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Hepatocellular CarcinomaPhase 3ADI-PEG 20NCT01287585

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

A Phase 3 study testing ADI-PEG 20 (arginine deiminase formulated with polyethylene glycol) in people with Hepatocellular Carcinoma, run by Polaris Group at 73 sites in 6 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Hepatocellular Carcinoma
What is being tested?
ADI-PEG 20 (arginine deiminase formulated with polyethylene glycol)
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
636 participants
Where
73 sitesin 6 countries
Study dates
Jul 2011to Jul 2015
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 17Show fewer
  • 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.

Trial locations and contacts

73 sites in 6 countries.

73 sites in 6 countries

United States21 sites

  • Piedmont Research Institute

    Atlanta, Georgia

  • University of Maryland Greenbaum Cancer Center

    Baltimore, Maryland, 21201

  • Johns Hopkins University Hospital

    Baltimore, Maryland

  • University of Alabama

    Birmingham, Alabama

  • Southern California Research Center

    Coronado, California, 92118

  • UT Southwestern

    Dallas, Texas

  • Wayne State University School of Medicine, Dept Oncology

    Detroit, Michigan, 48201

  • University of Hawaii

    Honolulu, Hawaii

  • Michael E. DeBakey VA Medical Center

    Houston, Texas

  • Catherine Frenette

    La Jolla, California, 92037

  • Nebraska Hem-Onc

    Lincoln, Nebraska

  • University of Minnesota Cancer Center

    Minneapolis, Minnesota

  • Memorial Sloan-Kettering Cancer Center

    New York, New York, 10065

  • Stanford University

    Palo Alto, California

  • Drexel University

    Philadelphia, Pennsylvania

  • University of Pennsylvania Abramson Cancer Center

    Philadelphia, Pennsylvania

  • UPMC Cancer Centers

    Pittsburgh, Pennsylvania

  • University of Oregon

    Portland, Oregon

  • University of California at San Diego Moores Cancer Center

    San Diego, California

  • Pacific Medical Center

    San Francisco, California

  • University of Washington

    Seattle, Washington

Other trials in United States

China16 sites

  • A ward of Oncology-287 Changhuai Rd

    Bengbu, Anhui, 233000

  • 5th Floor, Medical Building, No. 1018 Huguang Rd

    Changchun, Jilin, 116011

  • Oncology, 185 Road Juqian Street

    Changzhou, Jiangsu, 213003

  • Floor 7, 3rd Inpatient Building No. 37, Guoxue Xiang

    Chengdu, Sichuan, 610041

  • 13th Floor, Internal Medicine Building, No. 29 Gaotanyan Main St.

    Chongqing, 400038

  • No. 193, Lianhe Rd, Shahekou Dist.

    Dalian, Liaoning, 116011

  • 5th Fl, Inpatient Bldg, No. 8,

    Fengtai Distrcit, Beijing Municipality, 100071

  • 15th Floor, In-patient Building (East), No. 651 Dongfeng East Road

    Guangzhou, Guangdong, 510060

  • No. 156 North Road of West Second Ring

    Gulou District, Fujian, 350025

  • 3rd Floor, Medicine Building, No. 150 Haping Rd

    Harbin, Heilongjiang, 150040

  • Oncology, No. 678, Furong Rd

    Hefei, Anhui, 230601

  • The First Hospital of Medical University Of Anhui

    Hefei, Anhui

  • The Chinese people's liberation army 81 hospital

    Nanjing, Jiangsu

  • 5th Fl, Inpatient Bldg, No. 71, Heti Rd

    Qingxiu Disttrict, Guangxi, 530021

  • Bldg No. 5, 3rd Floor, Dongan Rd

    Shanghai

  • No. 596, Xinsi Rd., Baqiao Dist.

