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

Phase 1
18 Years
75 Years
Not Enrolling
Neoplasm, Hepatocellular Carcinoma

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Trial Information

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 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-

- 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

- 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

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,

- 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 ┬Ámol/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

- 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.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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

Outcome Time Frame:

24 weeks

Safety Issue:


Principal Investigator

Ronnie TP Poon, Prof

Investigator Role:

Principal Investigator

Investigator Affiliation:

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


Hong Kong: Department of Health

Study ID:




Start Date:

May 2008

Completion Date:

August 2009

Related Keywords:

  • Neoplasm
  • Hepatocellular Carcinoma
  • Neoplasm
  • Hepatocellular Carcinoma
  • Neoplasms
  • Carcinoma
  • Carcinoma, Hepatocellular