Ph 3 ADI-PEG 20 Versus Placebo in Subjects With Advanced Hepatocellular Carcinoma Who Have Failed Prior Systemic Therapy

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Polaris Group
Sponsor:
Information provided by (Responsible Party):
Polaris Group
ClinicalTrials.gov Identifier:
NCT01287585
First received: January 25, 2011
Last updated: September 9, 2014
Last verified: September 2014

January 25, 2011
September 9, 2014
July 2011
December 2015   (final data collection date for primary outcome measure)
Overall survival [ Time Frame: 18 months ] [ Designated as safety issue: No ]
Overall survival - until death or study closure.
Same as current
Complete list of historical versions of study NCT01287585 on ClinicalTrials.gov Archive Site
Safety and tolerability - number of participants with adverse events. [ Time Frame: 18 months - at anticipated end of study. ] [ Designated as safety issue: Yes ]
In addition to safety and tolerability, progression free survival, response rate using RECIST 1.1 and time to tumor progression will be assessed.
Same as current
Not Provided
Not Provided
 
Ph 3 ADI-PEG 20 Versus Placebo in Subjects With Advanced Hepatocellular Carcinoma Who Have Failed Prior Systemic Therapy
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

This is a study of ADI-PEG 20 (pegylated arginine deiminase), an arginine degrading enzyme versus placebo in patients with hepatocellular carcinoma who have failed prior systemic treatment (chemotherapy). Hepatocellular carcinomas have been found to require arginine, an amino acid. Thus the hypothesis is that by restricting arginine with ADI-PEG 20, the hepatocellular carcinoma cells will starve and die.

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).

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Hepatocellular Carcinoma
  • Drug: ADI-PEG 20 (arginine deiminase formulated with polyethylene glycol)
    18 mg/m2, weekly, intramuscular, until disease progression or toxicity.
  • Drug: Placebo
    weekly, intramuscular, until disease progression or toxicity.
  • Experimental: ADI-PEG 20
    Arginine deiminase formulated with polyethylene glycol.
    Intervention: Drug: ADI-PEG 20 (arginine deiminase formulated with polyethylene glycol)
  • Placebo Comparator: Placebo
    Intervention: Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
633
March 2016
December 2015   (final data collection date for primary outcome measure)

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 study.
  • 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 diagnosis.
  • 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.
Both
18 Years and older
No
Contact: John S Bomalaski, M.D. 858-452-6688 ext 114 jbomalaski@polarispharma.com
China,   Korea, Republic of,   Italy,   United States,   Taiwan,   United Kingdom
 
NCT01287585
POLARIS2009-001
Yes
Polaris Group
Polaris Group
Not Provided
Study Director: John S Bomalaski, M.D. Polaris Group
Polaris Group
September 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP