Terminated/Withdrawn

Medical Oncology

Bayer Identifier:

16804

ClinicalTrials.gov Identifier:

NCT02138812

EudraCT Number:

Not Available

EU CT Number:

Not Available

Phase I dose escalation of oral BAY1161909 in combination with intravenous paclitaxel

Trial purpose

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.

Key Participants Requirements

Sex

Both

Age

18 - N/A

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.

Trial summary

Enrollment Goal

Trial Dates

May 2014 - October 2017

Phase

Phase 1

Could I Receive a placebo

Products

Empesertib (BAY1161909)

Accepts Healthy Volunteer

Where to participate

Status	Institution	Location
Completed		Boston, 02215, United States
Completed		Nashville, 37203, United States
Completed		Detroit, 48201, United States
Completed		San Antonio, 78229, United States
Completed		New Haven, 06510, United States
Completed		Santa Monica, 90403, United States

Primary Outcome

Maximum tolerated dose (MTD)
MTD is defined as the highest dose of oral BAY1161909 (administered in combination with or without IV paclitaxel) that can be given such that not more than 30% of the subjects experience a dose-limiting toxicity (DLT) during Cycles 1 and 2. The safety profile of oral BAY1161909 will first be determined in combination with 75 mg/m^2 IV paclitaxel [MTD (75)]. Starting in >Cohort 7 (12 mg 2 times daily [BID] BAY1161909) the MTD of oral BAY1161909 will then be refined for the combination with 90 mg/m^2 IV paclitaxel [MTD (90)].
Time Frame:
Up to 2 years
Safety Issue:
Yes
Number of subjects with adverse events and serious adverse events as a measure of safety and tolerability.
Time Frame:
Up to 2 years
Safety Issue:
Yes
Plasma concentration of Paclitaxel characterized by Cmax
Time Frame:
C2D1 (without oral BAY1161909): pre-dose and 0.5,1,2,3,4,6,8,12,24 (C2D2) & 48hrs (C2D3) after the start of IV infusion on C2D1. C2D8 (with oral BAY1161909): pre-dose and 0.5,1,2,3,4,6, 8,12,24 (C2D9) & 48hrs (C2D10) after the start of infusion on C2D8.
Safety Issue:
Yes
Plasma concentration of BAY1161909 characterized by Cmax
C1D1 (single-dose PK without IV paclitaxel), C1D2 (multiple-dose PK without IV paclitaxel; no ED on C1D2, MD=Morning Dose, ED= Evening Dose
Time Frame:
C1D1: pre-dose & 0.5,1,2,3,4,6,8,12 hrs after the MD on C1D1 [12-hour sample to be collected before administration of the ED]. C1D2: pre-dose & 0.5,1,2,3,4,6,8,12, 24 (C1D3), 48 (C1D4), 72 (C1D5) & 144 hrs (C1D8 pre-dose) after the MD on C1D2.
Safety Issue:
Yes
Plasma concentration of BAY1161909 characterized by Cmax
Time Frame:
C2D8 (single-dose PK with IV paclitaxel): pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12 hours after the morning dose on C2D8 [12-hour sample to be collected before administration of the evening dose].
Safety Issue:
Yes
Plasma concentration of BAY1161909 characterized by Cmax
Time Frame:
C1D1 (single-dose PK cohort only): pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (C1D2), 48 (C1D3), 72 (C1D4), 96 (C1D5), 168 (C1D8), 240 (C1D11) and 336 hours (before C2D1 IV paclitaxel administration) after the morning dose on C1D1.
Safety Issue:
Yes
Plasma concentration of BAY1161909 characterized by Cmax
Time Frame:
C1D-7 (relative bioavailability assessment subjects): pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (C1D-6), and 72 (C1D-4) hours after the single dose on C1D-7.
Safety Issue:
Yes

Trial design

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

Trial Type

Interventional

Intervention Type

Drug

Trial Purpose

Treatment

Allocation

N/A

Blinding

Open Label

Assignment

Single Group Assignment

Trial Arms

Additional Information

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