Japanese BAY80-6946 Monotherapy Phase I Study

Study Overview
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Brief Summary
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This study will be conducted as an open label, single centre, Phase I study of PI3K (phosphatidyl inositol 3 kinase) inhibitor BAY80-6946 in Japanese patients with advanced or refractory solid tumours. The eligible subjects will be dosed intravenously at Day 1, Day 8 and Day 15 with three weeks on and one week off in each treatment cycle.

Official Title
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An Open Label, Single Centre, Phase I Study of PI3K Inhibitor BAY80-6946 to Evaluate the Safety, Tolerability and Pharmacokinetics in Japanese Patients With Advanced or Refractory Solid Tumours

Conditions
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Neoplasms

Intervention / Treatment
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* Drug: BAY80-6946
* Drug: BAY80-6946


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cancer patients Japanese patients, who are at least 20 years of age Histological or cytological documentation of non-hematologic, malignant solid tumours, excluding primary brain or spinal tumours, with no past or current involvement in the central nervous system (CNS) At least one measurable lesion or evaluable disease according to RECIST (version 1.1) Eastern Cooperative Oncology performance status (ECOG-PS) of 0 or 1 Life expectancy of at least 12 weeks Advanced or refractory solid tumours not amenable to standard therapy, at the first screening examination/visit Exclusion Criteria: Anticancer chemotherapy or immunotherapy during the study or within 4 weeks of first study treatment. Patients must have recovered from the toxic effects of the previous anti-cancer chemotherapy or immunotherapy by the investigator (with the exception of alopecia). Radiotherapy to target lesions during study or within 4 weeks of first study treatment Investigational drug therapy outside of this trial during or within 4 weeks of first study treatment Current diagnosis of Type I or II diabetes mellitus or fasting blood glucose level >125 mg/dL at screening, and/or HbA1c>/= 6.5% Past and current histories of cardiac disease congestive heart failure > New York Heart Association (NYHA) Class II; active coronary artery disease, myocardial infarction within 6 months prior to study entry; new onset of angina within 3 months prior to study entry or unstable angina or ventricular cardiac arrhythmias requiring anti-arrhythmic therapy Active and clinically serious infections >Grade 2 (National Cancer Institute Common Terminology Criteria for Adverse Events [NCI-CTCAE] version 4.03) Uncontrolled hypertension defined as systolic blood pressure >150 mm Hg or diastolic pressure > 90 mm Hg, despite optimal medical management Patients undergoing renal dialysis Pregnant or breast feeding women

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 80 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
Allocation: Non-Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br> | Drug: BAY80-6946<br>* 0.4mg/ kg, iv, day 1,8 and 15, every 28 days<br>|
| Experimental: Arm 2<br> | Drug: BAY80-6946<br>* 0.8mg/ kg, iv, day 1,8 and 15, every 28 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with adverse events |  | 169 days | 
| Maximum drug concentration in plasma after single dose administration (Cmax) |  | 0 - 168 hours in Cycle1 Day1, 0 - 25 hours in Cycle1 Day15, 0 - 8 hours in Cycle3 Day15 | 
| Cmax divided by dose (mg) per kg body weight (Cmax,norm) |  | 0 - 168 hours in Cycle1 Day1, 0 - 25 hours in Cycle1 Day15, 0 - 8 hours in Cycle3 Day15 | 
| Cmax divided by dose (mg) (Cmax/D) |  | 0 - 168 hours in Cycle1 Day1, 0 - 25 hours in Cycle1 Day15, 0 - 8 hours in Cycle3 Day15 | 
| Area under the concentration-time curve time 0 to 8 hours (AUC(0-8)) |  | 0 - 168 hours in Cycle1 Day1, 0 - 25 hours in Cycle1 Day15, 0 - 8 hours in Cycle3 Day15 | 
| Area under the concentration-time curve from time 0 to 25 hours (AUC(0-25)) |  | 0 - 168 hours in Cycle1 Day1, 0 - 25 hours in Cycle1 Day15 | 
| AUC(0-25) divided by dose (mg) per kg body weight (AUC(0-25)norm) |  | 0 - 168 hours in Cycle1 Day1, 0 - 25 hours in Cycle1 Day15 | 
| AUC(0-25) divided by dose (mg) (AUC(0-25)/D) |  | 0 - 168 hours in Cycle1 Day1, 0 - 25 hours in Cycle1 Day15 | 
| AUC from time 0 to last data point (AUC(0-tlast)) |  | 0 - 168 hours in Cycle1 Day1, 0 - 25 hours in Cycle1 Day15 | 
| Time to maximum drug concentration in plasma (tmax) |  | 0 - 168 hours in Cycle1 Day1, 0 - 25 hours in Cycle1 Day15, 0 - 8 hours in Cycle3 Day 15 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration-time curve of (AUC) of BAY80-6946 |  | 0 - 168 hours in Cycle1 Day1 | 
| Half-life associated with terminal slope of drug in plasma (t1/2) |  | 0 - 168 hours in Cycle1 Day1 | 
| Mean residence time of drug in plasma (MRT) |  | 0 - 168 hours in Cycle1 Day1 | 
| Total body clearance of drug from plasma (CL) |  | 0 - 168 hours in Cycle1 Day1 | 
| Volume of drug distribution during terminal phase after single dose administration (Vz) |  | 0 - 168 hours in Cycle1 Day1 | 
| Volume of drug distribution during steady state after single dose administration (Vss) |  | 0 - 168 hours in Cycle1 Day1 | 
| Accumulation ratio calculated from AUC(0-8) after multiple dosing and AUC(0-8) after single dosing (RAAUC(0-8)) |  | 0 - 8 hours in Cycle3 Day15 | 
| Accumulation ratio calculated from AUC(0-25) after multiple dosing and AUC(0-25) after single dosing (RAAUC(0-25)) |  | 0 - 25 hours in Cycle1 Day15 | 
| Accumulation ration calculated from Cmax after multiple dosing and Cmax after single dosing (RACmax) |  | 0 - 168 hours in Cycle1 Day1, 0 - 25 hours in Cycle1 Day15 | 
| Overall tumor response rate | Proportion of subjects with confirmed complete and partial response | 176 days | 
| Overall disease control rate | Proportion of subjects who had a best response rating of complete response, partial response or stable disease | 176 days | 
| Time to progression of cancer growth |  | 176 days | 
| Progression-free survival time |  | 176 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase I, Japanese