Clinical trial NCT02562755: Hepatocellular Carcinoma Study Comparing Vaccinia Virus Based Immunotherapy Plus Sorafenib vs Sorafenib Alone
Official title: A Phase 3 Randomized, Open-Label Study Comparing Pexa Vec (Vaccinia GM CSF / Thymidine Kinase-Deactivated Virus) Followed by Sorafenib Versus Sorafenib in Patients With Advanced Hepatocellular Carcinoma (HCC) Without Prior Systemic Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hepatocellular Carcinoma (HCC)
Keywords: Hepatocellular Carcinoma (HCC)
Pexastimogene Devacirepvec (Pexa-Vec)
Sorafenib
GM-CSF therapy
Thymidine Kinase-Deactivated Vaccinia Virus
Oncology
Recombinant Vaccinia Virus
Oncolytic Virus Therapy
Oncolytic virotherapy
Lead sponsor: SillaJen, Inc.
Sponsor class: INDUSTRY
First posted: 2015-09-29
Enrollment: 459
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 randomized Phase 3 study to determine whether treatment with vaccinia virus based immunotherapy (Pexa-Vec) followed by sorafenib increases survival compared to treatment with sorafenib in patients with advanced hepatocellular carcinoma who have not received prior systemic therapy.

Detailed description: This is a multi-center, randomized, open-label, Phase 3 study comparing Pexa Vec followed by sorafenib versus sorafenib in patients with advanced HCC without prior systemic therapy.

A total of 459 patients were randomly assigned to 2 treatment arms- 234 patients in the Pexa-Vec followed by sorafenib treatment group and 225 patients in the sorafenib only treatment group.

Eligibility criteria: Inclusion Criteria:

* Histological/cytological diagnosis of primary HCC
* Advanced stage HCC (Barcelona Clinic Liver Cancer \[BCLC\] Stage C or B per American Association for the Study of Liver Disease \[AASLD\] guidelines)
* At least one measurable viable tumor in the liver, ≥1 cm longest diameter (LD), using a dynamic imaging technique (arterial phase of triphasic computerized tomography \[CT\] scan, or dynamic contrast-enhanced magnetic resonance imaging \[MRI\]), and injectable under imaging-guidance (CT and/or ultrasound)
* Child-Pugh Class A
* Performance status 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale
* Adequate hematological, hepatic, and renal function:
* Additional inclusion criteria exist

Exclusion Criteria:

* Histological diagnosis of cholangiocarcinoma, hepatocholangiocarcinoma, fibrolamellar carcinoma and hepatoblastoma
* Symptomatic cardiovascular disease, including but not limited to significant coronary artery disease (e.g., requiring angioplasty or stenting) or congestive heart failure within the preceding 12 months
* Current or past history of cardiovascular disease (e.g.. past history of myocardial infarction, ischemic cardiomyopathy) unless cardiology consultation and clearance has been obtained for study participation
* History of moderate or severe ascites, bleeding esophageal varices, hepatic encephalopathy or pleural effusions related to liver insufficiency within 6 months of screening
* Bulky disease patients - tumors encompassing \>50% of the liver volume and / or inferior vena cava invasion
* Known significant immunodeficiency due to underlying illness (e.g., HIV/AIDS) and/or immune-suppressive medication including high-dose corticosteroids
* Ongoing severe inflammatory skin condition (as determined by the Investigator) requiring medical treatment
* History of severe eczema (as determined by the Investigator) requiring medical treatment
* Additional exclusion criteria exist

