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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Polaris Group
Sponsor:
Information provided by (Responsible Party):
Polaris Group
ClinicalTrials.gov Identifier:
NCT01287585
First received: January 25, 2011
Last updated: May 8, 2014
Last verified: May 2014
  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: March 2016
Estimated Primary Completion Date: December 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

Contacts
Contact: John S Bomalaski, M.D. 858-452-6688 ext 114 jbomalaski@polarispharma.com

  Hide Study Locations
Locations
United States, Alabama
University of Alabama Recruiting
Birmingham, Alabama, United States
Principal Investigator: Kelly Godby, MD         
United States, California
Southern California Research Center Terminated
Coronado, California, United States, 92118
Catherine Frenette Terminated
La Jolla, California, United States, 92037
Stanford University Recruiting
Palo Alto, California, United States
Contact: David Fisher, MD         
Principal Investigator: Cheryl Cho-Phan, MD         
University of California at San Diego Moores Cancer Center Recruiting
San Diego, California, United States
Contact: Robert Gish, MD         
Principal Investigator: Robert Gish, MD         
Pacific Medical Center Recruiting
San Francisco, California, United States
Principal Investigator: Ari Baron, MD         
United States, Georgia
Piedmont Research Institute Recruiting
Atlanta, Georgia, United States
Contact: Charles Henderson, MD         
Contact: Michelle Humphreys         
Principal Investigator: Charles Henderson, MD         
United States, Hawaii
University of Hawaii Recruiting
Honolulu, Hawaii, United States
Contact: Jonathan Cho, MD         
Contact: Debbie Bielecki         
Principal Investigator: Jonathan Cho, MD         
United States, Maryland
University of Maryland Greenbaum Cancer Center Recruiting
Baltimore, Maryland, United States, 21201
Contact: Margit Naomi Horiba, MD         
Principal Investigator: Margit Naomi Horiba, MD         
Johns Hopkins University Hospital Recruiting
Baltimore, Maryland, United States
Contact: David Cosgrove, MD         
Principal Investigator: David Cosgrove, MD         
United States, Michigan
Wayne State University School of Medicine, Dept Oncology Recruiting
Detroit, Michigan, United States, 48201
Contact: Hemchandra Mahaseth, MD         
Principal Investigator: Hemchandra Mahaseth, MD         
United States, Minnesota
University of Minnesota Cancer Center Recruiting
Minneapolis, Minnesota, United States
Contact: Edward Greeno, MD         
Contact: Carrie McCann         
Principal Investigator: Edward Greeno, MD         
United States, Nebraska
Nebraska Hem-Onc Recruiting
Lincoln, Nebraska, United States
Contact: Eric Avery, MD         
Principal Investigator: Eric Avery, MD         
United States, New York
Memorial Sloan-Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Ghassan Abou-Alfa, MD         
Principal Investigator: Ghassan Abou-Alfa, MD         
United States, Oregon
University of Oregon Recruiting
Portland, Oregon, United States
Contact: Gina Vaccaro, MD         
Principal Investigator: Gina Vaccaro, MD         
United States, Pennsylvania
University of Pennsylvania Abramson Cancer Center Recruiting
Philadelphia, Pennsylvania, United States
Contact: Teitelbaum, MD         
Principal Investigator: Ursina Teitelbaum, MD         
Drexel University Recruiting
Philadelphia, Pennsylvania, United States
Principal Investigator: Gary Xiao, MD         
UPMC Cancer Centers Recruiting
Pittsburgh, Pennsylvania, United States
Contact: Weijing Sun, MD         
Principal Investigator: Weijing Sun, MD         
United States, Texas
UT Southwestern Active, not recruiting
Dallas, Texas, United States
Michael E. DeBakey VA Medical Center Recruiting
Houston, Texas, United States
Contact: Teresa Hayes, MD         
Principal Investigator: Teresa Hayes, MD         
United States, Washington
University of Washington Recruiting
