Open Label Study of BAY1082439 in Patients With Advanced Cancer

An Open-label Phase I Dose-escalation Study to Characterize the Safety, Tolerability, Pharmacokinetics, and Maximum Tolerated Dose of BAY 1082439 Given Once Daily Continuously or in an Intermittent Dosing Schedule in Subjects With Advanced Malignancies

The purpose of this study is to determine the safety, tolerability and the pharmacokinetics of BAY1082439

Study Overview

• Status: Completed
• Conditions: Neoplasms
• Intervention / Treatment: Drug: BAY1082439

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
  • Seoul, Korea, Republic of, 120-752
• Singapore
  • Singapore, Singapore, 119228
  • Singapore, Singapore, 169610
• Taiwan
  • Taipei, Taiwan, 10002

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects with advanced, histologically or cytologically confirmed solid tumors, refractory to any standard therapy, have no standard therapy available, or subjects must have actively refused any treatment which would be regarded standard, and / or if in the judgment of the investigator, experimental treatment is clinically and ethically acceptable

  • Expansion phase only: Subjects with histologically or cytologically confirmed, locally advanced or metastatic endometrial cancer or breast cancer or iNHL, who are refractory to or have exhausted all available therapies
• International normalized ratio (INR) and partial thromboplastin time (PTT) <1.5 x ULN [Subjects on anticoagulation with an agent such as coumadin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in these parameters exists.] For subjects on warfarin, close monitoring of at least weekly evaluations will be performed until INR is stable based on a measurement at pre-dose, as defined by the local standard of care
• Measurable or evaluable disease
• Life expectancy of at least 12 weeks
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Adequate bone marrow, liver and renal function

Exclusion Criteria:

• 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 prior to the first dose of study drug), myocardial infarction within the past 6 months prior to the first dose of study drug, or cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted)
• Uncontrolled hypertension defined as systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg, despite optimal medical management
• History of diabetes mellitus or gestational diabetes mellitus
• Fasting blood glucose level >125 mg/dL or HbA1c 7% at screening
• Active clinically serious infections > Grade 2
• History of organ allograft
• Seizure disorder requiring therapy (such as steroids or anti-epileptics)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1	Drug: BAY1082439; BAY1082439 will be given orally once daily with a 21 days cycle. Dose will be started from 15mg.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of participants with adverse events as a measure of safety and tolerability	Up to 2 years
Maximum tolerated dose of BAY1082439	Up to 1 year
Maximum observed plasma concentration (Cmax) of BAY1082439 after a single dose	Serial PK samples will be selected during cycle 1 day 1 (pre-dose and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours post-dose) and sparse samples during the rest of the cycle as well as in cycle 2
Time to Cmax (tmax) of BAY1082439 after a single dose	Serial PK samples will be selected during cycle 1 day 1 (pre-dose and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours post-dose) and sparse samples during the rest of the cycle as well as in cycle 2
Area under the plasma concentration-time curve (AUC[0-t]) of BAY1082439 after a single dose	Serial PK samples will be selected during cycle 1 day 1 (pre-dose and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours post-dose) and sparse samples during the rest of the cycle as well as in cycle 2

Secondary Outcome Measures

Outcome Measure	Time Frame
Area under the concentration-time curve over the dosing interval (AUC[0-tau])	PK parameters following single and repeat-dose administration in cycle 1
Maximum observed concentration (Cmax)	PK parameters following single and repeat-dose administration in cycle 1
Time of occurrence of Cmax (tmax)	PK parameters following single and repeat-dose administration in cycle 1
Terminal phase half-life (t1/2)	PK parameters following single and repeat-dose administration in cycle 1
Tumor response based on Response Evaluation Criteria in Solid Tumors, Version 1.1	Up to 2 years

Collaborators and Investigators

• Sponsor: Bayer

Study record dates

Study Major Dates

• Study Start (Actual): November 21, 2012
• Primary Completion (Actual): June 3, 2016
• Study Completion (Actual): February 6, 2017

Study Registration Dates

• First Submitted: November 7, 2012
• First Submitted That Met QC Criteria: November 14, 2012
• First Posted (Estimate): November 19, 2012

Study Record Updates

• Last Update Posted (Actual): January 30, 2018
• Last Update Submitted That Met QC Criteria: January 29, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Other Study ID Numbers: 15734

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No