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

Hepatocellular Carcinoma Clinical Trial

— ADI-PEG 20  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01287585
• Other study ID #: POLARIS2009-001
• Status: Completed
• Phase: Phase 3
• Start date: July 2011
• Est. completion date: July 2015

Study information

• Verified date: August 2016
• Source: Polaris Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. Thus the hypothesis is that by restricting arginine with ADI-PEG 20, the hepatocellular carcinoma cells will starve and die.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 636
• Est. completion date: July 2015
• Est. primary completion date: July 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma

Intervention

Drug:
• ADI-PEG 20 (arginine deiminase formulated with polyethylene glycol)
18 mg/m2, weekly, intramuscular, until disease progression or toxicity.
• Placebo
weekly, intramuscular, until disease progression or toxicity.

Other:
• Best Supportive Care
treatment of disease-related symptoms throughout the study.

Locations

Country	Name	City	State
China	A ward of Oncology-287 Changhuai Rd	Bengbu	Anhui
China	5th Floor, Medical Building, No. 1018 Huguang Rd	Changchun	Jilin
China	Oncology, 185 Road Juqian Street	Changzhou	Jiangsu
China	Floor 7, 3rd Inpatient Building No. 37, Guoxue Xiang	Cheng Du	Sichuan
China	13th Floor, Internal Medicine Building, No. 29 Gaotanyan Main St.	ChongQing
China	No. 193, Lianhe Rd, Shahekou Dist.	Dalian	Liaoning
China	5th Fl, Inpatient Bldg, No. 8,	Fengtai Distrcit	Beijing
China	15th Floor, In-patient Building (East), No. 651 Dongfeng East Road	Guangzhou	Guangdong
China	No. 156 North Road of West Second Ring	Gulou District	Fujian
China	3rd Floor, Medicine Building, No. 150 Haping Rd	Harbin	Heilongjiang
China	Oncology, No. 678, Furong Rd	Hefei	Anhui
China	The First Hospital of Medical University Of Anhui	Hefei	Anhui
China	The Chinese people's liberation army 81 hospital	Nanjing	Jiangsu
China	5th Fl, Inpatient Bldg, No. 71, Heti Rd	Qingxiu Disttrict	Guangxi
China	Bldg No. 5, 3rd Floor, Dongan Rd	Shanghai
China	No. 596, Xinsi Rd., Baqiao Dist.	Xi'an	Shaanxi
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
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	Severance Hospital	Seoul
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 Hospital	Taichung
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	CMMC-LY	Tainan City
Taiwan	CMMC-YK	Tainan City
Taiwan	Mackay Memorial Hospital-Taipei Branch	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei
Taiwan	Northern Taiwan University Hospital	Taipei City
Taiwan	Chang Gung Medical Foundation-Linkou	Taoyuan County
United Kingdom	Clatterbridge Cancer Center	Bebington
United Kingdom	University Hospitals Birmingham NHS Foundation Trust	Birmingham
United Kingdom	Hammersmith Hospital	London
United Kingdom	King's College Hospital	London
United Kingdom	Royal Free Hospital	London
United Kingdom	St. Bartholomew's Hospital	London
United Kingdom	The Royal Marsden Hospital	London
United Kingdom	Christie NHS Trust	Manchester
United Kingdom	Nottingham University Hospital	Nottingham
United Kingdom	Royal Marsden	Sutton
United States	Piedmont Research Institute	Atlanta	Georgia
United States	Johns Hopkins University Hospital	Baltimore	Maryland
United States	University of Maryland Greenbaum Cancer Center	Baltimore	Maryland
United States	University of Alabama	Birmingham	Alabama
United States	Southern California Research Center	Coronado	California
United States	UT Southwestern	Dallas	Texas
United States	Wayne State University School of Medicine, Dept Oncology	Detroit	Michigan
United States	University of Hawaii	Honolulu	Hawaii
United States	Michael E. DeBakey VA Medical Center	Houston	Texas
United States	Catherine Frenette	La Jolla	California
United States	Nebraska Hem-Onc	Lincoln	Nebraska
United States	University of Minnesota Cancer Center	Minneapolis	Minnesota
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Stanford University	Palo Alto	California
United States	Drexel University	Philadelphia	Pennsylvania
United States	University of Pennsylvania Abramson Cancer Center	Philadelphia	Pennsylvania
United States	UPMC Cancer Centers	Pittsburgh	Pennsylvania
United States	University of Oregon	Portland	Oregon
United States	University of California at San Diego Moores Cancer Center	San Diego	California
United States	Pacific Medical Center	San Francisco	California
United States	University of Washington	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Polaris Group

Countries where clinical trial is conducted

United States,  China,  Italy,  Korea, Republic of,  Taiwan,  United Kingdom, 

References & Publications (1)

Abou-Alfa GK, Qin S, Ryoo BY, Lu SN, Yen C-J, Feng YH, Lim HY, Izzo F, Colombo M, Sarker D, Bolondi L, Vaccaro GM, Harris WP, Chen Z, Hubner R, Meyer T, Bomalaski JS, Lin CC, Chao Y, Chen LZ. 2016. Phase III randomized study of second line ADI-peg 20 (A) plus best supportive care versus placebo (P) plus best supportive care in patients (pts) with advanced hepatocellular carcinoma (HCC). J Clin Oncol 34, 2016 (suppl; abstr 4017).

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival	Overall survival - until death or study closure.	18 months
Secondary	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.	18 months - at anticipated end of study.

External Links

•   ACSO Abstract