BAY86-9766 Plus Gemcitabine Phase I Study in Asian

Study Overview
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Brief Summary
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This is an open-label, uncontrolled, Phase Ib study designed to evaluate the safety, tolerability, and pharmacokinetics of BAY86-9766 when given as a single agent and in combination with gemcitabine in Asian patients with advanced or refractory solid tumors.Blood samples for PK (pharmacokinetics) analyses will be collected after a single dose of BAY86-9766, multiple doses of BAY86-9766, and combination treatment of gemcitabine and BAY86-9766. Safety evaluation will include adverse events assessment, vital signs, laboratory tests, 12-lead ECG ECG (electrocardiography), cardiac function test, and ophthalmologic examination at various time points during the study.

Official Title
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A Multi-center, Phase Ib Study of MEK (Mitogen Activated Protein Kinase/ERK Kinase) Inhibitor BAY86-9766 Plus Gemcitabine in Asian Patients With Advanced or Refractory Solid Tumors

Conditions
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Neoplasms

Intervention / Treatment
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* Drug: Refametinib (BAY86-9766)
* Drug: Gemcitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients >/= 18 years of age, with histologically or cytologically documented advanced or refractory solid tumors not amenable to standard therapy Patients must have at least one measurable or evaluable tumor lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 Patients must have a life expectancy of at least 12 weeks, and an Eastern Cooperative Oncology Group Performance Status (ECOG PS) </=1. Exclusion Criteria: History of cardiac disease Active clinically serious infections > Common Terminology Criteria for Adverse Events (CTCAE) grade 2 Known human immunodeficiency virus (HIV) infection Uncontrolled seizure disorder Undergoing renal dialysis Known bleeding diathesis History of organ allograft Pregnant or breast feeding women

Ages Eligible for Study
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Minimum Age: 18 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: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Refametinib (BAY86-9766)+ Gemcitabine<br>Single dose of BAY86-9766 on Cycle 1 Day -17; twice daily dosing every day starting on day -14, start dose 50mg bid ( 30mg or 20mg are possible based on adverse events need) in addition with Gemcitabine intravenous on day 1,8 and 15 1000mg/m2 | Drug: Refametinib (BAY86-9766)<br> <br> Drug: Gemcitabine<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma concentration of BAY86-9766 |  | Multiple time points up to 6 day | 
| Plasma concentration of M17 and M11 |  | Multiple time points up to 6 day | 
| Plasma concentration of Gemcitabine |  | Multiple time points up to 6 day | 
| Plasma concentration of dFdU |  | Multiple time points up to 6 day | 
| Number of adverse events, or abnormal parameters as a measure of safety and tolerability | Parameters are laboratory parameters, vital signs, ECG parameters, cardiac function, and parameters of ophthalmologic examinations | Up to 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of BAY86-9766 shown by a discrete scale | Elements of the scale are :Complete Response (CR), Partial Response (PR), Stable Disease (SD) or Progressive Disease (PD) | Up to 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase I, Pharmacokinetics, Safety measurements