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A Randomized, Double-Blind, Multi-Center Phase 3 Study of ADI-PEG 20 Plus Best Supportive Care (BSC) Versus Placebo Plus BSC in Subjects With Advanced Hepatocellular Carcinoma (HCC) Who Have Failed Prior Systemic Therapy

Phase 3
18 Years
Open (Enrolling)
Hepatocellular Carcinoma

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Trial Information

A Randomized, Double-Blind, Multi-Center Phase 3 Study of ADI-PEG 20 Plus Best Supportive Care (BSC) Versus Placebo Plus BSC in Subjects With Advanced Hepatocellular Carcinoma (HCC) Who Have Failed Prior Systemic Therapy

Patients will be randomized 2:1 to study drug versus placebo. Patients will be recruited
from North American, Europe and Asia. In addition to overall survival, progression free
survival, responses by RECIST 1.1 criteria and time to tumor progression will be calculated.
Safety and tolerability will be assessed, as will pharmacodynamics (peripheral blood levels
of arginine and citrulline), pharmacokinetics (peripheral blood levels of ADI-PEG 20) and
immunogenicity (antibodies to ADI-PEG 20).

Inclusion Criteria:

- Prior diagnosis of HCC confirmed histologically.

- Prior treatment with at least 1 systemic agent, with documented progressive disease
after systemic agent(s), or adverse event(s)associated with prior systemic agent(s)
that resulted in discontinuance of that agent(s).

- Cirrhotic status of Child-Pugh grade B7.

- Expected survival of at least 3 months.

- Adequate hematologic, hepatic, and renal function.

Exclusion Criteria:

- Candidate for potential curative therapies (i.e., resection or transplantation) or
loco-regional approaches (i.e., ablation, embolization).

- Significant cardiac disease.

- Serious infection requiring treatment with systemically administered antibiotics.

- Pregnancy or lactation.

- Expected non-compliance.

- Uncontrolled intercurrent illness, or psychiatric illness or social situations that
would limit compliance with study requirements.

- Subjects who have had any anticancer treatment within 2 weeks prior to entering the

- Subjects who have not fully recovered from toxicities associated with previous HCC
loco-regional or systemic therapies.

- Subjects with history of another primary cancer, with the exception of: a) curatively
resected non-melanoma skin cancer; b) curatively treated cervical carcinoma in situ;
or c) other primary solid tumor with no known active disease present in the opinion
of the investigator will not affect patient outcome in the setting of current HCC

- Allergy to pegylated products.

- Bleeding esophageal or gastric varices within the prior three months, except if
banded or treated.

- Subjects known to be HIV positive.

- Uncontrolled ascites (defined as not easily controlled with diuretic treatment).

- Having received any blood transfusion, blood component preparation, erythropoietin,
albumin preparation, or granulocyte colony stimulating factors (G-CSF) within 7 days
prior to screening laboratories or after screening laboratories have been obtained
until first dose of study drug or placebo.

- Use of traditional medicines approved by local authorities, including but not limited
to Chinese herbs within 14 days of first dose of study drug or placebo.

- ECOG performance status > 2.

- Prior allograft,including liver transplant.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Outcome Measure:

Overall survival

Outcome Description:

Overall survival - until death or study closure.

Outcome Time Frame:

18 months

Safety Issue:


Principal Investigator

John S Bomalaski, M.D.

Investigator Role:

Study Director

Investigator Affiliation:

Polaris Group


United States: Food and Drug Administration

Study ID:




Start Date:

July 2011

Completion Date:

July 2014

Related Keywords:

  • Hepatocellular Carcinoma
  • Hepatocellular carcinoma
  • Arginine
  • Arginine deiminase
  • ADI-PEG 20
  • Carcinoma
  • Carcinoma, Hepatocellular



University of Alabama Birmingham, Alabama  
Memorial Sloan-Kettering Cancer Center New York, New York  10021
University of Minnesota Cancer Center Minneapolis, Minnesota  55455
Stanford University Stanford, California  94305
University of Washington Seattle, Washington  98195
University of Maryland Greenbaum Cancer Center Baltimore, Maryland  21201
University of Pennsylvania Abramson Cancer Center Philadelphia, Pennsylvania  19104
University of Hawaii Honolulu, Hawaii  96813
Michael E. DeBakey VA Medical Center Houston, Texas  77030
Drexel University Philadelphia, Pennsylvania  19104
University of California at San Diego Moores Cancer Center San Diego, California  
Pacific Medical Center San Francisco, California  
Piedmont Research Institute Atlanta, Georgia  
Johns Hopkins University Hospital Baltimore, Maryland  
University of Oregon Portland, Oregon