Seattle, Washington, United States
Principal Investigator: William Harris, MD         
China, Anhui
A ward of Oncology-287 Changhuai Rd Recruiting
Bengbu, Anhui, China, 233000
Contact: Brooke Pointer    858-452-6688 ext 110    bpointer@polarispharma.com   
Principal Investigator: Qiong Wu, MD         
Oncology, No. 678, Furong Rd Recruiting
Hefei, Anhui, China, 230601
Contact: Brooke Pointer    858-452-6688 ext 110    bpointer@polarispharma.com   
Principal Investigator: Zhendong Chen, MD         
The First Hospital of Medical University Of Anhui Recruiting
Hefei, Anhui, China
Contact: Kangsheng Gu, MD         
Principal Investigator: Kangsheng Gu, MD         
China, Beijing
5th Fl, Inpatient Bldg, No. 8, Recruiting
Fengtai Distrcit, Beijing, China, 100071
Contact: Brooke Pointer    858-452-6688 ext 110    bpointer@polarispharma.com   
Principal Investigator: Jianming Xu, MD         
China, Fujian
No. 156 North Road of West Second Ring Recruiting
Gulou District, Fujian, China, 350025
Contact: Brooke Pointer    858-452-6688 ext 110    bpointer@polarispharma.com   
Principal Investigator: Xuenong Ouyang, MD         
China, Guangdong
15th Floor, In-patient Building (East), No. 651 Dongfeng East Road Recruiting
Guangzhou, Guangdong, China, 510060
Contact: Brooke Pointer    858-452-6688 ext 110    bpointer@polarispharma.com   
Principal Investigator: Minshan Chen, MD         
China, Guangxi
5th Fl, Inpatient Bldg, No. 71, Heti Rd Recruiting
Qingxiu Disttrict, Guangxi, China, 530021
Contact: Brooke Pointer    858-452-6688 ext 110    bpointer@polarispharma.com   
Principal Investigator: Yongqiang Li, MD         
China, Heilongjiang
3rd Floor, Medicine Building, No. 150 Haping Rd Recruiting
Harbin, Heilongjiang, China, 150040
Contact: Brooke Pointer    858-452-6688 ext 110    bpointer@polarispharma.com   
Principal Investigator: Yuxian Bai, MD         
China, Jiangsu
Oncology, 185 Road Juqian Street Recruiting
Changzhou, Jiangsu, China, 213003
Contact: Brooke Pointer    858-452-6688 ext 110    bpointer@polarispharma.com   
Principal Investigator: Changping Wu, MD         
The Chinese people's liberation army 81 hospital Recruiting
Nanjing, Jiangsu, China
Contact: Shukui Qin, MD         
Principal Investigator: Shukui Qin, MD         
China, Jilin
5th Floor, Medical Building, No. 1018 Huguang Rd Recruiting
Changchun, Jilin, China, 116011
Contact: Brooke Pointer    858-452-6688 ext 110    bpointer@polarispharma.com   
Principal Investigator: Ying Cheng, MD         
China, Liaoning
No. 193, Lianhe Rd, Shahekou Dist. Recruiting
Dalian, Liaoning, China, 116011
Contact: Brooke Pointer    858-452-6688 ext 110    bpointer@polarispharma.com   
Principal Investigator: Jiwei Liu, MD         
China, Shaanxi
No. 596, Xinsi Rd., Baqiao Dist. Recruiting
Xi'an, Shaanxi, China, 710038
Contact: Brooke Pointer    858-452-6688 ext 110    bpointer@polarispharma.com   
Principal Investigator: Helong Zhang, MD         
China, Sichuan
Floor 7, 3rd Inpatient Building No. 37, Guoxue Xiang Recruiting
Cheng Du, Sichuan, China, 610041
Contact: Brooke Pointer    858-452-6688 ext 110    bpointer@polarispharma.com   
Principal Investigator: Cheng Yi, MD         
China
13th Floor, Internal Medicine Building, No. 29 Gaotanyan Main St. Recruiting
ChongQing, China, 400038
Contact: Brooke Pointer    858-452-6688 ext 110    bpointer@polarispharma.com   
Principal Investigator: Houjie Liang, MD         
Bldg No. 5, 3rd Floor, Dongan Rd Recruiting
Shanghai, China
Contact: Brooke Pointer    858-452-6688 ext 110    bpointer@polarispharma.com   
Principal Investigator: Zhiqiang Meng, MD         
Italy
Istituto Tumori "Giovanni Paolo II" Recruiting
Bari, Italy
Contact: Nicola Silvestris, MD         
Principal Investigator: Nicola Silvestris, MD         
Policlinico S. Orsola-Malpighi Recruiting
Bologna, Italy
Principal Investigator: Luigi Bolondi, MD         
Fondazione Centro San Raffaele del Monte Tabor Recruiting
Milan, Italy
Contact: Luca Gianni, MD         
Principal Investigator: Luca Gianni, MD         
