NCT02562755

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.

Trial Health

98
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Strong global presence with extensive site network
Enrollment
459

participants targeted

Target at P50-P75 for phase_3

Timeline
Completed

Started Oct 2015

Longer than P75 for phase_3

Geographic Reach
16 countries

142 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

September 24, 2015

Completed
5 days until next milestone

First Posted

Study publicly available on registry

September 29, 2015

Completed
2 days until next milestone

Study Start

First participant enrolled

October 1, 2015

Completed
4.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2020

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2020

Completed
6 months until next milestone

Results Posted

Study results publicly available

December 16, 2020

Completed
Last Updated

December 16, 2020

Status Verified

December 1, 2020

Enrollment Period

4.8 years

First QC Date

September 24, 2015

Results QC Date

September 22, 2020

Last Update Submit

December 11, 2020

Conditions

Keywords

Hepatocellular Carcinoma (HCC)Pexastimogene Devacirepvec (Pexa-Vec)SorafenibGM-CSF therapyThymidine Kinase-Deactivated Vaccinia VirusOncologyRecombinant Vaccinia VirusOncolytic Virus TherapyOncolytic virotherapy

Outcome Measures

Primary Outcomes (1)

  • Overall Response Rate (ORR)

    Percentage of participants who showed overall response during their participation in the study. Per Modified Response Evaluation Criteria In Solid Tumors Criteria (mRECIST) and assessed by tri-phasic contrast enhanced CT: Complete Response (CR), Disappearance of intratumoral enhancing area; Partial Response (PR), \>=30% decrease in the sum of the diameters of enhancing area; Overall Response (OR) = CR + PR.

    From date of randomization to the date of first documented radiographic tumor progression up to 53 months

Study Arms (2)

Pexa-Vec followed by Sorafenib

EXPERIMENTAL

Pexa-Vec (pexastimogene devacirepvec) will be administered as 3 bi-weekly intratumoral (IT) injections of 1e9 pfu at day 1 and weeks 2 and 4, followed by sorafenib at Week 6.

Biological: Pexastimogene Devacirepvec (Pexa Vec)Drug: Sorafenib

Sorafenib

ACTIVE COMPARATOR

Sorafenib (400 mg twice daily) begins on Day 1.

Drug: Sorafenib

Interventions

Pexa-Vec is a vaccinia virus based oncolytic immunotherapy designed to stimulate the immune system following infection and replication within tumor cells.

Also known as: JX-594
Pexa-Vec followed by Sorafenib

Sorafenib belongs to the pharmacotherapeutic group of antineoplastic agents, protein kinase inhibitors, ATC code: L01XE05. Sorafenib is a multi-kinase inhibitor which has demonstrated both anti-proliferative and anti-angiogenic properties in vitro and in vivo. Sorafenib is approved for the treatment of advanced HCC and is the Standard Of Care for this disease.

Also known as: Nexavar
Pexa-Vec followed by SorafenibSorafenib

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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:

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (142)

University of Alabama

Birmingham, Alabama, 35294, United States

Location

Mayo Clinic Arizona

Scottsdale, Arizona, 85259, United States

Location

UC Irvine Medical Center

Orange, California, 92868, United States

Location

Stanford University School of Medicine

Palo Alto, California, 94304, United States

Location

University of Florida Shands Hospital

Gainesville, Florida, 32608, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

University of Kansas Cancer Center

Kansas City, Kansas, 66205, United States

Location

University of Louisville

Louisville, Kentucky, 40202, United States

Location

Tulane University Health Sciences Center

New Orleans, Louisiana, 70112, United States

Location

Mercy Medical Center, Inc.

Baltimore, Maryland, 21202, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Kansas City Research Institute

Kansas City, Missouri, 64131, United States

Location

Saint Louis University

St Louis, Missouri, 63104, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Billings Clinic

Billings, Montana, 59101, United States

Location

Morristown Medical Center

Morristown, New Jersey, 07960, United States

Location

St. Joseph's Hospital

Paterson, New Jersey, 07503, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

Hospital of The University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

University of Tennessee Medical Center

Knoxville, Tennessee, 37920, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Benaroya Research Institute at Virginia Mason Hospital

Seattle, