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 evaluate any objective tumor responses to PEG-BCT-100 in HCC patients receiving weekly doses of PEG-BCT-100 alone. * To perform PK and PD analysis * To measure Quality of Life of the patients Secondary objectives of this study are: * To define any toxicity associated with the metabolic and cellular alterations of ADD relative to dose and PK of PEG-BCT-100 (rhArgIpeg5000). * To confirm the safety and anti-tumor activity of PEG-BCT-100 at the preferred dose (1600U/kg) in 50 patients (at least 18 evaluable subjects) with advanced HCC. * To measure duration of response including Overall Survival and Time to Progression analysis
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
20
Weekly dose of PEG-BCT-100 for at least 8 weeks (or until disease progression) at 1600U/kg
Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The University of Hong Kong
Hong Kong, Hong Kong
Tumor response
Tumor response endpoints include(a)Objective response for each patient evaluated by RECIST, (b)Modified RECIST criteria will be used as secondary reference, (c) The proportion of patients achieving a partial response or complete response (d) The proportion of patients reporting disease progression by RECIST and the times to progression (e)Serial changes in plasma AFP levels after doses of PEG-BCT-100 and (f)Change in relevant viral serology from baseline to end-of-study
Time frame: 12 weeks
Overall Survival
Overall Survival measurement from the date of starting the first dose of PEG-BCT-100 until death from any cause at every 4 weeks until the patient's death, or 3 months from the last patient's study visit, through clinical visits or telephone follow-ups
Time frame: 12 weeks
Time to Progression
Time frame: 12 weeks
Plasma arginase level
The PK endpoints include (a) Dose-related peak to trough concentrations of plasma PEG-BCT-100 over time (b)Plasma clearance of PEG-BCT-100; and(c)Intra- and inter-subject variability of plasma PK parameters to assess the predictability of PEG-BCT-100 administration
Time frame: 12 weeks
Quality of Life
Measurement of Quality of Life by completing 2 questionnaires at baseline, week 8 and 4-weekly after week 8 until end of treatment visit. The Chinese version of the EORTC QLQ-C30 will be used, which contains Five functional scales and Three symptom scales. The Chinese version of EORTC QLQ-HCC18 will also be used.
Time frame: 12 weeks
Plasma arginine levels
The PD endpoints include (a)The magnitude of plasma arginine depletion relative to the dose (b)The duration of effective ADD assessed by plasma arginine \<8 µM relative to the plasma peak and time to clearance (c) The relationships of PEG-BCT-100 dose and its resultant effective ADD to changes in AFP and/or tumor symptoms and measurements(d)The temporal and quantitative relationships of depleted plasma arginine to dose and plasma concentrations of PEG-BCT-100; and (e)Correlation of prolonged arginine depletion with extended survival
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Time frame: 12 weeks