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Study of Pegylated Human Recombinant Arginase for Liver Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00988195
Recruitment Status : Completed
First Posted : October 2, 2009
Last Update Posted : March 14, 2012
The University of Hong Kong
Chinese University of Hong Kong
Information provided by (Responsible Party):
Bio-Cancer Treatment International Limited

Brief Summary:
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 or disease Intervention/treatment Phase
Neoplasm Hepatocellular Carcinoma Biological: Pegylated Recombinant Human Arginase I Drug: Doxorubicin Phase 1

Detailed Description:

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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 15 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Recombinant Human Arginase I (rhArgI) for Patients With Advanced Hepatocellular Carcinoma (HCC): An Adaptive Design Dose Escalation Trial With Addition of Standard Doxorubicin Treatment
Study Start Date : May 2008
Actual Primary Completion Date : August 2009
Actual Study Completion Date : August 2009

Resource links provided by the National Library of Medicine

Drug Information available for: Doxorubicin

Arm Intervention/treatment
Experimental: PEG-BCT-100
Pegylated Recombinant Human Arginase I
Biological: Pegylated Recombinant Human Arginase I
Week 1 (Single Dose); Weeks 3 - 11 (Weekly Dose x 8 weeks)in 8 escalation doses
Other Name: PEG-BCT-100

Drug: Doxorubicin
Weeks 13-24 (once every 3 weeks)
Other Name: Adriamycin

Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. Overall Survival, Time to Progression [ Time Frame: 24 weeks ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00988195

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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
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Principal Investigator: Ronnie TP Poon, Prof Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The University of Hong Kong
Additional Information:
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Responsible Party: Bio-Cancer Treatment International Limited
ClinicalTrials.gov Identifier: NCT00988195    
Other Study ID Numbers: HKCTR-503
PR/CT205/07 ( Other Identifier: Department of Health, HKSAR )
First Posted: October 2, 2009    Key Record Dates
Last Update Posted: March 14, 2012
Last Verified: March 2012
Keywords provided by Bio-Cancer Treatment International Limited:
Hepatocellular Carcinoma
Additional relevant MeSH terms:
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Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Antibiotics, Antineoplastic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action