Breast Cancer Clinical Trial

Phase I Dose Escalation of Oral BAY1161909 in Combination With Intravenous Paclitaxel

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.

View Full Description

Full 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.

View Eligibility Criteria

Eligibility Criteria

Inclusion Criteria:

Male or female subjects aged =/> 18 years
Subjects with advanced, histologically or cytologically confirmed advanced malignancies (solid tumors), refractory to any standard therapy, have no standard therapy available, or subjects actively refused any standard treatment and / or if, in the judgment of the investigator, experimental treatment is clinically and ethically acceptable.
For the expansion cohort: women with histologically or cytologically confirmed triple negative breast cancer (TNBC)
Subjects must have evaluable or measurable disease according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1
Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
Life expectancy of at least 12 weeks
Adequate bone marrow, liver, and renal functions

Exclusion Criteria:

Known hypersensitivity to the study drugs or excipients of the preparations or any agent given in association with this study
Evidence of peripheral neuropathy of Grade > 2
History of cardiac disease: congestive heart failure New York Heart Association (NYHA) class > II, unstable angina (anginal symptoms at rest), new-onset angina (within the past 3 months before study entry), myocardial infarction within the past 3 months before study entry, or cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers, calcium channel blockers, and digoxin are permitted)
Prior treatment with more than 3 lines of cytostatic therapies for metastatic disease unless specifically agreed between investigator and sponsor. Subjects with a history of any prior Grade =/> 3 toxicity associated with taxane treatment will be excluded.
Uncontrolled hypertension defined as systolic blood pressure >150 mmHg or diastolic blood pressure >90 mmHg, despite optimal medical management
Moderate or severe hepatic impairment, i.e. Child-Pugh class B or C
History of human immunodeficiency virus (HIV) infection.

Study is for people with:

Breast Cancer

Phase:

Phase 1

Estimated Enrollment:

69

Study ID:

NCT02138812

Recruitment Status:

Terminated

Sponsor:

Bayer

Check Your Eligibility

Let’s see if you might be eligible for this study.

What is your age and gender ?

Submit

There are 6 Locations for this study

See Locations Near You


Santa Monica California, 90403, United States

New Haven Connecticut, 06510, United States

Boston Massachusetts, 02215, United States

Detroit Michigan, 48201, United States

Nashville Tennessee, 37203, United States

San Antonio Texas, 78229, United States

How clear is this clinincal trial information?

Study is for people with:

Breast Cancer

Phase:

Phase 1

Estimated Enrollment:

69

Study ID:

NCT02138812

Recruitment Status:

Terminated

Sponsor:


Bayer

How clear is this clinincal trial information?

×

Introducing, the Journey Bar

Use this bar to access information about the steps in your cancer journey.

Please confirm you are a US based health care provider:

Yes, I am a health care Provider No, I am not a health care provider