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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Polaris Group
ClinicalTrials.gov Identifier:
NCT01287585
First received: January 25, 2011
Last updated: February 4, 2015
Last verified: February 2015
  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: December 2015
Estimated Primary Completion Date: August 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

  Hide Study Locations
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
Johns Hopkins University Hospital
Baltimore, Maryland, United States
University of Maryland Greenbaum Cancer Center
Baltimore, Maryland, United States, 21201
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
University of Pennsylvania Abramson Cancer Center
Philadelphia, Pennsylvania, United States
Drexel University
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
China
13th Floor, Internal Medicine Building, No. 29 Gaotanyan Main St.
ChongQing, China, 400038
Bldg No. 5, 3rd Floor, Dongan Rd
Shanghai, China
Italy
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
Severance Hospital
Seoul, 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
Taiwan
CGMHCY
ChiaYi, Taiwan
Kaohsiung Medical University Chung-Ho Memorial Hospital
Kaohsiung City, Taiwan
Chang Gung Medical Foundation-Kaohsiung
Kaohsiung County, Taiwan
China Medicine University Hopsital
Taichung, Taiwan, 40447
National Cheng Kung University Hospital
Tainan, Taiwan
CMMC-YK
Tainan City, Taiwan
CMMC-LY
Tainan City, Taiwan
Taipei Veterans General Hospital
Taipei, Taiwan
Mackay Memorial Hospital-Taipei Branch
Taipei, Taiwan
Northern Taiwan University Hospital
Taipei City, 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
The Royal Marsden Hospital
London, United Kingdom
Hammersmith Hospital
London, United Kingdom
Royal Free Hospital
London, United Kingdom
St. Bartholomew's Hospital
London, United Kingdom
King's College 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
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: February 4, 2015
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, Hepatocellular
Adenocarcinoma
Carcinoma
Digestive System Diseases
Digestive System Neoplasms
Liver Diseases
Liver Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on March 25, 2015