Study of Pegylated Human Recombinant Arginase for Liver Cancer

Recombinant Human Arginase I (rhArgI) for Patients With Advanced Hepatocellular Carcinoma (HCC): An Adaptive Design Dose Escalation Trial With Addition of Standard Doxorubicin Treatment

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).

Study Overview

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

Study Type

Interventional

Enrollment (Actual)

15

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: PEG-BCT-100
Pegylated Recombinant Human Arginase I
Week 1 (Single Dose); Weeks 3 - 11 (Weekly Dose x 8 weeks)in 8 escalation doses
Other Names:
  • PEG-BCT-100
Weeks 13-24 (once every 3 weeks)
Other Names:
  • Adriamycin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
24 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
Overall Survival, Time to Progression
Time Frame: 24 weeks
24 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2008

Primary Completion (ACTUAL)

August 1, 2009

Study Completion (ACTUAL)

August 1, 2009

Study Registration Dates

First Submitted

September 30, 2009

First Submitted That Met QC Criteria

September 30, 2009

First Posted (ESTIMATE)

October 2, 2009

Study Record Updates

Last Update Posted (ESTIMATE)

March 14, 2012

Last Update Submitted That Met QC Criteria

March 13, 2012

Last Verified

March 1, 2012

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Hepatocellular Carcinoma

Clinical Trials on Pegylated Recombinant Human Arginase I

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