Clinical trial NCT02047890: Japanese BAY1000394 Monotherapy Phase I Study
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neoplasms
Keywords: CDK inhibitor
BAY1000394
Advanced malignancies
Japanese
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2014-01-28
Enrollment: 12
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of participants with adverse events as a measure of safety and tolerability
timeFrame: 6 months
measure: Number of participants with abnormal lab parameters based on descriptive statistics
timeFrame: 6 months
measure: Maximum observed drug concentration (Cmax) for BAY1000394 and its metabolite M-1
timeFrame: 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)
measure: Cmax divided by dose per body weight (Cmax,norm) for BAY1000394 and its metabolite M-1
timeFrame: 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)
measure: Cmax divided by dose (Cmax/D) for BAY1000394 and its metabolite M-1
timeFrame: 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)
measure: Area under the concentration versus time curve from zero to infinity after single dose (AUC) for BAY1000394 and its metabolite M-1
timeFrame: = Cycle 1 / Day 1: 0 (pre dose), 0.5, 1, 2, 4, 6, 8, 12 and 24 hours (Day 2, before morning dose)
measure: AUC from time 0 to 12 hours after single dose (AUC(0-12) for BAY1000394 and its metabolite M-1
timeFrame: Cycle 1 / Day 1: 0 (pre dose), 0.5, 1, 2, 4, 6, 8 and 12 hours
measure: AUC divided by dose per body weight (AUCnorm) for BAY1000394 and its metabolite M-1
timeFrame: Cycle 1 / Day 1: 0 (pre dose), 0.5, 1, 2, 4, 6, 8, 12 and 24 hours (Day 2, before morning dose)
measure: AUCnorm from time 0 to 12 hours after single dose (AUC(0-12),norm) for BAY1000394 and its metabolite M-1
timeFrame: Cycle 1 / Day 1: 0 (pre dose), 0.5, 1, 2, 4, 6, 8 and 12 hours
measure: AUC divided by dose (AUC/D) for BAY1000394 and its metabolite M-1
timeFrame: Cycle 1 / Day 1: 0 (pre dose), 0.5, 1, 2, 4, 6, 8, 12 and 24 hours (Day 2, before morning dose)
measure: Time to reach Cmax (tmax) for BAY1000394 and its metabolite M-1
timeFrame: 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)
measure: Terminal half-life (t½) for BAY1000394 and its metabolite M-1
timeFrame: 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)
measure: Maximum observed drug concentration after multiple dosing (Cmax,md) for BAY1000394 and its metabolite M-1
timeFrame: Cycle 1 / Day 10 : 0 (before morning dose), 0.5, 1, 2, 4, 6, 8 and 12 hours (before evening dose)
measure: Cmax divided by dose per body weight after multiple dosing (Cmax,norm,md) for BAY1000394 and its metabolite M-1
timeFrame: Cycle 1 / Day 10 : 0 (before morning dose), 0.5, 1, 2, 4, 6, 8 and 12 hours (before evening dose)
measure: Cmax divided by dose (Cmax,md/D) for BAY1000394 and its metabolite M-1
timeFrame: Cycle 1 / Day 10 : 0 (before morning dose), 0.5, 1, 2, 4, 6, 8 and 12 hours (before evening dose)
measure: AUC from time 0 to 12 hours after multiple dosing (AUC(0-12),md) for BAY1000394 and its metabolite M-1
timeFrame: Cycle 1 / Day 10 : 0 (before morning dose), 0.5, 1, 2, 4, 6, 8 and 12 hours (before evening dose)
measure: AUCnorm from time 0 to 12 hours after multiple dosing (AUC(0-12),norm,md) for BAY1000394 and its metabolite M-1
timeFrame: Cycle 1 / Day 10 : 0 (before morning dose), 0.5, 1, 2, 4, 6, 8 and 12 hours (before evening dose)
measure: AUC from time 0 to 12 hours divided by dose after multiple dosing for BAY1000394 and its metabolite M-1
timeFrame: Cycle 1 / Day 10 : 0 (before morning dose), 0.5, 1, 2, 4, 6, 8 and 12 hours (before evening dose)
Secondary outcomes:
measure: Tumor response
timeFrame: Screening and on Day 21 of even numbered cycle
Other outcomes:
Locations:
city: Kashiwa
country: Japan
state: Chiba
city: Fukuoka
country: Japan
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References: