Clinical Trials /

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

NCT01938638

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.

Related Conditions:
  • Breast Carcinoma
  • Diffuse Large B-Cell Lymphoma
  • Gastric Carcinoma
Recruiting Status:

Completed

Phase:

Phase 1

Trial Eligibility

Document

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

  • Neoplasms

Interventions

DrugSynonymsArms
BAY1143572BAY1143572 [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

NameTypeDescriptionInterventions
BAY1143572 [continuous]ExperimentalBAY1143572 will be administered from cycle 1, day 1 (C1D1) onwards once daily continuously
  • BAY1143572
BAY1143572 [on/off]ExperimentalBAY1143572 will be administered from C1D1 in a 3 days on/4 days off schedule
  • BAY1143572

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 19, 2017