Primary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: From date of randomization to the date of first documented radiographic tumor progression up to 53 months
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: Scottsdale
country: United States
facility: Mayo Clinic Arizona
state: Arizona
city: Orange
country: United States
facility: UC Irvine Medical Center
state: California
city: Palo Alto
country: United States
facility: Stanford University School of Medicine
state: California
city: Gainesville
country: United States
facility: University of Florida Shands Hospital
state: Florida
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Cancer Center
state: Kansas
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: New Orleans
country: United States
facility: Tulane University Health Sciences Center
state: Louisiana
city: Baltimore
country: United States
facility: Mercy Medical Center, Inc.
state: Maryland
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Kansas City
country: United States
facility: Kansas City Research Institute
state: Missouri
city: Saint Louis
country: United States
facility: Saint Louis University
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Billings
country: United States
facility: Billings Clinic
state: Montana
city: Morristown
country: United States
facility: Morristown Medical Center
state: New Jersey
city: Paterson
country: United States
facility: St. Joseph's Hospital
state: New Jersey
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Philadelphia
country: United States
facility: Hospital of The University of Pennsylvania
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Knoxville
country: United States
facility: University of Tennessee Medical Center
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Seattle
country: United States
facility: Benaroya Research Institute at Virginia Mason Hospital
state: Washington
city: Adelaide
country: Australia
facility: Site No. 8409
city: Adelaide
country: Australia
facility: Site No. 8412
city: Brisbane
country: Australia
facility: Site No. 8403
city: Camperdown
country: Australia
facility: Site No. 8401
city: Clayton
country: Australia
facility: Site No. 8407
city: Concord
country: Australia
facility: Site No. 8406
city: Fitzroy
country: Australia
facility: Site No. 8408
city: Footscray
country: Australia
facility: Site No. 8405
city: Heidelberg
country: Australia
facility: Site No. 8414
city: Melbourne
country: Australia
facility: Site No. 8411
city: Parkville
country: Australia
facility: Site No. 8402
city: Perth
country: Australia
facility: Site No. 8415
city: Sydney
country: Australia
facility: Site No. 8413
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
city: Hamilton
country: Canada
facility: Juravinski Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Changchun
country: China
facility: Site 8829
city: Changsha
country: China
facility: Site No. 8821
city: Fuzhou
country: China
facility: Site 8811
city: Fuzhou
country: China
facility: Site 8820
city: Guangdong
country: China
facility: Site No.8816
city: Guangzhou
country: China
facility: Site 8827
city: Guangzhou
country: China
facility: Site No.8828
city: Hangzhou
country: China
facility: Site 8832
city: Harbin
country: China
facility: Site No. 8802
city: Hefei
country: China
facility: Site 8805
city: Hefei
country: China
facility: Site No. 8808
city: Hefei
country: China
facility: Site No.8815
city: Nanjing
country: China
facility: Site No. 8801
city: Qingdao
country: China
facility: Site 8833
city: Shanghai
country: China
facility: Site 8806
city: Shanghai
country: China
facility: Site 8822
city: Shanghai
country: China
facility: Site 8831
city: Xi'an
country: China
facility: Site No. 8823
city: Xi'an
country: China
facility: Site No. 8825
city: Bondy
country: France
facility: Site No. 9013
city: Bordeaux
country: France
facility: Site No. 9005
city: Créteil
country: France
facility: Site No. 9003
city: Lille
country: France
facility: Site No. 9006
city: Montpellier
country: France
facility: Site 9012
city: Nantes
country: France
facility: Site No. 9008
city: Nice
country: France
facility: Site No. 9010
city: Paris
country: France
facility: Site No. 9007
city: Paris
country: France
facility: Site No. 9014
city: Rennes
country: France
facility: Site No. 9011
city: Strasbourg
country: France
facility: Site No. 9001
city: Toulouse
