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Study of Pegylated Human Recombinant Arginase for Liver Cancer

Primary Purpose

Neoplasm, Hepatocellular Carcinoma

Status
Completed
Phase
Phase 1
Locations
Hong Kong
Study Type
Interventional
Intervention
Pegylated Recombinant Human Arginase I
Doxorubicin
Sponsored by
Bio-Cancer Treatment International Limited
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Neoplasm focused on measuring Neoplasm, Hepatocellular Carcinoma

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The University of Hong Kong

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

PEG-BCT-100

Arm Description

Pegylated Recombinant Human Arginase I

Outcomes

Primary Outcome Measures

Plasma arginase and arginine levels,as well as tumour response, i.e. an effect on growth in the milieu of arginine depletion.

Secondary Outcome Measures

Overall Survival, Time to Progression

Full Information

First Posted
September 30, 2009
Last Updated
March 13, 2012
Sponsor
Bio-Cancer Treatment International Limited
Collaborators
The University of Hong Kong, Chinese University of Hong Kong
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1. Study Identification

Unique Protocol Identification Number
NCT00988195
Brief Title
Study of Pegylated Human Recombinant Arginase for Liver Cancer
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 Type
Interventional

2. Study Status

Record Verification Date
March 2012
Overall Recruitment Status
Completed
Study Start Date
May 2008 (undefined)
Primary Completion Date
August 2009 (Actual)
Study Completion Date
August 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bio-Cancer Treatment International Limited
Collaborators
The University of Hong Kong, Chinese University of Hong Kong

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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).
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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neoplasm, Hepatocellular Carcinoma
Keywords
Neoplasm, Hepatocellular Carcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Actual)

8. Arms, Groups, and Interventions

Arm Title
PEG-BCT-100
Arm Type
Experimental
Arm Description
Pegylated Recombinant Human Arginase I
Intervention Type
Biological
Intervention Name(s)
Pegylated Recombinant Human Arginase I
Other Intervention Name(s)
PEG-BCT-100
Intervention Description
Week 1 (Single Dose); Weeks 3 - 11 (Weekly Dose x 8 weeks)in 8 escalation doses
Intervention Type
Drug
Intervention Name(s)
Doxorubicin
Other Intervention Name(s)
Adriamycin
Intervention Description
Weeks 13-24 (once every 3 weeks)
Primary Outcome Measure Information:
Title
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 Measure Information:
Title
Overall Survival, Time to Progression
Time Frame
24 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility 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 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ronnie TP Poon, Prof
Organizational Affiliation
Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The University of Hong Kong
Official's Role
Principal Investigator
Facility Information:
Facility Name
Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The University of Hong Kong
City
Hong Kong
Country
Hong Kong

12. IPD Sharing Statement

Links:
URL
http://www.hkclinicaltrials.com/
Description
HKCTR-503

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Study of Pegylated Human Recombinant Arginase for Liver Cancer

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