Study of Pegylated Human Recombinant Arginase for Liver Cancer (BCT-100-002)

This study has been completed.
Sponsor:
Collaborators:
The University of Hong Kong
Chinese University of Hong Kong
Information provided by (Responsible Party):
Bio-Cancer Treatment International Limited
ClinicalTrials.gov Identifier:
NCT01092091
First received: March 23, 2010
Last updated: March 13, 2012
Last verified: March 2012
  Purpose

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).


Condition Intervention Phase
Neoplasm
Hepatocellular Carcinoma
Biological: Pegylated Recombinant Human Arginase I
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Recombinant Human Arginase I (rhArgI) for Patients With Advanced Hepatocellular Carcinoma (HCC)

Resource links provided by NLM:


Further study details as provided by Bio-Cancer Treatment International Limited:

Primary Outcome Measures:
  • Tumor response [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    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


Secondary Outcome Measures:
  • Overall Survival [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    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 to Progression [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Plasma arginase level [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    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

  • Quality of Life [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    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.

  • Plasma arginine levels [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    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


Enrollment: 20
Study Start Date: March 2010
Study Completion Date: February 2012
Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: PEG-BCT-100
Pegylated Recombinant Human Arginase I
Biological: Pegylated Recombinant Human Arginase I
Weekly dose of PEG-BCT-100 for at least 8 weeks (or until disease progression) at 1600U/kg
Other Name: PEG-BCT-100

Detailed Description:

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
  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Confirmed diagnosis of HCC according to the European Association for the Study of the Liver criteria
  • Known underlying HCC etiology specified by hepatitis B, hepatitis C, post alcoholic cirrhosis, or other
  • HCC lesion(s) which are not resectable and which are measurable by C-T scan
  • Progression of or non-response of HCC lesions after treatments which are considered best standard of care - surgical resection, radiofrequency ablation, chemoembolization
  • No cancer treatment or surgery within the prior 4 weeks, either chemotherapy, targeted biologic or enzymes, either approved or investigational;
  • Males or females from 18 to 75 years-old, inclusive;
  • Ability and willingness to provide written informed consent;
  • Karnofsky performance status of 80% or above and expected survival of more than 12 weeks; and,
  • Negative urine pregnancy test, if female, and willingness to use an effective method of contraception during the entire study period
  • No cognitive impairment
  • Ability to understand and read Chinese

Exclusion Criteria:

  • Advancing liver failure indicated by uncontrolled ascites, pleural effusions, encephalopathy, or a Child-Pugh score of C
  • Significant hepatic, renal or bone marrow dysfunction indicated by total bilirubin >40 µmol/L, evidence of bile duct obstruction, serum albumin <30 g/L, serum SGOT >5 x upper limit of normal, ANC <1.0 x 10^9/L, platelets <100 x 10^9/L, or INR >2.0
  • Significant cardiac or pulmonary disease defined by New York Heart Association (NYHA) Class III or IV, VEF <50% by echo or MUGA, or a history of myocardial infarction within the past 6 months, significant unstable arrhythmia or evidence of ischemia on ECG
  • Pregnant or nursing women. NOTE: Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
  • Significant active infection including HIV requiring oral or parenteral anti-infective therapies;
  • Use of investigational drug(s) within 4 weeks of enrollment; or,
  • Prior treatment with arginine depleting agent.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01092091

Locations
Hong Kong
Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The University of Hong Kong
Hong Kong, Hong Kong
Sponsors and Collaborators
Bio-Cancer Treatment International Limited
The University of Hong Kong
Chinese University of Hong Kong
Investigators
Principal Investigator: Ronnie TP Poon, Prof Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The University of Hong Kong
  More Information

No publications provided

Responsible Party: Bio-Cancer Treatment International Limited
ClinicalTrials.gov Identifier: NCT01092091     History of Changes
Other Study ID Numbers: HKCTR-503C, PR/CT0299/2009
Study First Received: March 23, 2010
Last Updated: March 13, 2012
Health Authority: Hong Kong: Department of Health

Keywords provided by Bio-Cancer Treatment International Limited:
Neoplasm
Hepatocellular Carcinoma

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Hepatocellular
Neoplasms
Adenocarcinoma
Digestive System Diseases
Digestive System Neoplasms
Liver Diseases
Liver Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on October 29, 2014