Description:
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.
Title
- Brief Title: Open Label Phase I Dose Escalation Study With BAY1143572 in Patients With Advanced Cancer
- Official Title: 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
Clinical Trial IDs
- ORG STUDY ID:
16519
- NCT ID:
NCT01938638
Conditions
Interventions
Drug | Synonyms | Arms |
---|
BAY1143572 | | BAY1143572 [continuous] |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
BAY1143572 [continuous] | Experimental | BAY1143572 will be administered from cycle 1, day 1 (C1D1) onwards once daily continuously | |
BAY1143572 [on/off] | Experimental | BAY1143572 will be administered from C1D1 in a 3 days on/4 days off schedule | |
Eligibility Criteria
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
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 21 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Number of participants with adverse events as a measure of safety and tolerability |
Time Frame: | Up to 2 years |
Safety Issue: | |
Description: | 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. |
Secondary Outcome Measures
Measure: | Maximum total drug concentration (Cmax) |
Time Frame: | Cycle 1, Day 1 and Day 15 (each cycle is 28 days) |
Safety Issue: | |
Description: | |
Measure: | Area under the plasma concentration-time curve from time zero to 24 hours (AUC(0-24) |
Time Frame: | Cycle 1, Day 1 and Day 15 (each cycle is 28 days) |
Safety Issue: | |
Description: | |
Measure: | Area under the plasma concentration-time curve from time zero to infinity (AUC) |
Time Frame: | Cycle 1, Day 1 and Day 15 (each cycle is 28 days) |
Safety Issue: | |
Description: | |
Measure: | Time of maximum observed concentration (tmax) |
Time Frame: | Cycle 1, Day 1 and Day 15 (each cycle is 28 days) |
Safety Issue: | |
Description: | |
Measure: | Tumor response based on RECIST 1.1 or Cheson 2007 criteria |
Time Frame: | Up to 100 weeks |
Safety Issue: | |
Description: | |
Measure: | Biomarker evaluation by determination of MYC protein expression and PCNA mRNA |
Time Frame: | Cycle 1, Day 1, Day 8 and Day 15 (each cycle is 28 days) |
Safety Issue: | |
Description: | PCNA: proliferating cell nuclear Antigen mRNA: messenger ribonucleic acid |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Completed |
Lead Sponsor: | Bayer |
Trial Keywords
- Advanced malignancies
- TNBC
- DLBCL
- Gastric cancer
Last Updated
October 20, 2017