Japanese BAY80-6946 Monotherapy Phase I Study

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

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.

Study Overview

• Status: Completed
• Conditions: Neoplasms
• Intervention / Treatment: Drug: BAY80-6946; Drug: BAY80-6946

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Chiba
    • Kashiwa, Chiba, Japan, 277-8577

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Factorial Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome 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 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

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

General Publications

• Doi T, Fuse N, Yoshino T, Kojima T, Bando H, Miyamoto H, Kaneko M, Osada M, Ohtsu A. A Phase I study of intravenous PI3K inhibitor copanlisib in Japanese patients with advanced or refractory solid tumors. Cancer Chemother Pharmacol. 2017 Jan;79(1):89-98. doi: 10.1007/s00280-016-3198-0. Epub 2016 Dec 3.

Study record dates

Study Major Dates

• Study Start (Actual): August 18, 2011
• Primary Completion (Actual): March 22, 2012
• Study Completion (Actual): July 12, 2012

Study Registration Dates

• First Submitted: July 27, 2011
• First Submitted That Met QC Criteria: July 27, 2011
• First Posted (Estimate): July 28, 2011

Study Record Updates

• Last Update Posted (Actual): December 14, 2017
• Last Update Submitted That Met QC Criteria: December 13, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Keywords: Japanese; Phase I
• Other Study ID Numbers: 15205