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

Primary Purpose

Hepatocellular Carcinoma

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
ADI-PEG 20 (arginine deiminase formulated with polyethylene glycol)
Placebo
Best Supportive Care
Sponsored by
Polaris Group
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatocellular Carcinoma focused on measuring Hepatocellular carcinoma, Arginine, Arginine deiminase, ADI-PEG 20

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University of Alabama
  • Southern California Research Center
  • Catherine Frenette
  • Stanford University
  • University of California at San Diego Moores Cancer Center
  • Pacific Medical Center
  • Piedmont Research Institute
  • University of Hawaii
  • University of Maryland Greenbaum Cancer Center
  • Johns Hopkins University Hospital
  • Wayne State University School of Medicine, Dept Oncology
  • University of Minnesota Cancer Center
  • Nebraska Hem-Onc
  • Memorial Sloan-Kettering Cancer Center
  • University of Oregon
  • Drexel University
  • University of Pennsylvania Abramson Cancer Center
  • UPMC Cancer Centers
  • UT Southwestern
  • Michael E. DeBakey VA Medical Center
  • University of Washington
  • A ward of Oncology-287 Changhuai Rd
  • Oncology, No. 678, Furong Rd
  • The First Hospital of Medical University Of Anhui
  • 5th Fl, Inpatient Bldg, No. 8,
  • No. 156 North Road of West Second Ring
  • 15th Floor, In-patient Building (East), No. 651 Dongfeng East Road
  • 5th Fl, Inpatient Bldg, No. 71, Heti Rd
  • 3rd Floor, Medicine Building, No. 150 Haping Rd
  • Oncology, 185 Road Juqian Street
  • The Chinese people's liberation army 81 hospital
  • 5th Floor, Medical Building, No. 1018 Huguang Rd
  • No. 193, Lianhe Rd, Shahekou Dist.
  • No. 596, Xinsi Rd., Baqiao Dist.
  • Floor 7, 3rd Inpatient Building No. 37, Guoxue Xiang
  • 13th Floor, Internal Medicine Building, No. 29 Gaotanyan Main St.
  • Bldg No. 5, 3rd Floor, Dongan Rd
  • Istituto Tumori "Giovanni Paolo II"
  • Policlinico S. Orsola-Malpighi
  • Azienda Ospedaliera Niguarda Cà Granda
  • Fondazione Centro San Raffaele del Monte Tabor
  • Fondazione IRCCs "Ca Granda" Ospedale Maggiore Policlinico
  • Policlinico di Monza
  • Istituto Nazionale per lo Studio e la Cura dei Tumori
  • Azienda Ospedaliera di Padova
  • Azienda Ospedaliera San Camillo Forlanini
  • Instituto Nazionale pler le Malattie Infettive
  • Asan Medical Center
  • Korea University Anam Hospital
  • Samsung Medical Center
  • Seoul St. Mary's Hospital
  • Severance Hospital
  • CGMHCY
  • Kaohsiung Medical University Chung-Ho Memorial Hospital
  • Chang Gung Medical Foundation-Kaohsiung
  • China Medicine University Hospital
  • CMMC-LY
  • CMMC-YK
  • National Cheng Kung University Hospital
  • Northern Taiwan University Hospital
  • Mackay Memorial Hospital-Taipei Branch
  • Taipei Veterans General Hospital
  • Chang Gung Medical Foundation-Linkou
  • Clatterbridge Cancer Center
  • University Hospitals Birmingham NHS Foundation Trust
  • Hammersmith Hospital
  • King's College Hospital
  • Royal Free Hospital
  • St. Bartholomew's Hospital
  • The Royal Marsden Hospital
  • Christie NHS Trust
  • Nottingham University Hospital
  • Royal Marsden

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

ADI-PEG 20

Placebo

Arm Description

Arginine deiminase formulated with polyethylene glycol.

an inert treatment with no therapeutic value.

Outcomes

Primary Outcome Measures

Overall survival
Overall survival - until death or study closure.

Secondary Outcome Measures

Safety and tolerability - number of participants with adverse events.
In addition to safety and tolerability, progression free survival, response rate using RECIST 1.1 and time to tumor progression will be assessed.

Full Information

First Posted
January 25, 2011
Last Updated
August 27, 2019
Sponsor
Polaris Group
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1. Study Identification

Unique Protocol Identification Number
NCT01287585
Brief Title
Ph 3 ADI-PEG 20 Versus Placebo in Subjects With Advanced Hepatocellular Carcinoma Who Have Failed Prior Systemic Therapy
Acronym
ADI-PEG 20
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 Type
Interventional

2. Study Status

Record Verification Date
August 2016
Overall Recruitment Status
Completed
Study Start Date
July 2011 (undefined)
Primary Completion Date
July 2015 (Actual)
Study Completion Date
July 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Polaris Group

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatocellular Carcinoma
Keywords
Hepatocellular carcinoma, Arginine, Arginine deiminase, ADI-PEG 20

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
636 (Actual)

8. Arms, Groups, and Interventions

Arm Title
ADI-PEG 20
Arm Type
Experimental
Arm Description
Arginine deiminase formulated with polyethylene glycol.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
an inert treatment with no therapeutic value.
Intervention Type
Drug
Intervention Name(s)
ADI-PEG 20 (arginine deiminase formulated with polyethylene glycol)
Intervention Description
18 mg/m2, weekly, intramuscular, until disease progression or toxicity.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
weekly, intramuscular, until disease progression or toxicity.
Intervention Type
Other
Intervention Name(s)
Best Supportive Care
Intervention Description
treatment of disease-related symptoms throughout the study.
Primary Outcome Measure Information:
Title
Overall survival
Description
Overall survival - until death or study closure.
Time Frame
18 months
Secondary Outcome Measure Information:
Title
Safety and tolerability - number of participants with adverse events.
Description
In addition to safety and tolerability, progression free survival, response rate using RECIST 1.1 and time to tumor progression will be assessed.
Time Frame
18 months - at anticipated end of study.

10. Eligibility

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

12. IPD Sharing Statement

Citations:
PubMed Identifier
29659672
Citation
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.
Results Reference
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Learn more about this trial

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

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