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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01287585
Recruitment Status : Completed
First Posted : February 1, 2011
Last Update Posted : September 18, 2018
Information provided by (Responsible Party):
Polaris Group

Brief Summary:
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 or disease Intervention/treatment Phase
Hepatocellular Carcinoma Drug: ADI-PEG 20 (arginine deiminase formulated with polyethylene glycol) Drug: Placebo Phase 3

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).

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 636 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, 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
Study Start Date : July 2011
Actual Primary Completion Date : July 2015
Actual Study Completion Date : July 2015

Resource links provided by the National Library of Medicine

Drug Information available for: Arginine

Arm Intervention/treatment
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.

Primary Outcome Measures :
  1. Overall survival [ Time Frame: 18 months ]
    Overall survival - until death or study closure.

Secondary Outcome Measures :
  1. Safety and tolerability - number of participants with adverse events. [ Time Frame: 18 months - at anticipated end of study. ]
    In addition to safety and tolerability, progression free survival, response rate using RECIST 1.1 and time to tumor progression will be assessed.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01287585

  Hide Study Locations
United States, Alabama
University of Alabama
Birmingham, Alabama, United States
United States, California
Southern California Research Center
Coronado, California, United States, 92118
Catherine Frenette
La Jolla, California, United States, 92037
Stanford University
Palo Alto, California, United States
University of California at San Diego Moores Cancer Center
San Diego, California, United States
Pacific Medical Center
San Francisco, California, United States
United States, Georgia
Piedmont Research Institute
Atlanta, Georgia, United States
United States, Hawaii
University of Hawaii
Honolulu, Hawaii, United States
United States, Maryland
University of Maryland Greenbaum Cancer Center
Baltimore, Maryland, United States, 21201
Johns Hopkins University Hospital
Baltimore, Maryland, United States
United States, Michigan
Wayne State University School of Medicine, Dept Oncology
Detroit, Michigan, United States, 48201
United States, Minnesota
University of Minnesota Cancer Center
Minneapolis, Minnesota, United States
United States, Nebraska
Nebraska Hem-Onc
Lincoln, Nebraska, United States
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
United States, Oregon
University of Oregon
Portland, Oregon, United States
United States, Pennsylvania
Drexel University
Philadelphia, Pennsylvania, United States
University of Pennsylvania Abramson Cancer Center
Philadelphia, Pennsylvania, United States
UPMC Cancer Centers
Pittsburgh, Pennsylvania, United States
United States, Texas
UT Southwestern
Dallas, Texas, United States
Michael E. DeBakey VA Medical Center
Houston, Texas, United States
United States, Washington
University of Washington
Seattle, Washington, United States
China, Anhui
A ward of Oncology-287 Changhuai Rd
Bengbu, Anhui, China, 233000
Oncology, No. 678, Furong Rd
Hefei, Anhui, China, 230601
The First Hospital of Medical University Of Anhui
Hefei, Anhui, China
China, Beijing
5th Fl, Inpatient Bldg, No. 8,
Fengtai Distrcit, Beijing, China, 100071
China, Fujian
No. 156 North Road of West Second Ring
Gulou District, Fujian, China, 350025
China, Guangdong
15th Floor, In-patient Building (East), No. 651 Dongfeng East Road
