Ignite Creation Date:
2025-12-26 @ 11:13 PM
Ignite Modification Date:
2025-12-26 @ 11:13 PM
Study NCT ID:
NCT02138812
Status:
TERMINATED
Last Update Posted:
2018-10-12
First Post:
2014-05-08
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Phase I Dose Escalation of Oral BAY1161909 in Combination With Intravenous Paclitaxel
Sponsor:
Bayer
Organization:
Study Overview
Official Title:
An Open-label Phase I Dose-escalation Study to Characterize the Safety, Tolerability, Pharmacokinetics, and Maximum Tolerated Dose of Oral BAY1161909 in Combination With Weekly Intravenous Paclitaxel Given in an Intermittent Dosing Schedule in Subjects With Advanced Malignancies
Status:
TERMINATED
Status Verified Date:
2018-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
As another Mps1 inhibitor was being developed in parallel, the strategic decision was to move forward with the development of the follow up compound only.
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Determine the safety, tolerability, maximum tolerated dose (MTD), and recommended Phase II dose (RP2D) of BAY1161909 in combination with paclitaxel in subjects with advanced malignancies.
Detailed Description:
BAY1161909 is a potent and highly selective inhibitor of monopolar spindle 1 (Mps1) kinase activity. Human Mps1 is a serine threonine kinase which functions as a core component of the spindle assembly checkpoint (SAC), a key surveillance mechanism that monitors the attachment of spindle microtubules to the kinetochores of the chromosomes during pro-metaphase and halts the transitions to anaphase until all chromosomes are bi-oriented, fully attached, and correctly tensed at the metaphase plate. Mps1 is expressed in the mitosis phase of the cell cycle in proliferating cells. Overexpression of Mps1 has been observed in several cancer cell lines and tumor types including lung and breast cancers.
Established anti-mitotic drugs such as vinca alkaloids, taxanes, or epothilones activate the SAC either by destabilizing or stabilizing spindle microtubules resulting in mitotic arrest. Prolonged arrest in mitosis forces a cell either into a mitotic exit without cytokinesis or into a mitotic catastrophe leading to cell death. In contrast, Mps1 inhibitors inactivate the SAC and accelerate progression of cells through mitosis eventually resulting in severe chromosomal missegregation, mitotic catastrophe, and cell death. Consequently, Mps1 inhibition leads to failure of cells to arrest in mitosis in response to anti-mitotic drugs. Thus, the combination of microtubule-interfering agents and Mps1 inhibition strongly increases chromosomal segregation errors and cell death and therefore, constitutes an efficient strategy for selectively eliminating tumor cells.
This study will attempt to answer the following questions:
* What are the side effects of BAY1161909 when given at different dose levels and schedules with paclitaxel?
* What dose level and schedule of BAY1161909 should be tested in future clinical research studies?
* How much BAY1161909 and paclitaxel is in the blood at specific times after administration?
* Does the treatment with BAY1161909 with paclitaxel show any effect on the tumor growth?
* Are there specific biomarkers that might be able to explain why some patients respond to treatment and others do not.
Established anti-mitotic drugs such as vinca alkaloids, taxanes, or epothilones activate the SAC either by destabilizing or stabilizing spindle microtubules resulting in mitotic arrest. Prolonged arrest in mitosis forces a cell either into a mitotic exit without cytokinesis or into a mitotic catastrophe leading to cell death. In contrast, Mps1 inhibitors inactivate the SAC and accelerate progression of cells through mitosis eventually resulting in severe chromosomal missegregation, mitotic catastrophe, and cell death. Consequently, Mps1 inhibition leads to failure of cells to arrest in mitosis in response to anti-mitotic drugs. Thus, the combination of microtubule-interfering agents and Mps1 inhibition strongly increases chromosomal segregation errors and cell death and therefore, constitutes an efficient strategy for selectively eliminating tumor cells.
This study will attempt to answer the following questions:
* What are the side effects of BAY1161909 when given at different dose levels and schedules with paclitaxel?
* What dose level and schedule of BAY1161909 should be tested in future clinical research studies?
* How much BAY1161909 and paclitaxel is in the blood at specific times after administration?
* Does the treatment with BAY1161909 with paclitaxel show any effect on the tumor growth?
* Are there specific biomarkers that might be able to explain why some patients respond to treatment and others do not.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: