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

Phase 3

Completed

Conditions: Hepatocellular Carcinoma

Interventions: Drug: ADI-PEG 20 (arginine deiminase formulated with polyethylene glycol)
Drug: Placebo
Other: Best Supportive Care

Registration Number: NCT01287585

Lead Sponsor: 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.

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).

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 636

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Best Supportive Care	an inert treatment with no therapeutic value.
ADI-PEG 20	ADI-PEG 20 (arginine deiminase formulated with polyethylene glycol)	Arginine deiminase formulated with polyethylene glycol.
ADI-PEG 20	Best Supportive Care	Arginine deiminase formulated with polyethylene glycol.
Placebo	Placebo	an inert treatment with no therapeutic value.

Primary Outcome Measures

Name	Time	Method
Overall survival	18 months	Overall survival - until death or study closure.

Secondary Outcome Measures

Name	Time	Method
Safety and tolerability - number of participants with adverse events.	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.

Trial Locations

Locations (73): CMMC-LY
🇨🇳
Tainan City, Taiwan
CGMHCY
🇨🇳
ChiaYi, Taiwan
Kaohsiung Medical University Chung-Ho Memorial Hospital
🇨🇳
Kaohsiung City, Taiwan
Chang Gung Medical Foundation-Kaohsiung
🇨🇳
Kaohsiung County, Taiwan
Mackay Memorial Hospital-Taipei Branch
🇨🇳
Taipei, Taiwan
China Medicine University Hospital
🇨🇳
Taichung, Taiwan
CMMC-YK
🇨🇳
Tainan City, Taiwan
National Cheng Kung University Hospital
🇨🇳
Tainan, Taiwan
Taipei Veterans General Hospital
🇨🇳
Taipei, Taiwan
Chang Gung Medical Foundation-Linkou
🇨🇳
Taoyuan County, Taiwan
Drexel University
🇺🇸
Philadelphia, Pennsylvania, United States
Pacific Medical Center
🇺🇸
San Francisco, California, United States
University of Minnesota Cancer Center
🇺🇸
Minneapolis, Minnesota, United States
No. 156 North Road of West Second Ring
🇨🇳
Gulou District, Fujian, China
Clatterbridge Cancer Center
🇬🇧
Bebington, United Kingdom
King's College Hospital
🇬🇧
London, United Kingdom
University of Maryland Greenbaum Cancer Center
🇺🇸
Baltimore, Maryland, United States
Michael E. DeBakey VA Medical Center
🇺🇸
Houston, Texas, United States
15th Floor, In-patient Building (East), No. 651 Dongfeng East Road
🇨🇳
Guangzhou, Guangdong, China
University of Pennsylvania Abramson Cancer Center
🇺🇸
Philadelphia, Pennsylvania, United States
The First Hospital of Medical University Of Anhui
🇨🇳
Hefei, Anhui, China
5th Fl, Inpatient Bldg, No. 71, Heti Rd
🇨🇳
Qingxiu Disttrict, Guangxi, China
Samsung Medical Center
🇰🇷
Seoul, Korea, Republic of
Piedmont Research Institute
🇺🇸
Atlanta, Georgia, United States
University of California at San Diego Moores Cancer Center
🇺🇸
San Diego, California, United States
Korea University Anam Hospital
🇰🇷
Seoul, Korea, Republic of
University of Washington
🇺🇸
Seattle, Washington, United States
A ward of Oncology-287 Changhuai Rd
🇨🇳
Bengbu, Anhui, China
5th Fl, Inpatient Bldg, No. 8,
🇨🇳
Fengtai Distrcit, Beijing, China
Southern California Research Center
🇺🇸
Coronado, California, United States
Asan Medical Center
🇰🇷
Seoul, Korea, Republic of
Northern Taiwan University Hospital
🇨🇳
Taipei City, Taiwan
UT Southwestern
🇺🇸
Dallas, Texas, United States
Christie NHS Trust
🇬🇧
Manchester, United Kingdom
Royal Marsden
🇬🇧
Sutton, United Kingdom
The Chinese people's liberation army 81 hospital
🇨🇳
Nanjing, Jiangsu, China
Seoul St. Mary's Hospital
🇰🇷
Seoul, Korea, Republic of
Severance Hospital
🇰🇷
Seoul, Korea, Republic of
Royal Free Hospital
🇬🇧
London, United Kingdom
Hammersmith Hospital
🇬🇧
London, United Kingdom
St. Bartholomew's Hospital
🇬🇧
London, United Kingdom
University Hospitals Birmingham NHS Foundation Trust
🇬🇧
Birmingham, United Kingdom
Nottingham University Hospital
🇬🇧
Nottingham, United Kingdom
Oncology, No. 678, Furong Rd
🇨🇳
Hefei, Anhui, China
University of Hawaii
🇺🇸
Honolulu, Hawaii, United States
Azienda Ospedaliera di Padova
🇮🇹
Padova, Italy
Azienda Ospedaliera San Camillo Forlanini
🇮🇹
Roma, Italy
Instituto Nazionale pler le Malattie Infettive
🇮🇹
Rome, Italy
Catherine Frenette
🇺🇸
La Jolla, California, United States
Stanford University
🇺🇸
Palo Alto, California, United States
University of Alabama
🇺🇸
Birmingham, Alabama, United States
Nebraska Hem-Onc
🇺🇸
Lincoln, Nebraska, United States
Johns Hopkins University Hospital
🇺🇸
Baltimore, Maryland, United States
Wayne State University School of Medicine, Dept Oncology
🇺🇸
Detroit, Michigan, United States
UPMC Cancer Centers
🇺🇸
Pittsburgh, Pennsylvania, United States
3rd Floor, Medicine Building, No. 150 Haping Rd
🇨🇳
Harbin, Heilongjiang, China
Oncology, 185 Road Juqian Street
🇨🇳
Changzhou, Jiangsu, China
5th Floor, Medical Building, No. 1018 Huguang Rd
🇨🇳
Changchun, Jilin, China
No. 193, Lianhe Rd, Shahekou Dist.
🇨🇳
Dalian, Liaoning, China
No. 596, Xinsi Rd., Baqiao Dist.
🇨🇳
Xi'an, Shaanxi, China
Floor 7, 3rd Inpatient Building No. 37, Guoxue Xiang
🇨🇳
Cheng Du, Sichuan, China
13th Floor, Internal Medicine Building, No. 29 Gaotanyan Main St.
🇨🇳
ChongQing, China
Istituto Tumori "Giovanni Paolo II"
🇮🇹
Bari, Italy
Azienda Ospedaliera Niguarda Cà Granda
🇮🇹
Milan, Italy
Bldg No. 5, 3rd Floor, Dongan Rd
🇨🇳
Shanghai, China
Fondazione Centro San Raffaele del Monte Tabor
🇮🇹
Milan, Italy
Policlinico S. Orsola-Malpighi
🇮🇹
Bologna, 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
The Royal Marsden Hospital
🇬🇧
London, United Kingdom
Memorial Sloan-Kettering Cancer Center
🇺🇸
New York, New York, United States
University of Oregon
🇺🇸
Portland, Oregon, United States