and clinical endpoints.
Subjects with solid tumors will receive GSK2256098 orally without interruption on consecutive days. The planned starting dose in Part 1 will be a total daily dose of 160 mg administered as 80 mg twice daily (BID) during the repeat dose phase of the study. In the first cohort, administration of study drug will be initiated as a single dose (80 mg) on Day 1 that will be followed by collection of PK samples. Subjects may then begin repeat dosing (80 mg BID) on Day 2 following the collection of the 24-h PK sample. In subsequent cohorts, administration of study drug will be given as a single dose (half the total daily dose) on Day 1 followed by collection of PK samples. Subjects may begin repeat dosing on Day 2 following collection of the 24-h PK sample.
During dose escalation (Part 1), a modified accelerated dose titration design will be followed by a standard 3+3 dose escalation design until the MTD is established. After the MTD is established approximately 30 additional subjects with tumors reported to have FAK over-expression will be enrolled to further explore the safety, tolerability and clinical activity of GSK2256098 (Part 2). Additional cohorts below the MTD may be expanded to further explore and characterize the range of biologically effective doses (Part 3). Part 4 will further explore the safety, PK, tolerability and anti-tumor activity of GSK2256098 in subjects with relapsed glioblastoma multiforme (GBM). Part 5 will investigate the time course, the extent of an apparent change in the PK of GSK2256098 following repeated dosing, and screen for potential CYP3A induction as a possible mechanism of reduced systemic exposure of GSK2256098 at Day 15 and later time points. The primary objective of this study is to determine the safety, tolerability, and MTD of GSK2256098.
Subjects with solid tumors will receive GSK2256098 orally without interruption on consecutive days. The planned starting dose in Part 1 will be a total daily dose of 160 mg administered as 80 mg twice daily (BID) during the repeat dose phase of the study. In the first cohort, administration of study drug will be initiated as a single dose (80 mg) on Day 1 that will be followed by collection of PK samples. Subjects may then begin repeat dosing (80 mg BID) on Day 2 following the collection of the 24-h PK sample. In subsequent cohorts, administration of study drug will be given as a single dose (half the total daily dose) on Day 1 followed by collection of PK samples. Subjects may begin repeat dosing on Day 2 following collection of the 24-h PK sample.
During dose escalation (Part 1), a modified accelerated dose titration design will be followed by a standard 3+3 dose escalation design until the MTD is established. After the MTD is established approximately 30 additional subjects with tumors reported to have FAK over-expression will be enrolled to further explore the safety, tolerability and clinical activity of GSK2256098 (Part 2). Additional cohorts below the MTD may be expanded to further explore and characterize the range of biologically effective doses (Part 3). Part 4 will further explore the safety, PK, tolerability and anti-tumor activity of GSK2256098 in subjects with relapsed glioblastoma multiforme (GBM). Part 5 will investigate the time course, the extent of an apparent change in the PK of GSK2256098 following repeated dosing, and screen for potential CYP3A induction as a possible mechanism of reduced systemic exposure of GSK2256098 at Day 15 and later time points. The primary objective of this study is to determine the safety, tolerability, and MTD of GSK2256098.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: