Open Label Phase I Dose Escalation Study With BAY1143572 in Patients With Advanced Cancer

An Open-label Phase I Dose-escalation Study to Characterize the Safety, Tolerability, Pharmacokinetics, and Maximum Tolerated Dose of BAY1143572 Given in a Once-daily or an Intermittent Dosing Schedule in Subjects With Advanced Malignancies

The purpose of this study Part A is to determine the safety, tolerability and the pharmacokinetics of BAY1143572 in subjects with advanced malignancies, which are either refractory to or ineligible for treatment with standard agents.

The purpose of this study Part B is:

Determine the safety, tolerability, pharmacokinetics (PK) and maximum tolerated dose (MTDG-CSF) of BAY1143572 with concurrent administration of the granulocyte colony-stimulating factors (G-CSF) in an intermittent and continuous dosing schedule in subjects with advanced malignancies.

Study Overview

• Status: Completed
• Conditions: Neoplasms
• Intervention / Treatment: Drug: BAY1143572

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 110-744
  • Seoul, Korea, Republic of, 120-752
  • Seoul, Korea, Republic of, 05505
• Singapore
  • Singapore, Singapore, 119228
  • Singapore, Singapore, 169610
• Taiwan
  • Taipei, Taiwan, 10002
• United States
  • Arkansas
    • Fayetteville, Arkansas, United States, 72703
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
  • New York
    • New York, New York, United States, 10032
  • South Carolina
    • Charleston, South Carolina, United States, 29425

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:

• Male or female subjects aged >/=21 years
• Dose escalation phase: Subjects with histologically or cytologically confirmed advanced malignancies (solid tumors and malignant lymphomas) who were refractory to or had exhausted all available therapies. Subjects had to have evaluable or measurable disease (as per RECIST 1.1 or Cheson 2007 criteria).
• Expansion phase only: Subjects with advanced, histologically or cytologically confirmed gastric cancer, triple negative breast cancer (TNBC), or diffuse large B-cell lymphoma (DLBCL), who were refractory to or had exhausted all available therapies. Subjects had to have evaluable or measurable disease (as per RECIST 1.1 or Cheson 2007 criteria).
• Archival tumor tissue to conduct molecular and / or genetic studies must be collected from all study subjects enrolled in this study.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
• Life expectancy of at least 12 weeks
• Adequate bone marrow, liver, and renal functions as assessed by laboratory analysis to be conducted within 7 days prior to the first dose of study drug
• International normalized ratio (INR) and partial thromboplastin time (PTT) </=1.5 times ULN (upper limit of normal)

Exclusion Criteria:

• Known hypersensitivity to the study drug or excipients of the preparation or any agent given in association with this study
• History of cardiac disease including congestive heart failure > New York Heart Association (NYHA) Class II, unstable angina (anginal symptoms at rest) or new-onset angina (within the last 6 months) or myocardial infarction within the past 6 months and cardiac arrhythmias requiring anti-arrhythmic therapy except for beta-blockers and digoxin; evidence for uncontrolled coronary artery disease (e.g. angina pectoris, myocardial infarction within 6 months prior to study entry, major regional wall motion abnormalities upon baseline echocardiography)
• Previous pulmonary embolism within 12 months prior to study entry
• Uncontrolled hypertension defined as systolic blood pressure >150 mmHg or diastolic blood pressure >90 mmHg on 2 or more consecutive blood pressure readings, despite optimal medical management
• Moderate or severe hepatic impairment, i.e. Child-Pugh class B or C
• Known history of human immunodeficiency virus (HIV) infection
• Chronic or active hepatitis B or C, requiring antiviral therapy
• Active clinically serious infections of > Grade 2 and/or active infections that require treatment with systemic agent
• Uncontrolled seizure disorder requiring therapy (such as steroids or anti-epileptics with significant CYP interaction)
• Evidence or history of bleeding disorder, i.e. any hemorrhage / bleeding event of > Grade 2 within 4 weeks prior to the first dose of study drug

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BAY1143572 [continuous]; BAY1143572 will be administered from cycle 1, day 1 (C1D1) onwards once daily continuously	Drug: BAY1143572
Experimental: BAY1143572 [on/off]; BAY1143572 will be administered from C1D1 in a 3 days on/4 days off schedule	Drug: BAY1143572

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with adverse events as a measure of safety and tolerability		Up to 2 years
Maximum tolerated dose (MTD) of BAY1143572	In Part A: Maximum tolerated dose (MTD) of BAY1143572 In Part B; Maximum tolerated dose ( MTD) with G-CSF of BAY114357 The MTD is defined as the highest dose that can be given such that not more than 20% of subjects experience a dose limiting toxicity (DLT) during cycle 1.	Up to 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum total drug concentration (Cmax)		Cycle 1, Day 1 and Day 15 (each cycle is 28 days)
Area under the plasma concentration-time curve from time zero to 24 hours (AUC(0-24)		Cycle 1, Day 1 and Day 15 (each cycle is 28 days)
Area under the plasma concentration-time curve from time zero to infinity (AUC)		Cycle 1, Day 1 and Day 15 (each cycle is 28 days)
Time of maximum observed concentration (tmax)		Cycle 1, Day 1 and Day 15 (each cycle is 28 days)
Tumor response based on RECIST 1.1 or Cheson 2007 criteria		Up to 100 weeks
Biomarker evaluation by determination of MYC protein expression and PCNA mRNA	PCNA: proliferating cell nuclear Antigen mRNA: messenger ribonucleic acid	Cycle 1, Day 1, Day 8 and Day 15 (each cycle is 28 days)

Collaborators and Investigators

• Sponsor: Bayer

Study record dates

Study Major Dates

• Study Start (Actual): September 26, 2013
• Primary Completion (Actual): August 17, 2016
• Study Completion (Actual): September 19, 2016

Study Registration Dates

• First Submitted: September 5, 2013
• First Submitted That Met QC Criteria: September 5, 2013
• First Posted (Estimate): September 10, 2013

Study Record Updates

• Last Update Posted (Actual): October 20, 2017
• Last Update Submitted That Met QC Criteria: October 19, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: DLBCL; Gastric cancer; TNBC; Advanced malignancies
• Other Study ID Numbers: 16519