    Xi'an, Shaanxi, 710038

Other trials in China

Taiwan11 sites

  • CGMHCY

    Chiayi City

  • Kaohsiung Medical University Chung-Ho Memorial Hospital

    Kaohsiung City

  • Chang Gung Medical Foundation-Kaohsiung

    Kaohsiung County

  • China Medicine University Hospital

    Taichung, 40447

  • CMMC-LY

    Tainan

  • CMMC-YK

    Tainan

  • National Cheng Kung University Hospital

    Tainan

  • Mackay Memorial Hospital-Taipei Branch

    Taipei

  • Northern Taiwan University Hospital

    Taipei

  • Taipei Veterans General Hospital

    Taipei

  • Chang Gung Medical Foundation-Linkou

    Taoyuan County

Other trials in Taiwan

Italy10 sites

  • Istituto Tumori "Giovanni Paolo II"

    Bari

  • Policlinico S. Orsola-Malpighi

    Bologna

  • Azienda Ospedaliera Niguarda Cà Granda

    Milan

  • Fondazione Centro San Raffaele del Monte Tabor

    Milan

  • Fondazione IRCCs "Ca Granda" Ospedale Maggiore Policlinico

    Milan

  • Policlinico di Monza

    Monza

  • Istituto Nazionale per lo Studio e la Cura dei Tumori

    Naples

  • Azienda Ospedaliera di Padova

    Padova

  • Azienda Ospedaliera San Camillo Forlanini

    Roma

  • Instituto Nazionale pler le Malattie Infettive

    Rome

Other trials in Italy

United Kingdom10 sites

  • Clatterbridge Cancer Center

    Bebington

  • University Hospitals Birmingham NHS Foundation Trust

    Birmingham

  • Hammersmith Hospital

    London

  • King's College Hospital

    London

  • Royal Free Hospital

    London

  • St. Bartholomew's Hospital

    London

  • The Royal Marsden Hospital

    London

  • Christie NHS Trust

    Manchester

  • Nottingham University Hospital

    Nottingham

  • Royal Marsden

    Sutton

Other trials in United Kingdom

South Korea5 sites

  • Asan Medical Center

    Seoul

  • Korea University Anam Hospital

    Seoul

  • Samsung Medical Center

    Seoul

  • Seoul St. Mary's Hospital

    Seoul

  • Severance Hospital

    Seoul

Other trials in South Korea

About this study

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

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.

Read the 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).

Being tested
ADI-PEG 20 (arginine deiminase formulated with polyethylene glycol), Placebo, Best Supportive Care
Keywords
Hepatocellular carcinoma, Arginine, Arginine deiminase, ADI-PEG 20
Medical subject headings
Carcinoma, Hepatocellular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ADI-PEG 20 (arginine deiminase formulated with polyethylene glycol)Drug

    18 mg/m2, weekly, intramuscular, until disease progression or toxicity.

  • PlaceboDrug

    weekly, intramuscular, until disease progression or toxicity.

  • Best Supportive CareOther

    treatment of disease-related symptoms throughout the study.

Study groups in NCT01287585
Study groupRoleWhat they receive
ADI-PEG 20ExperimentalArginine deiminase formulated with polyethylene glycol.
Receives: Drug: ADI-PEG 20 (arginine deiminase formulated with polyethylene glycol); Other: Best Supportive Care
PlaceboPlacebo comparatoran inert treatment with no therapeutic value.
Receives: Drug: Placebo; Other: Best Supportive Care

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall survival

    Overall survival - until death or study closure.

    Measured: 18 months

Secondary outcomes (1)

  1. 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.

    Measured: 18 months - at anticipated end of study.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Feb 2011 (estimated)
  2. Study startJul 2011
  3. Primary completionJul 2015
  4. Study completionJul 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
636 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01287585
Sponsor's protocol ID
POLARIS2009-001
Acronym
ADI-PEG 20
Status last verified
Aug 2016
First submitted
25 Jan 2011
Last updated
6 Sep 2019
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 29659672

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing ADI-PEG 20 (arginine deiminase formulated with polyethylene glycol) in people with Hepatocellular Carcinoma, run by Polaris Group at 73 sites in 6 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 73 sites in United States, China, Taiwan, Italy, United Kingdom and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall survival (time frame: 18 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01287585, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Sep 2019.

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