Phase I Study of Oral BAY 1217389 in Combination With Intravenous Paclitaxel

NCT02366949 | Completed Phase 1 FDA Drug

• 2 other identifiers: 173502014-004821-41
• Study Type: interventional
• Target: 75
• Locations: 2 countries
• Sites: 7

Brief Summary

Determine the safety, tolerability, maximum tolerated dose (MTD), and recommended Phase 2 dose (RP2D) of oral BAY1217389 given in combination with intravenous (IV) paclitaxel using an intermittent dosing schedule (2 days on / 5 days off) in subjects with advanced malignancies.

Conditions

Medical Oncology

Keywords

Phase 1; Solid tumors; Breast cancer; Paclitaxel; MPS-1 inhibitor; Oncology

Outcome Measures

Primary Outcomes (7)

• Maximum tolerated dose (MTD)

  The MTD is defined as the highest dose that can be given such that the dose-limiting toxicity (DLT) rate of the combination treatment is not more than 10% higher than the cumulative DLT rate of the standard single-agent treatment across all previous and the current cohort.

  Up to 28 days (Cycle 1)

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

  After the first study drug administration and up to 30 days after the end of treatment with study drug before primary completion analysis of the study, up to 3 years

• Maximum observed drug concentration (Cmax) of BAY1217389 in plasma

  From pre-dose up to 96 hours post-dose on C1D-8 and C1D-4; from pre-dose up to 12 hours post-dose on C1D8 and C1D9

• Area under the concentration versus time curve from zero to 12 hours (AUC [0-12]) of BAY1217389 in plasma

  From pre-dose up to 12 hours post-dose on C1D-4, C1D8 and C1D9

• Area under the concentration versus time curve from zero to 96 hours (AUC [0-96]) of BAY1217389 in plasma

  From pre-dose up to 96 hours post-dose on C1D-4

• Maximum observed drug concentration (Cmax) of paclitaxel in plasma

  From pre-dose up to 24 hours post-dose on C1D1 and C1D8

• Area under the concentration versus time curve from zero to infinity (AUC) of paclitaxel in plasma

  From pre-dose up to 24 hours post-dose on C1D1 and C1D8

Study Arms (2)

Arm 1

EXPERIMENTAL

Experimental Treatment (combination of BAY1217389 with paclitaxel in an intermittent dosing schedule) Expansion Cohort - Maximum tolerated dose of BAY1217389 and Paclitaxel

Drug: BAY1217389; Drug: Paclitaxel

Arm 2

PLACEBO COMPARATOR

Standard Treatment (Single-agent Paclitaxel )

Drug: BAY1217389; Drug: Paclitaxel

Interventions

BAY1217389 DRUG

BAY1217389 will be given orally, with a starting dose of 0.25 mg twice daily, on D1, D2, D8, D9, D15 and D16 of a 28 day cycle. BAY1217389 will be dosed in combination with paclitaxel in Arm 1 (Experimental Treatment) and from Cycle 2 onwards in Arm 2 (Standard Treatment). After Maximum tolerated dose (MTD) has been defined, expansion cohorts will be conducted at the MTD dose of BAY1217389 and paclitaxel following an intermittent dosing schedule as defined in the dose escalation phase. Up to 12 to 15 breast cancer (triple negative) subjects are planned to be enrolled in the expansion cohort. In a higher dose level Cohort 4 \> (or equal to) a relative bioavailability assessment of BAY1217389 liquid capsule formulation compared to BAY1217389 oral solution will be performed.

Arm 1; Arm 2

Paclitaxel DRUG

Paclitaxel will be given once per week IV at 90 mg/m\^2 on D1, D8, and D15 of a 28 day cycle. Paclitaxel will be dosed as a single-agent in Cycle 1 of Arm 2 (Standard Treatment Arm), and in combination with BAY1217389 in Arm 1 (Experimental Treatment Arm) and from Cycle 2 onwards in Arm 2 (Standard Treatment Arm). After Maximum tolerated dose (MTD) has been defined, expansion cohorts will be conducted at the MTD dose of BAY1217389 and paclitaxel following an intermittent dosing schedule as defined in the dose escalation phase. Up to 12 to 15 breast cancer (triple negative) subjects are planned to be enrolled in the expansion cohort.

Arm 1; Arm 2

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.
• Study population:
• For the dose-escalation cohorts: Subjects with histologically or cytologically confirmed advanced malignancies (solid tumors), refractory to any standard therapy, have no standard therapy available
• For the expansion cohort: Subjects with advanced, histologically or cytologically confirmed triple-negative breast cancer (TNBC), 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 acceptable.
• 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).
• 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), hepatitis B or hepatitis C infection.

Sponsors & Collaborators

• Bayer: lead

Study Sites (7)

Unknown Facility

Santa Monica, California, 90403, United States

Location

Unknown Facility

Denver, Colorado, 80262, United States

Location

Unknown Facility

New Haven, Connecticut, 06520, United States

Location

Unknown Facility

Hackensack, New Jersey, 07601-1991, United States

Location

Unknown Facility

Houston, Texas, 77030, United States

Location

Unknown Facility

San Antonio, Texas, 78229-3307, United States

Location

Unknown Facility

Rotterdam, 3075 EA, Netherlands

Location

Related Links

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MeSH Terms

Conditions

Breast Neoplasms; Neoplasms

Interventions

Paclitaxel

Condition Hierarchy (Ancestors)

Neoplasms by Site; 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: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 12, 2015
• First Posted: February 19, 2015
• Study Start: February 27, 2015
• Primary Completion: March 30, 2018
• Study Completion: April 18, 2019
• Last Updated: April 7, 2020

Record last verified: 2020-04

Locations

US (6); NL (1)