Ph 3 ADI-PEG 20 Versus Placebo in Subjects With Advanced Hepatocellular Carcinoma Who Have Failed Prior Systemic Therapy
ADI-PEG 20
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
1 other identifier
interventional
636
6 countries
73
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3 hepatocellular-carcinoma
Started Jul 2011
73 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 25, 2011
CompletedFirst Posted
Study publicly available on registry
February 1, 2011
CompletedStudy Start
First participant enrolled
July 1, 2011
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 1, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
July 1, 2015
CompletedSeptember 6, 2019
August 1, 2016
4 years
January 25, 2011
August 27, 2019
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Overall survival
Overall survival - until death or study closure.
18 months
Secondary Outcomes (1)
Safety and tolerability - number of participants with adverse events.
18 months - at anticipated end of study.
Study Arms (2)
ADI-PEG 20
EXPERIMENTALArginine deiminase formulated with polyethylene glycol.
Placebo
PLACEBO COMPARATORan inert treatment with no therapeutic value.
Interventions
18 mg/m2, weekly, intramuscular, until disease progression or toxicity.
treatment of disease-related symptoms throughout the study.
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
- +2 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Polaris Grouplead
Study Sites (73)
University of Alabama
Birmingham, Alabama, United States
Southern California Research Center
Coronado, California, 92118, United States
Catherine Frenette
La Jolla, California, 92037, United States
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
Piedmont Research Institute
Atlanta, Georgia, United States
University of Hawaii
Honolulu, Hawaii, United States
University of Maryland Greenbaum Cancer Center
Baltimore, Maryland, 21201, United States
Johns Hopkins University Hospital
Baltimore, Maryland, United States
Wayne State University School of Medicine, Dept Oncology
Detroit, Michigan, 48201, United States
University of Minnesota Cancer Center
Minneapolis, Minnesota, United States
Nebraska Hem-Onc
Lincoln, Nebraska, United States
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065, United States
University of Oregon
Portland, Oregon, United States
Drexel University
Philadelphia, Pennsylvania, United States
University of Pennsylvania Abramson Cancer Center
Philadelphia, Pennsylvania, United States
UPMC Cancer Centers
Pittsburgh, Pennsylvania, United States
UT Southwestern
Dallas, Texas, United States
Michael E. DeBakey VA Medical Center
Houston, Texas, United States
University of Washington
Seattle, Washington, United States
A ward of Oncology-287 Changhuai Rd
Bengbu, Anhui, 233000, China
Oncology, No. 678, Furong Rd
Hefei, Anhui, 230601, China
The First Hospital of Medical University Of Anhui
Hefei, Anhui, China
5th Fl, Inpatient Bldg, No. 8,
Fengtai Distrcit, Beijing Municipality, 100071, China
No. 156 North Road of West Second Ring
Gulou District, Fujian, 350025, China
15th Floor, In-patient Building (East), No. 651 Dongfeng East Road
Guangzhou, Guangdong, 510060, China
5th Fl, Inpatient Bldg, No. 71, Heti Rd
Qingxiu Disttrict, Guangxi, 530021, China
3rd Floor, Medicine Building, No. 150 Haping Rd
Harbin, Heilongjiang, 150040, China
Oncology, 185 Road Juqian Street
Changzhou, Jiangsu, 213003, China
The Chinese people's liberation army 81 hospital
Nanjing, Jiangsu, China
5th Floor, Medical Building, No. 1018 Huguang Rd
Changchun, Jilin, 116011, China
No. 193, Lianhe Rd, Shahekou Dist.
Dalian, Liaoning, 116011, China
No. 596, Xinsi Rd., Baqiao Dist.
Xi'an, Shaanxi, 710038, China
Floor 7, 3rd Inpatient Building No. 37, Guoxue Xiang
Chengdu, Sichuan, 610041, China
13th Floor, Internal Medicine Building, No. 29 Gaotanyan Main St.
Chongqing, 400038, China
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 CĂ 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
Padua, Italy
Azienda Ospedaliera San Camillo Forlanini
Roma, Italy
Instituto Nazionale pler le Malattie Infettive
Rome, Italy
Asan Medical Center
Seoul, South Korea
Korea University Anam Hospital
Seoul, South Korea
Samsung Medical Center
Seoul, South Korea
Seoul St. Mary's Hospital
Seoul, South Korea
Severance Hospital
Seoul, South Korea
CGMHCY
Chiayi City, Taiwan
Kaohsiung Medical University Chung-Ho Memorial Hospital
Kaohsiung City, Taiwan
Chang Gung Medical Foundation-Kaohsiung
Kaohsiung County, Taiwan
China Medicine University Hospital
Taichung, 40447, Taiwan
CMMC-LY
Tainan, Taiwan
CMMC-YK
Tainan, Taiwan
National Cheng Kung University Hospital
Tainan, Taiwan
Mackay Memorial Hospital-Taipei Branch
Taipei, Taiwan
Northern Taiwan University Hospital
Taipei, Taiwan
Taipei Veterans General Hospital
Taipei, Taiwan
Chang Gung Medical Foundation-Linkou
Taoyuan, Taiwan
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
Related Publications (1)
Abou-Alfa GK, Qin S, Ryoo BY, Lu SN, Yen CJ, Feng YH, Lim HY, Izzo F, Colombo M, Sarker D, Bolondi L, Vaccaro G, Harris WP, Chen Z, Hubner RA, Meyer T, Sun W, Harding JJ, Hollywood EM, Ma J, Wan PJ, Ly M, Bomalaski J, Johnston A, Lin CC, Chao Y, Chen LT. Phase III randomized study of second line ADI-PEG 20 plus best supportive care versus placebo plus best supportive care in patients with advanced hepatocellular carcinoma. Ann Oncol. 2018 Jun 1;29(6):1402-1408. doi: 10.1093/annonc/mdy101.
PMID: 29659672BACKGROUND
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
John S Bomalaski, M.D.
Polaris Group
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 25, 2011
First Posted
February 1, 2011
Study Start
July 1, 2011
Primary Completion
July 1, 2015
Study Completion
July 1, 2015
Last Updated
September 6, 2019
Record last verified: 2016-08