The purpose of this study is to determine whether recombinant human arginase (PEG-BCT-100) is safe and effective in the treatment of advanced hepatocellular carcinoma (HCC).
The primary objectives of this study are: * To establish a safe dose level for weekly intravenous administration of PEG- BCT-100 (rhArgIpeg5000) based on clinical and laboratory safety assessments following a range of doses (from 500 to \>5000 U/kg). * To define the optimal biological dose (OBD) of PEG-BCT-100 based on the pharmacodynamics (PD) of arginine depletion (ADD) relative to plasma PK of PEG- BCT-100. * To evaluate any objective tumor responses to PEG-BCT-100 in HCC patients receiving weekly doses of PEG-BCT-100 alone and in combination with standard doses of doxorubicin Secondary objectives of this study are: * To define any toxicities associated with the metabolic and cellular alterations of ADD relative to dose and PK of PEG-BCT-100 (rhArgIpeg5000). * To develop a safe and biologically active dose and schedule for PEG-BCT-100 treatment in phase 2 trials, either as monotherapy or in combination with best standard of care chemotherapy. * To confirm the safety and initial anti-tumor activity of the preferred dose and regimen of PEG-BCT-100 in 18 additional patients with advanced HCC
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
15
Week 1 (Single Dose); Weeks 3 - 11 (Weekly Dose x 8 weeks)in 8 escalation doses
Weeks 13-24 (once every 3 weeks)
Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The University of Hong Kong
Hong Kong, Hong Kong
Plasma arginase and arginine levels,as well as tumour response, i.e. an effect on growth in the milieu of arginine depletion.
Time frame: 24 weeks
Overall Survival, Time to Progression
Time frame: 24 weeks
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