Neoplasms
Conditions
Keywords
Phase I, Japanese
Brief summary
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.
Interventions
DRUGBAY80-6946
0.4mg/ kg, iv, day 1,8 and 15, every 28 days
Sponsors
Bayer
Study design
Allocation
NON_RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | 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
| Measure | Time frame | Description |
|---|---|---|
| Overall disease control rate | 176 days | Proportion of subjects who had a best response rating of complete response, partial response or stable disease |
| Area under the plasma concentration-time curve of (AUC) of BAY80-6946 | 0 - 168 hours in Cycle1 Day1 | — |
| Progression-free survival time | 176 days | — |
| Time to progression of cancer growth | 176 days | — |
| 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 | 176 days | Proportion of subjects with confirmed complete and partial response |
Countries
Japan
Outcome results
None listed