Guangzhou, Guangdong, China, 510060
China, Guangxi
5th Fl, Inpatient Bldg, No. 71, Heti Rd
Qingxiu Disttrict, Guangxi, China, 530021
China, Heilongjiang
3rd Floor, Medicine Building, No. 150 Haping Rd
Harbin, Heilongjiang, China, 150040
China, Jiangsu
Oncology, 185 Road Juqian Street
Changzhou, Jiangsu, China, 213003
The Chinese people's liberation army 81 hospital
Nanjing, Jiangsu, China
China, Jilin
5th Floor, Medical Building, No. 1018 Huguang Rd
Changchun, Jilin, China, 116011
China, Liaoning
No. 193, Lianhe Rd, Shahekou Dist.
Dalian, Liaoning, China, 116011
China, Shaanxi
No. 596, Xinsi Rd., Baqiao Dist.
Xi'an, Shaanxi, China, 710038
China, Sichuan
Floor 7, 3rd Inpatient Building No. 37, Guoxue Xiang
Cheng Du, Sichuan, China, 610041
13th Floor, Internal Medicine Building, No. 29 Gaotanyan Main St.
ChongQing, China, 400038
Bldg No. 5, 3rd Floor, Dongan Rd
Shanghai, China
Istituto Tumori "Giovanni Paolo II"
Bari, Italy
Policlinico S. Orsola-Malpighi
Bologna, Italy
Azienda Ospedaliera Niguarda Cà Granda
Milan, Italy
Fondazione Centro San Raffaele del Monte Tabor
Milan, Italy
Fondazione IRCCs "Ca Granda" Ospedale Maggiore Policlinico
Milan, Italy
Policlinico di Monza
Monza, Italy
Istituto Nazionale per lo Studio e la Cura dei Tumori
Naples, Italy
Azienda Ospedaliera di Padova
Padova, Italy
Azienda Ospedaliera San Camillo Forlanini
Roma, Italy
Instituto Nazionale pler le Malattie Infettive
Rome, Italy
Korea, Republic of
Asan Medical Center
Seoul, Korea, Republic of
Korea University Anam Hospital
Seoul, Korea, Republic of
Samsung Medical Center
Seoul, Korea, Republic of
Seoul St. Mary's Hospital
Seoul, Korea, Republic of
Severance Hospital
Seoul, Korea, Republic of
ChiaYi, Taiwan
Kaohsiung Medical University Chung-Ho Memorial Hospital
Kaohsiung City, Taiwan
Chang Gung Medical Foundation-Kaohsiung
Kaohsiung County, Taiwan
China Medicine University Hospital
Taichung, Taiwan, 40447
Tainan City, Taiwan
Tainan City, Taiwan
National Cheng Kung University Hospital
Tainan, Taiwan
Northern Taiwan University Hospital
Taipei City, Taiwan
Mackay Memorial Hospital-Taipei Branch
Taipei, Taiwan
Taipei Veterans General Hospital
Taipei, Taiwan
Chang Gung Medical Foundation-Linkou
Taoyuan County, Taiwan
United Kingdom
Clatterbridge Cancer Center
Bebington, United Kingdom
University Hospitals Birmingham NHS Foundation Trust
Birmingham, United Kingdom
Hammersmith Hospital
London, United Kingdom
King's College Hospital
London, United Kingdom
Royal Free Hospital
London, United Kingdom
St. Bartholomew's Hospital
London, United Kingdom
The Royal Marsden Hospital
London, United Kingdom
Christie NHS Trust
Manchester, United Kingdom
Nottingham University Hospital
Nottingham, United Kingdom
Royal Marsden
Sutton, United Kingdom
Sponsors and Collaborators
Polaris Group
Study Director: John S Bomalaski, M.D. Polaris Group

Additional Information:
Abou-Alfa GK, Qin S, Ryoo BY, Lu SN, Yen C-J, Feng YH, Lim HY, Izzo F, Colombo M, Sarker D, Bolondi L, Vaccaro GM, Harris WP, Chen Z, Hubner R, Meyer T, Bomalaski JS, Lin CC, Chao Y, Chen LZ. 2016. Phase III randomized study of second line ADI-peg 20 (A) plus best supportive care versus placebo (P) plus best supportive care in patients (pts) with advanced hepatocellular carcinoma (HCC). J Clin Oncol 34, 2016 (suppl; abstr 4017).

Responsible Party: Polaris Group Identifier: NCT01287585     History of Changes
Other Study ID Numbers: POLARIS2009-001
First Posted: February 1, 2011    Key Record Dates
Last Update Posted: September 18, 2018
Last Verified: August 2016

Keywords provided by Polaris Group:
Hepatocellular carcinoma
Arginine deiminase

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