Japanese BAY80-6946 Monotherapy Phase I Study

Phase 1

Completed

• Conditions: Neoplasms
• Interventions: Drug: BAY80-6946

• Registration Number: NCT01404390
• Lead Sponsor: Bayer

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2011-07-27
• Study First Submitted QC: 2011-07-27
• Study First Posted: 2011-07-28
• Study Start: 2011-08-18
• Primary Completion: 2012-03-22
• Study Completion: 2012-07-12
• Status Verified: 2017-12
• Last Update Submitted: 2017-12-13
• Last Update Posted: 2017-12-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 10

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Arm 2	BAY80-6946	-
Arm 1	BAY80-6946	-

Primary Outcome Measures

Name	Time	Method
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
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
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
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
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
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
AUC from time 0 to last data point (AUC(0-tlast))	0 - 168 hours in Cycle1 Day1, 0 - 25 hours in Cycle1 Day15

Secondary Outcome Measures

Name	Time	Method
Total body clearance of drug from plasma (CL)	0 - 168 hours in Cycle1 Day1
Mean residence time of drug in plasma (MRT)	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
Half-life associated with terminal slope of drug in plasma (t1/2)	0 - 168 hours in Cycle1 Day1
Area under the plasma concentration-time curve of (AUC) of BAY80-6946	0 - 168 hours in Cycle1 Day1
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
Overall tumor response rate	176 days	Proportion of subjects with confirmed complete and partial response
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
Overall disease control rate	176 days	Proportion of subjects who had a best response rating of complete response, partial response or stable disease
Progression-free survival time	176 days
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
Time to progression of cancer growth	176 days