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

August 27, 2019 updated by: Polaris Group

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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).

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
636

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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.
Other: Best Supportive Care
treatment of disease-related symptoms throughout the study.
Placebo Comparator: Placebo
an inert treatment with no therapeutic value.
Other: Best Supportive Care
treatment of disease-related symptoms throughout the study.
Drug: Placebo
weekly, intramuscular, until disease progression or toxicity.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: 18 months
Overall survival - until death or study closure.
18 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Safety and tolerability - number of participants with adverse events.
Time Frame: 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.
18 months - at anticipated end of study.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Polaris Group

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: John S Bomalaski, M.D., Polaris Group

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 1, 2011

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 1, 2015

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 1, 2015

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 25, 2011

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 31, 2011

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 1, 2011

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 6, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 27, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • POLARIS2009-001

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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