Fondazione IRCCs "Ca Granda" Ospedale Maggiore Policlinico Recruiting
Milan, Italy
Contact: Massimo Colombo, MD         
Principal Investigator: Massimo Columbo, MD         
Azienda Ospedaliera Niguarda Cà Granda Recruiting
Milan, Italy
Principal Investigator: Claudio Zavaglia, MD         
Policlinico di Monza Completed
Monza, Italy
Istituto Nazionale per lo Studio e la Cura dei Tumori Recruiting
Naples, Italy
Contact: Francesco Izzo, MD         
Principal Investigator: Francesco Izzo, MD         
Azienda Ospedaliera di Padova Recruiting
Padova, Italy
Principal Investigator: Umberto Cillo, MD         
Azienda Ospedaliera San Camillo Forlanini Completed
Roma, Italy
Instituto Nazionale pler le Malattie Infettive Recruiting
Rome, Italy
Contact: Ubaldo Visco Comandini, MD         
Principal Investigator: Ubaldo Visco Comandini, MD         
Korea, Republic of
Seoul St. Mary's Hospital Active, not recruiting
Seoul, Korea, Republic of
Samsung Medical Center Active, not recruiting
Seoul, Korea, Republic of
Severance Hospital Active, not recruiting
Seoul, Korea, Republic of
Korea University Anam Hospital Active, not recruiting
Seoul, Korea, Republic of
Asan Medical Center Active, not recruiting
Seoul, Korea, Republic of
Taiwan
CGMHCY Active, not recruiting
ChiaYi, Taiwan
Kaohsiung Medical University Chung-Ho Memorial Hospital Active, not recruiting
Kaohsiung City, Taiwan
Chang Gung Medical Foundation-Kaohsiung Recruiting
Kaohsiung County, Taiwan
Contact: Sheng-Nan Lu, MD         
Principal Investigator: Sheng-Nan Lu, MD         
China Medicine University Hopsital Recruiting
Taichung, Taiwan, 40447
Contact: Long-Bin Jeng, MD         
Contact: Cheng-Yuan Peng, MD         
Principal Investigator: Long-Bin Jeng, MD         
National Cheng Kung University Hospital Recruiting
Tainan, Taiwan
Contact: Chia-Jui Yen, MD         
Principal Investigator: Chia-Jui Yen, MD         
CMMC-YK Recruiting
Tainan City, Taiwan
Contact: Yin-Hsun Feng, MD         
Principal Investigator: Yin-Hsun Feng, MD         
CMMC-LY Recruiting
Tainan City, Taiwan
Contact: Shang-Hung Chen, MD         
Principal Investigator: Shang-Hung Chen, MD         
Taipei Veterans General Hospital Active, not recruiting
Taipei, Taiwan
Mackay Memorial Hospital-Taipei Branch Active, not recruiting
Taipei, Taiwan
Northern Taiwan University Hospital Active, not recruiting
Taipei City, Taiwan
Chang Gung Medical Foundation-Linkou Recruiting
Taoyuan County, Taiwan
Contact: Chen-Chun Lin, MD         
Principal Investigator: Chen-Chun Lin, MD         
United Kingdom
Clatterbridge Cancer Center Recruiting
Bebington, United Kingdom
Contact: Daniel Palmer, MD         
Principal Investigator: Daniel Palmer, MD         
University Hospitals Birmingham NHS Foundation Trust Recruiting
Birmingham, United Kingdom
Contact: Yuk Ting Ma, MD         
Principal Investigator: Yuk Ting Ma, MD         
Royal Free Hospital Recruiting
London, United Kingdom
Contact: Tim Meyer, MD         
Principal Investigator: Tim Meyer, MD         
St. Bartholomew's Hospital Recruiting
London, United Kingdom
Contact: David Propper, MD         
Principal Investigator: David Propper, MD         
King's College Hospital Recruiting
London, United Kingdom
Principal Investigator: Debashis Sarker, MD         
Hammersmith Hospital Recruiting
London, United Kingdom
Contact: Halpreet Wasan, MD         
Principal Investigator: Halpreet Wasan, MD         
The Royal Marsden Hospital Completed
London, United Kingdom
Christie NHS Trust Recruiting
Manchester, United Kingdom
Contact: Richard Hubner, MD         
Principal Investigator: Richard Hubner, MD         
Nottingham University Hospital Completed
Nottingham, United Kingdom
Royal Marsden Recruiting
Sutton, United Kingdom
Principal Investigator: Ian Chau, MD         
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: May 8, 2014
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
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases

ClinicalTrials.gov processed this record on August 25, 2014