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

NCT02138812 | Terminated Phase 1 FDA Drug

• 1 other identifier: 16804
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 6

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.

Conditions

Medical Oncology

Keywords

Phase 1; Solid tumors; Breast cancer; Paclitaxel; Mps-1 inhibitor; Taxanes

Outcome Measures

Primary Outcomes (7)

• 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 \[MTD (90)\].

  Up to 2 years

• Number of subjects with adverse events and serious adverse events as a measure of safety and tolerability.

  Up to 2 years

• Plasma concentration of Paclitaxel characterized by Cmax

  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.

• 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

  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.

• Plasma concentration of BAY1161909 characterized by Cmax

  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].

• Plasma concentration of BAY1161909 characterized by Cmax

  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.

• Plasma concentration of BAY1161909 characterized by Cmax

  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.

Other Outcomes (1)

• Tumor response evaluation following RECIST 1.1 criteria

  Up to 2 years

Study Arms (1)

BAY1161909 + Paclitaxel

EXPERIMENTAL

Participants received oral doses of BAY1161909 starting from 0.75 mg twice daily, from C1D1 onwards in a 2 days on/5 days off dosing schedule as single agent treatment in Cycle 1 (14 days), and from C2D8 onwards in a 2 days on/5 days off dosing schedule in combination with weekly intravenous paclitaxel on D1, D8, and D15 of the 28-day cycles. For single-dose Pharmacokinetic (PK) cohort: in Cycle 1, participants received a single oral dose of 6 mg BAY1161909 on C1D1 with no BAY1161909 dosing for the remainder of Cycle 1.

Drug: BAY1161909; Drug: Paclitaxel

Interventions

BAY1161909 DRUG

Given orally, with a starting dose of 0.75 mg twice daily from C1D1 onwards in a 2 days on/5 days off dosing schedule as single agent treatment in Cycle 1 (14 days), and from C2D8 onwards in a 2 days on/5 days off dosing schedule in 28-day cycles. For single-dose PK cohort: a single oral dose on C1D1

BAY1161909 + Paclitaxel

Paclitaxel DRUG

75 mg/m\^2 (initial dose escalation) or 90 mg/m\^2 (second dose escalation), weekly intravenously (IV) infusion on D1, D8, and D15 of the 28-day cycles from C2D1

BAY1161909 + Paclitaxel

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Bayer: lead

Study Sites (6)

Unknown Facility

Santa Monica, California, 90403, United States

Location

Unknown Facility

New Haven, Connecticut, 06510, United States

Location

Unknown Facility

Boston, Massachusetts, 02215, United States

Location

Unknown Facility

Detroit, Michigan, 48201, United States

Location

Unknown Facility

Nashville, Tennessee, 37203, United States

Location

Unknown Facility

San Antonio, Texas, 78229, United States

Location

Related Links

• Click here to find results for studies related to Bayer products.

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Paclitaxel

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Bayer Study Director

  Bayer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 8, 2014
• First Posted: May 15, 2014
• Study Start: May 9, 2014
• Primary Completion: April 28, 2017
• Study Completion: October 2, 2017
• Last Updated: October 12, 2018

Record last verified: 2018-10

Locations

US (6)