check_circleStudy Completed

Neoplasms

Japanese BAY80-6946 monotherapy Phase I study

Trial purpose

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.

Key Participants Requirements

Sex

Both

Age

20 - 80 Years
  • - 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

  • - 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

Trial summary

Enrollment Goal
10
Trial Dates
August 2011 - July 2012
Phase
Phase 1
Could I Receive a placebo
No
Products
Aliqopa (Copanlisib, BAY80-6946)
Accepts Healthy Volunteer
No

Where to participate

StatusInstitutionLocation
Completed
Kashiwa, 277-8577, Japan

Primary Outcome

  • Number of subjects with adverse events
    date_rangeTime Frame:
    169 days
    enhanced_encryption
    Safety Issue:
    Yes
  • Maximum drug concentration in plasma after single dose administration (Cmax)
    date_rangeTime Frame:
    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)
    date_rangeTime Frame:
    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)
    date_rangeTime Frame:
    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))
    date_rangeTime Frame:
    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))
    date_rangeTime Frame:
    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)
    date_rangeTime Frame:
    0 - 168 hours in Cycle1 Day1, 0 - 25 hours in Cycle1 Day15
  • AUC(0-25) divided by dose (mg) (AUC(0-25)/D)
    date_rangeTime Frame:
    0 - 168 hours in Cycle1 Day1, 0 - 25 hours in Cycle1 Day15
  • AUC from time 0 to last data point (AUC(0-tlast))
    date_rangeTime Frame:
    0 - 168 hours in Cycle1 Day1, 0 - 25 hours in Cycle1 Day15
  • Time to maximum drug concentration in plasma (tmax)
    date_rangeTime Frame:
    0 - 168 hours in Cycle1 Day1, 0 - 25 hours in Cycle1 Day15, 0 - 8 hours in Cycle3 Day 15

Secondary Outcome

  • Area under the plasma concentration-time curve of (AUC) of BAY80-6946
    date_rangeTime Frame:
    0 - 168 hours in Cycle1 Day1
    enhanced_encryption
    Safety Issue:
    No
  • Half-life associated with terminal slope of drug in plasma (t1/2)
    date_rangeTime Frame:
    0 - 168 hours in Cycle1 Day1
  • Mean residence time of drug in plasma (MRT)
    date_rangeTime Frame:
    0 - 168 hours in Cycle1 Day1
  • Total body clearance of drug from plasma (CL)
    date_rangeTime Frame:
    0 - 168 hours in Cycle1 Day1
  • Volume of drug distribution during terminal phase after single dose administration (Vz)
    date_rangeTime Frame:
    0 - 168 hours in Cycle1 Day1
  • Volume of drug distribution during steady state after single dose administration (Vss)
    date_rangeTime Frame:
    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))
    date_rangeTime Frame:
    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))
    date_rangeTime Frame:
    0 - 25 hours in Cycle1 Day15
  • Accumulation ration calculated from Cmax after multiple dosing and Cmax after single dosing (RACmax)
    date_rangeTime Frame:
    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
    date_rangeTime Frame:
    176 days
  • Overall disease control rate
    Proportion of subjects who had a best response rating of complete response, partial response or stable disease
    date_rangeTime Frame:
    176 days
  • Time to progression of cancer growth
    date_rangeTime Frame:
    176 days
  • Progression-free survival time
    date_rangeTime Frame:
    176 days

Trial design

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
Trial Type
Interventional
Intervention Type
Drug
Trial Purpose
Treatment
Allocation
Non-randomized
Blinding
Open Label
Assignment
Factorial Assignment
Trial Arms
2