Clinical trial NCT01287585: Ph 3 ADI-PEG 20 Versus Placebo in Subjects With Advanced Hepatocellular Carcinoma Who Have Failed Prior Systemic Therapy
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hepatocellular Carcinoma
Keywords: Hepatocellular carcinoma
Arginine
Arginine deiminase
ADI-PEG 20
Lead sponsor: Polaris Group
Sponsor class: INDUSTRY
First posted: 2011-02-01
Enrollment: 636
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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 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.

Primary outcomes:
measure: Overall survival
timeFrame: 18 months
Secondary outcomes:
measure: Safety and tolerability - number of participants with adverse events.
timeFrame: 18 months - at anticipated end of study.
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: Coronado
country: United States
facility: Southern California Research Center
state: California
city: La Jolla
country: United States
facility: Catherine Frenette
state: California
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: San Diego
country: United States
facility: University of California at San Diego Moores Cancer Center
state: California
city: San Francisco
country: United States
facility: Pacific Medical Center
state: California
city: Atlanta
country: United States
facility: Piedmont Research Institute
state: Georgia
city: Honolulu
country: United States
facility: University of Hawaii
state: Hawaii
city: Baltimore
country: United States
facility: University of Maryland Greenbaum Cancer Center
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins University Hospital
state: Maryland
city: Detroit
country: United States
facility: Wayne State University School of Medicine, Dept Oncology
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota Cancer Center
state: Minnesota
city: Lincoln
country: United States
facility: Nebraska Hem-Onc
state: Nebraska
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Portland
country: United States
facility: University of Oregon
state: Oregon
city: Philadelphia
country: United States
facility: Drexel University
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania Abramson Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Cancer Centers
state: Pennsylvania
city: Dallas
country: United States
facility: UT Southwestern
state: Texas
city: Houston
country: United States
facility: Michael E. DeBakey VA Medical Center
state: Texas
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Bengbu
country: China
facility: A ward of Oncology-287 Changhuai Rd
state: Anhui
city: Hefei
country: China
facility: Oncology, No. 678, Furong Rd
state: Anhui
city: Hefei
country: China
facility: The First Hospital of Medical University Of Anhui
state: Anhui
city: Fengtai Distrcit
country: China
facility: 5th Fl, Inpatient Bldg, No. 8,
state: Beijing
city: Gulou District
country: China
facility: No. 156 North Road of West Second Ring
state: Fujian
city: Guangzhou
country: China
facility: 15th Floor, In-patient Building (East), No. 651 Dongfeng East Road
state: Guangdong
city: Qingxiu Disttrict
country: China
facility: 5th Fl, Inpatient Bldg, No. 71, Heti Rd
state: Guangxi
city: Harbin
country: China
facility: 3rd Floor, Medicine Building, No. 150 Haping Rd
state: Heilongjiang
city: Changzhou
country: China
facility: Oncology, 185 Road Juqian Street
state: Jiangsu
city: Nanjing
country: China
facility: The Chinese people's liberation army 81 hospital
state: Jiangsu
city: Changchun
country: China
facility: 5th Floor, Medical Building, No. 1018 Huguang Rd
state: Jilin
city: Dalian
country: China
facility: No. 193, Lianhe Rd, Shahekou Dist.
state: Liaoning
city: Xi'an
country: China
facility: No. 596, Xinsi Rd., Baqiao Dist.
state: Shaanxi
city: Cheng Du
country: China
facility: Floor 7, 3rd Inpatient Building No. 37, Guoxue Xiang
state: Sichuan
city: ChongQing
country: China
facility: 13th Floor, Internal Medicine Building, No. 29 Gaotanyan Main St.
city: Shanghai
country: China
facility: Bldg No. 5, 3rd Floor, Dongan Rd
city: Bari
country: Italy
facility: Istituto Tumori "Giovanni Paolo II"
city: Bologna
country: Italy
facility: Policlinico S. Orsola-Malpighi
city: Milan
country: Italy
facility: Azienda Ospedaliera Niguarda Cà Granda
city: Milan
country: Italy
facility: Fondazione Centro San Raffaele del Monte Tabor
city: Milan
country: Italy
facility: Fondazione IRCCs "Ca Granda" Ospedale Maggiore Policlinico
city: Monza
country: Italy
facility: Policlinico di Monza
city: Naples
country: Italy
facility: Istituto Nazionale per lo Studio e la Cura dei Tumori
city: Padova
country: Italy
facility: Azienda Ospedaliera di Padova
city: Roma
country: Italy
facility: Azienda Ospedaliera San Camillo Forlanini
city: Rome
country: Italy
facility: Instituto Nazionale pler le Malattie Infettive
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul St. Mary's Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: ChiaYi
country: Taiwan
facility: CGMHCY
city: Kaohsiung City
country: Taiwan
facility: Kaohsiung Medical University Chung-Ho Memorial Hospital
city: Kaohsiung County
country: Taiwan
facility: Chang Gung Medical Foundation-Kaohsiung
city: Taichung
country: Taiwan
facility: China Medicine University Hospital
city: Tainan City
country: Taiwan
facility: CMMC-LY
city: Tainan City
country: Taiwan
facility: CMMC-YK
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei City
country: Taiwan
facility: Northern Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Mackay Memorial Hospital-Taipei Branch
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taoyuan County
country: Taiwan
facility: Chang Gung Medical Foundation-Linkou
city: Bebington
country: United Kingdom
facility: Clatterbridge Cancer Center
city: Birmingham
country: United Kingdom
facility: University Hospitals Birmingham NHS Foundation Trust
city: London
country: United Kingdom
facility: Hammersmith Hospital
city: London
country: United Kingdom
facility: King's College Hospital
city: London
country: United Kingdom
facility: Royal Free Hospital
city: London
country: United Kingdom
facility: St. Bartholomew's Hospital
city: London
country: United Kingdom
facility: The Royal Marsden Hospital
city: Manchester
country: United Kingdom
facility: Christie NHS Trust
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospital
city: Sutton
country: United Kingdom
facility: Royal Marsden
Study officials:
affiliation: Polaris Group
name: John S Bomalaski, M.D.
role: STUDY_DIRECTOR
References:
citation: 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.