country: France
facility: Site No. 9002
city: Vandœuvre-lès-Nancy
country: France
facility: Site No. 9009
city: Aachen
country: Germany
facility: Site No. 9111
city: Bonn
country: Germany
facility: Site No. 9113
city: Dresden
country: Germany
facility: Site No. 9109
city: Frankfurt am Main
country: Germany
facility: Site No. 9108
city: Hamburg
country: Germany
facility: Site No. 9106
city: Hannöver
country: Germany
facility: Site No 9105
city: Heidelberg
country: Germany
facility: Site No. 9112
city: Mainz
country: Germany
facility: Site No. 9101
city: München
country: Germany
facility: Site No. 9102
city: Tübingen
country: Germany
facility: Site No. 9104
city: Ulm
country: Germany
facility: Site No. 9110
city: Hong Kong
country: Hong Kong
facility: Site No. 8601
city: Afula
country: Israel
facility: Site No. 9707
city: Haifa
country: Israel
facility: Site 9704
city: Haifa
country: Israel
facility: Site No. 9702
city: Jerusalem
country: Israel
facility: Site No. 9705
city: Ramat-Gan
country: Israel
facility: Site No. 9703
city: Tel Aviv
country: Israel
facility: Site No. 9706
city: Modena
country: Italy
facility: Site No.9205
city: Napoli
country: Italy
facility: Site No. 9204
city: Palermo
country: Italy
facility: Site No. 9201
city: Parma
country: Italy
facility: Site No. 9203
city: Ansan
country: Korea, Republic of
facility: Site No. 8208
city: Bucheon
country: Korea, Republic of
facility: Site No. 8211
city: Busan
country: Korea, Republic of
facility: Site No. 8201
city: Daegu
country: Korea, Republic of
facility: Site 8216
city: Daegu
country: Korea, Republic of
facility: Site No. 8207
city: Daegu
country: Korea, Republic of
facility: Site No. 8213
city: Daegu
country: Korea, Republic of
facility: Site No. 8220
city: Goyang
country: Korea, Republic of
facility: Site 8224
city: Jinju-si
country: Korea, Republic of
facility: Site No. 8221
city: Pusan
country: Korea, Republic of
facility: Site No. 8218
city: Seongnam-si
country: Korea, Republic of
facility: Site No. 8219
city: Seongnam
country: Korea, Republic of
facility: Site No. 8222
city: Seoul
country: Korea, Republic of
facility: Site No. 8202
city: Seoul
country: Korea, Republic of
facility: Site No. 8203
city: Seoul
country: Korea, Republic of
facility: Site No. 8205
city: Seoul
country: Korea, Republic of
facility: Site No. 8209
city: Seoul
country: Korea, Republic of
facility: Site No. 8212
city: Seoul
country: Korea, Republic of
facility: Site No. 8215
city: Seoul
country: Korea, Republic of
facility: Site No. 8223
city: Suwon
country: Korea, Republic of
facility: Site No. 8210
city: Ulsan
country: Korea, Republic of
facility: Site No. 8217
city: Auckland
country: New Zealand
facility: Auckland City Hospital
city: Christchurch
country: New Zealand
facility: Site No. 8902
city: Coimbra
country: Portugal
facility: Site No. 9404
city: Coimbra
country: Portugal
facility: Site No. 9405
city: Lisboa
country: Portugal
facility: Site No. 9403
city: Porto
country: Portugal
facility: Site No. 9401
city: Porto
country: Portugal
facility: Site No. 9402
city: Singapore
country: Singapore
facility: Site 8702
city: Singapore
country: Singapore
facility: Site 8703
city: Singapore
country: Singapore
facility: Site No. 8701
city: Kaohsiung
country: Taiwan
facility: Site No. 8305
city: Linkou
country: Taiwan
facility: Site No. 8307
city: Taichung
country: Taiwan
facility: Site No. 8306
city: Tainan City
country: Taiwan
facility: Site No. 8302
city: Taipei
country: Taiwan
facility: Site No. 8301
city: Taipei
country: Taiwan
facility: Site No. 8303
city: Bangkok
country: Thailand
facility: Site No. 8502
city: Bangkok
country: Thailand
facility: Site No. 8505
city: Chiang Mai
country: Thailand
facility: Site No. 8503
city: Hat Yai
country: Thailand
facility: Site No. 8507
city: Khon Kaen
country: Thailand
facility: Site No. 8501
city: Phitsanulok
country: Thailand
facility: Site No. 8506
city: Birmingham
country: United Kingdom
facility: Site No. 9501
city: Guildford
country: United Kingdom
facility: Site No. 9505
city: Leeds
country: United Kingdom
facility: Site No. 9503
city: London
country: United Kingdom
facility: Site No. 9502
city: London
country: United Kingdom
facility: Site No. 9504
city: London
country: United Kingdom
facility: Site No. 9506
Study officials:
affiliation: SillaJen, Inc.
name: SillaJen Medical
role: STUDY_DIRECTOR
References: