Japanese BAY1000394 Monotherapy Phase I Study

Study Overview
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Brief Summary
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This is an open-label, non-randomized, dose-escalating Phase I study to evaluate the safety, tolerability, pharmacokinetics of BAY1000394 given in a 3 days on / 4 days off schedule in Japanese subjects with advanced malignancies.

Official Title
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An Open-label, Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics of BAY1000394 Given in a 3 Days on / 4 Days Off Schedule in Japanese Subjects With Advanced Malignancies

Conditions
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Neoplasms

Intervention / Treatment
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* Drug: BAY1000394 (2.5mg)
* Drug: BAY1000394 (5mg)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Japanese male or female subjects aged ≥20 years Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1 Life expectancy of at least 12 weeks Subjects with advanced, histologically or cytologically confirmed solid tumors, not amenable to any standard therapy, have no standard therapy available, or subjects must have actively refused any treatment which would be regarded standard, and if in the judgment of the investigator, experimental treatment is clinically and ethically acceptable At least 1 tumor lesion evaluable by computer tomography (CT) or scan or magnetic resonance imaging (MRI) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 Adequate bone marrow, liver, and renal functions Exclusion Criteria: Anticancer chemotherapy or immunotherapy within 4 weeks of study entry. Mitomycin C or nitrosoureas should not be given within 6 weeks of study entry. Radiotherapy to target lesions within 3 weeks prior to the first dose of study drug. Use of biological response modifiers, such as granulocyte colony-stimulating factor (G-CSF), within 3 weeks prior to the first dose of study drug. Symptomatic metastatic brain or meningeal tumors. Investigational drug treatment outside of this study during or within 4 weeks prior to study entry. Blood pressure <100/60 mmHg or pulse >100 BPM

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BAY1000394<br>Approximately 12 subjects will be included: 3 to 6 evaluable subjects for each cohort. The cycle length will be 3 weeks (21 days). | Drug: BAY1000394 (2.5mg)<br>* BAY1000934 2.5mg twice a day (bid) in a 3 days on and 4 days off schedule. (Cohort 1)<br>Drug: BAY1000394 (5mg)<br>* BAY1000934 5mg twice a day (bid) in a 3 days on and 4 days off schedule. (Cohort 2)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events as a measure of safety and tolerability |  | 6 months | 
| Number of participants with abnormal lab parameters based on descriptive statistics |  | 6 months | 
| Maximum observed drug concentration (Cmax) for BAY1000394 and its metabolite M-1 |  | Cycle 1 / Day 1: 0 (pre dose), 0.5, 1, 2, 4, 6, 8, 12 and 24 hours (Day 2, before morning dose). Cycle 1 / Day 10 : 0 (before morning dose), 0.5, 1, 2, 4, 6, 8 and 12 hours (before evening dose) | 
| Cmax divided by dose per body weight (Cmax,norm) for BAY1000394 and its metabolite M-1 |  | Cycle 1 / Day 1: 0 (pre dose), 0.5, 1, 2, 4, 6, 8, 12 and 24 hours (Day 2, before morning dose). Cycle 1 / Day 10 : 0 (before morning dose), 0.5, 1, 2, 4, 6, 8 and 12 hours (before evening dose) | 
| Cmax divided by dose (Cmax/D) for BAY1000394 and its metabolite M-1 |  | Cycle 1 / Day 1: 0 (pre dose), 0.5, 1, 2, 4, 6, 8, 12 and 24 hours (Day 2, before morning dose). Cycle 1 / Day 10 : 0 (before morning dose), 0.5, 1, 2, 4, 6, 8 and 12 hours (before evening dose) | 
| Area under the concentration versus time curve from zero to infinity after single dose (AUC) for BAY1000394 and its metabolite M-1 |  | = Cycle 1 / Day 1: 0 (pre dose), 0.5, 1, 2, 4, 6, 8, 12 and 24 hours (Day 2, before morning dose) | 
| AUC from time 0 to 12 hours after single dose (AUC(0-12) for BAY1000394 and its metabolite M-1 |  | Cycle 1 / Day 1: 0 (pre dose), 0.5, 1, 2, 4, 6, 8 and 12 hours | 
| AUC divided by dose per body weight (AUCnorm) for BAY1000394 and its metabolite M-1 |  | Cycle 1 / Day 1: 0 (pre dose), 0.5, 1, 2, 4, 6, 8, 12 and 24 hours (Day 2, before morning dose) | 
| AUCnorm from time 0 to 12 hours after single dose (AUC(0-12),norm) for BAY1000394 and its metabolite M-1 |  | Cycle 1 / Day 1: 0 (pre dose), 0.5, 1, 2, 4, 6, 8 and 12 hours | 
| AUC divided by dose (AUC/D) for BAY1000394 and its metabolite M-1 |  | Cycle 1 / Day 1: 0 (pre dose), 0.5, 1, 2, 4, 6, 8, 12 and 24 hours (Day 2, before morning dose) | 
| Time to reach Cmax (tmax) for BAY1000394 and its metabolite M-1 |  | Cycle 1 / Day 1: 0 (pre dose), 0.5, 1, 2, 4, 6, 8, 12 and 24 hours (Day 2, before morning dose). Cycle 1 / Day 10 : 0 (before morning dose), 0.5, 1, 2, 4, 6, 8 and 12 hours (before evening dose) | 
| Terminal half-life (t½) for BAY1000394 and its metabolite M-1 |  | Cycle 1 / Day 1: 0 (pre dose), 0.5, 1, 2, 4, 6, 8, 12 and 24 hours (Day 2, before morning dose). Cycle 1 / Day 10 : 0 (before morning dose), 0.5, 1, 2, 4, 6, 8 and 12 hours (before evening dose) | 
| Maximum observed drug concentration after multiple dosing (Cmax,md) for BAY1000394 and its metabolite M-1 |  | Cycle 1 / Day 10 : 0 (before morning dose), 0.5, 1, 2, 4, 6, 8 and 12 hours (before evening dose) | 
| Cmax divided by dose per body weight after multiple dosing (Cmax,norm,md) for BAY1000394 and its metabolite M-1 |  | Cycle 1 / Day 10 : 0 (before morning dose), 0.5, 1, 2, 4, 6, 8 and 12 hours (before evening dose) | 
| Cmax divided by dose (Cmax,md/D) for BAY1000394 and its metabolite M-1 |  | Cycle 1 / Day 10 : 0 (before morning dose), 0.5, 1, 2, 4, 6, 8 and 12 hours (before evening dose) | 
| AUC from time 0 to 12 hours after multiple dosing (AUC(0-12),md) for BAY1000394 and its metabolite M-1 |  | Cycle 1 / Day 10 : 0 (before morning dose), 0.5, 1, 2, 4, 6, 8 and 12 hours (before evening dose) | 
| AUCnorm from time 0 to 12 hours after multiple dosing (AUC(0-12),norm,md) for BAY1000394 and its metabolite M-1 |  | Cycle 1 / Day 10 : 0 (before morning dose), 0.5, 1, 2, 4, 6, 8 and 12 hours (before evening dose) | 
| AUC from time 0 to 12 hours divided by dose after multiple dosing for BAY1000394 and its metabolite M-1 |  | Cycle 1 / Day 10 : 0 (before morning dose), 0.5, 1, 2, 4, 6, 8 and 12 hours (before evening dose) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor response |  | Screening and on Day 21 of even numbered cycle | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CDK inhibitor, BAY1000394, Advanced malignancies, Japanese