Study Completed

Neoplasms

Bayer Identifier:

16519

ClinicalTrials.gov Identifier:

NCT01938638

EudraCT Number:

Not Available

EU CT Number:

Not Available

Open label Phase I dose escalation study with BAY1143572 in patients with advanced cancer

Trial 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.

Key Participants Requirements

Sex

Both

Age

21 - N/A

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)
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

Trial summary

Enrollment Goal

Trial Dates

September 2013 - September 2016

Phase

Phase 1

Could I Receive a placebo

Products

Atuveciclib (BAY1143572)

Accepts Healthy Volunteer

Where to participate

Status	Institution	Location
Completed		Seoul, 110-744, Korea, Republic Of
Completed		Singapore, 119228, Singapore
Completed		Singapore, 169610, Singapore
Completed		Seoul, 120-752, Korea, Republic Of
Completed		New York, 10032, United States
Terminated		Boston, 02215, United States
Terminated		Taipei, 10002, Taiwan
Completed		Seoul, 05505, Korea, Republic Of
Completed		Hackensack, 07601, United States
Terminated		Charleston, 29425, United States
Completed		Ann Arbor, 48109, United States
Completed		Fayetteville, 72703, United States
Terminated		Boston, 02215, United States

Primary Outcome

Number of participants with adverse events as a measure of safety and tolerability
Time Frame:
Up to 2 years
Safety Issue:
Yes
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.
Time Frame:
Up to 1 year
Safety Issue:
Yes

Secondary Outcome

Maximum total drug concentration (Cmax)
Time Frame:
Cycle 1, Day 1 and Day 15 (each cycle is 28 days)
Safety Issue:
No
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)
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)
Time of maximum observed concentration (tmax)
Time Frame:
Cycle 1, Day 1 and Day 15 (each cycle is 28 days)
Tumor response based on RECIST 1.1 or Cheson 2007 criteria
Time Frame:
Up to 100 weeks
Biomarker evaluation by determination of MYC protein expression and PCNA mRNA
PCNA: proliferating cell nuclear Antigen mRNA: messenger ribonucleic acid
Time Frame:
Cycle 1, Day 1, Day 8 and Day 15 (each cycle is 28 days)

Trial design

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

Trial Type

Interventional

Intervention Type

Drug

Trial Purpose

Treatment

Allocation

Non-randomized

Blinding

Open Label

Assignment

Parallel Assignment

Trial Arms

Additional Information

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