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 May 2014 by Polaris Group
Sponsor:
Information provided by (Responsible Party):
Polaris Group
ClinicalTrials.gov Identifier:
NCT01287585
First received: January 25, 2011
Last updated: May 8, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Hepatocellular Carcinoma
Drug: ADI-PEG 20 (arginine deiminase formulated with polyethylene glycol)
Drug: Placebo
Phase 3

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

Resource links provided by NLM:


Further study details as provided by Polaris Group:

Primary Outcome Measures:
  • Overall survival [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    Overall survival - until death or study closure.


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 633
Study Start Date: July 2011
Estimated Study Completion Date: March 2016
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ADI-PEG 20
Arginine deiminase formulated with polyethylene glycol.
Drug: ADI-PEG 20 (arginine deiminase formulated with polyethylene glycol)
18 mg/m2, weekly, intramuscular, until disease progression or toxicity.
Placebo Comparator: Placebo Drug: Placebo
weekly, intramuscular, until disease progression or toxicity.

Detailed Description:

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).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01287585

Contacts
Contact: John S Bomalaski, M.D. 858-452-6688 ext 114 jbomalaski@polarispharma.com

  Show 73 Study Locations
Sponsors and Collaborators
Polaris Group
Investigators
Study Director: John S Bomalaski, M.D. Polaris Group
  More Information

No publications provided

Responsible Party: Polaris Group
ClinicalTrials.gov Identifier: NCT01287585     History of Changes
Other Study ID Numbers: POLARIS2009-001
Study First Received: January 25, 2011
Last Updated: May 8, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Polaris Group:
Hepatocellular carcinoma
Arginine
Arginine deiminase
ADI-PEG 20

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases

ClinicalTrials.gov processed this record on August 28, 2014