Japanese BAY1000394 Monotherapy Phase I Study

Phase 1

Completed

• Conditions: Neoplasms
• Interventions: Drug: BAY1000394 (2.5mg); Drug: BAY1000394 (5mg)

• Registration Number: NCT02047890
• Lead Sponsor: Bayer

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2014-01-27
• Study First Submitted QC: 2014-01-27
• Study First Posted: 2014-01-28
• Study Start: 2014-05-19
• Primary Completion: 2015-01-06
• Study Completion: 2018-07-19
• Status Verified: 2019-06
• Last Update Submitted: 2019-06-20
• Last Update Posted: 2019-06-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 12

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
BAY1000394	BAY1000394 (2.5mg)	Approximately 12 subjects will be included: 3 to 6 evaluable subjects for each cohort. The cycle length will be 3 weeks (21 days).
BAY1000394	BAY1000394 (5mg)	Approximately 12 subjects will be included: 3 to 6 evaluable subjects for each cohort. The cycle length will be 3 weeks (21 days).

Primary Outcome Measures

Name	Time	Method
Number of participants with abnormal lab parameters based on descriptive statistics	6 months
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)
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)
Number of participants with adverse events as a measure of safety and tolerability	6 months
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)
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

Name	Time	Method
Tumor response	Screening and on Day 21 of even numbered cycle