Clinical trial NCT01404390: Japanese BAY80-6946 Monotherapy Phase I Study
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neoplasms
Keywords: Phase I
Japanese
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2011-07-28
Enrollment: 10
Sex: ALL
Minimum age (years): 20
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of subjects with adverse events
timeFrame: 169 days
measure: Maximum drug concentration in plasma after single dose administration (Cmax)
timeFrame: 0 - 168 hours in Cycle1 Day1, 0 - 25 hours in Cycle1 Day15, 0 - 8 hours in Cycle3 Day15
measure: Cmax divided by dose (mg) per kg body weight (Cmax,norm)
timeFrame: 0 - 168 hours in Cycle1 Day1, 0 - 25 hours in Cycle1 Day15, 0 - 8 hours in Cycle3 Day15
measure: Cmax divided by dose (mg) (Cmax/D)
timeFrame: 0 - 168 hours in Cycle1 Day1, 0 - 25 hours in Cycle1 Day15, 0 - 8 hours in Cycle3 Day15
measure: Area under the concentration-time curve time 0 to 8 hours (AUC(0-8))
timeFrame: 0 - 168 hours in Cycle1 Day1, 0 - 25 hours in Cycle1 Day15, 0 - 8 hours in Cycle3 Day15
measure: Area under the concentration-time curve from time 0 to 25 hours (AUC(0-25))
timeFrame: 0 - 168 hours in Cycle1 Day1, 0 - 25 hours in Cycle1 Day15
measure: AUC(0-25) divided by dose (mg) per kg body weight (AUC(0-25)norm)
timeFrame: 0 - 168 hours in Cycle1 Day1, 0 - 25 hours in Cycle1 Day15
measure: AUC(0-25) divided by dose (mg) (AUC(0-25)/D)
timeFrame: 0 - 168 hours in Cycle1 Day1, 0 - 25 hours in Cycle1 Day15
measure: AUC from time 0 to last data point (AUC(0-tlast))
timeFrame: 0 - 168 hours in Cycle1 Day1, 0 - 25 hours in Cycle1 Day15
measure: Time to maximum drug concentration in plasma (tmax)
timeFrame: 0 - 168 hours in Cycle1 Day1, 0 - 25 hours in Cycle1 Day15, 0 - 8 hours in Cycle3 Day 15
Secondary outcomes:
measure: Area under the plasma concentration-time curve of (AUC) of BAY80-6946
timeFrame: 0 - 168 hours in Cycle1 Day1
measure: Half-life associated with terminal slope of drug in plasma (t1/2)
timeFrame: 0 - 168 hours in Cycle1 Day1
measure: Mean residence time of drug in plasma (MRT)
timeFrame: 0 - 168 hours in Cycle1 Day1
measure: Total body clearance of drug from plasma (CL)
timeFrame: 0 - 168 hours in Cycle1 Day1
measure: Volume of drug distribution during terminal phase after single dose administration (Vz)
timeFrame: 0 - 168 hours in Cycle1 Day1
measure: Volume of drug distribution during steady state after single dose administration (Vss)
timeFrame: 0 - 168 hours in Cycle1 Day1
measure: Accumulation ratio calculated from AUC(0-8) after multiple dosing and AUC(0-8) after single dosing (RAAUC(0-8))
timeFrame: 0 - 8 hours in Cycle3 Day15
measure: Accumulation ratio calculated from AUC(0-25) after multiple dosing and AUC(0-25) after single dosing (RAAUC(0-25))
timeFrame: 0 - 25 hours in Cycle1 Day15
measure: Accumulation ration calculated from Cmax after multiple dosing and Cmax after single dosing (RACmax)
timeFrame: 0 - 168 hours in Cycle1 Day1, 0 - 25 hours in Cycle1 Day15
measure: Overall tumor response rate
timeFrame: 176 days
measure: Overall disease control rate
timeFrame: 176 days
measure: Time to progression of cancer growth
timeFrame: 176 days
measure: Progression-free survival time
timeFrame: 176 days
Other outcomes:
Locations:
city: Kashiwa
country: Japan
state: Chiba
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References:
citation: 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.