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

NCT ID: NCT01287585

Last Updated: 2019-09-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

636 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-07-31

Study Completion Date

2015-07-31

Brief Summary

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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

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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).

Conditions

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Hepatocellular Carcinoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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ADI-PEG 20

Arginine deiminase formulated with polyethylene glycol.

Group Type EXPERIMENTAL

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

Intervention Type DRUG

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

Best Supportive Care

Intervention Type OTHER

treatment of disease-related symptoms throughout the study.

Placebo

an inert treatment with no therapeutic value.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

weekly, intramuscular, until disease progression or toxicity.

Best Supportive Care

Intervention Type OTHER

treatment of disease-related symptoms throughout the study.

Interventions

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

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

Intervention Type DRUG

Placebo

weekly, intramuscular, until disease progression or toxicity.

Intervention Type DRUG

Best Supportive Care

treatment of disease-related symptoms throughout the study.

Intervention Type OTHER

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Polaris Group

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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John S Bomalaski, M.D.

Role: STUDY_DIRECTOR

Polaris Group

Locations

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University of Alabama

Birmingham, Alabama, United States

Site Status

Southern California Research Center

Coronado, California, United States

Site Status

Catherine Frenette

La Jolla, California, United States

Site Status

Stanford University

Palo Alto, California, United States

Site Status

University of California at San Diego Moores Cancer Center

San Diego, California, United States

Site Status

Pacific Medical Center

San Francisco, California, United States

Site Status

Piedmont Research Institute

Atlanta, Georgia, United States

Site Status

University of Hawaii

Honolulu, Hawaii, United States

Site Status

University of Maryland Greenbaum Cancer Center

Baltimore, Maryland, United States

Site Status

Johns Hopkins University Hospital

Baltimore, Maryland, United States

Site Status

Wayne State University School of Medicine, Dept Oncology

Detroit, Michigan, United States

Site Status

University of Minnesota Cancer Center

Minneapolis, Minnesota, United States

Site Status

Nebraska Hem-Onc

Lincoln, Nebraska, United States

Site Status

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Site Status

University of Oregon

Portland, Oregon, United States

Site Status

Drexel University

Philadelphia, Pennsylvania, United States

Site Status

University of Pennsylvania Abramson Cancer Center

Philadelphia, Pennsylvania, United States

Site Status

UPMC Cancer Centers

Pittsburgh, Pennsylvania, United States

Site Status

UT Southwestern

Dallas, Texas, United States

Site Status

Michael E. DeBakey VA Medical Center

Houston, Texas, United States

Site Status

University of Washington

Seattle, Washington, United States

Site Status

A ward of Oncology-287 Changhuai Rd

Bengbu, Anhui, China

Site Status

Oncology, No. 678, Furong Rd

Hefei, Anhui, China

Site Status

The First Hospital of Medical University Of Anhui

Hefei, Anhui, China

Site Status

5th Fl, Inpatient Bldg, No. 8,

Fengtai Distrcit, Beijing Municipality, China

Site Status

No. 156 North Road of West Second Ring

Gulou District, Fujian, China

Site Status

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

Guangzhou, Guangdong, China

Site Status

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

Qingxiu Disttrict, Guangxi, China

Site Status

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

Harbin, Heilongjiang, China

Site Status

Oncology, 185 Road Juqian Street

Changzhou, Jiangsu, China

Site Status

The Chinese people's liberation army 81 hospital

Nanjing, Jiangsu, China

Site Status

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

Changchun, Jilin, China

Site Status

No. 193, Lianhe Rd, Shahekou Dist.

Dalian, Liaoning, China

Site Status

No. 596, Xinsi Rd., Baqiao Dist.

Xi'an, Shaanxi, China

Site Status

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

Chengdu, Sichuan, China

Site Status

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

Chongqing, , China

Site Status

Bldg No. 5, 3rd Floor, Dongan Rd

Shanghai, , China

Site Status

Istituto Tumori "Giovanni Paolo II"

Bari, , Italy

Site Status

Policlinico S. Orsola-Malpighi

Bologna, , Italy

Site Status

Azienda Ospedaliera Niguarda Cà Granda

Milan, , Italy

Site Status

Fondazione Centro San Raffaele del Monte Tabor

Milan, , Italy

Site Status

Fondazione IRCCs "Ca Granda" Ospedale Maggiore Policlinico

Milan, , Italy

Site Status

Policlinico di Monza

Monza, , Italy

Site Status

Istituto Nazionale per lo Studio e la Cura dei Tumori

Naples, , Italy

Site Status

Azienda Ospedaliera di Padova

Padua, , Italy

Site Status

Azienda Ospedaliera San Camillo Forlanini

Roma, , Italy

Site Status

Instituto Nazionale pler le Malattie Infettive

Rome, , Italy

Site Status

Asan Medical Center

Seoul, , South Korea

Site Status

Korea University Anam Hospital

Seoul, , South Korea

Site Status

Samsung Medical Center

Seoul, , South Korea

Site Status

Seoul St. Mary's Hospital

Seoul, , South Korea

Site Status

Severance Hospital

Seoul, , South Korea

Site Status

CGMHCY

Chiayi City, , Taiwan

Site Status

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, , Taiwan

Site Status

Chang Gung Medical Foundation-Kaohsiung

Kaohsiung County, , Taiwan

Site Status

China Medicine University Hospital

Taichung, , Taiwan

Site Status

CMMC-LY

Tainan City, , Taiwan

Site Status

CMMC-YK

Tainan City, , Taiwan

Site Status

National Cheng Kung University Hospital

Tainan City, , Taiwan

Site Status

Mackay Memorial Hospital-Taipei Branch

Taipei, , Taiwan

Site Status

Northern Taiwan University Hospital

Taipei, , Taiwan

Site Status

Taipei Veterans General Hospital

Taipei, , Taiwan

Site Status

Chang Gung Medical Foundation-Linkou

Taoyuan, , Taiwan

Site Status

Clatterbridge Cancer Center

Bebington, , United Kingdom

Site Status

University Hospitals Birmingham NHS Foundation Trust

Birmingham, , United Kingdom

Site Status

Hammersmith Hospital

London, , United Kingdom

Site Status

King's College Hospital

London, , United Kingdom

Site Status

Royal Free Hospital

London, , United Kingdom

Site Status

St. Bartholomew's Hospital

London, , United Kingdom

Site Status

The Royal Marsden Hospital

London, , United Kingdom

Site Status

Christie NHS Trust

Manchester, , United Kingdom

Site Status

Nottingham University Hospital

Nottingham, , United Kingdom

Site Status

Royal Marsden

Sutton, , United Kingdom

Site Status

Countries

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United States China Italy South Korea Taiwan United Kingdom

References

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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.

Reference Type BACKGROUND
PMID: 29659672 (View on PubMed)

Other Identifiers

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POLARIS2009-001

Identifier Type: -

Identifier Source: org_study_id

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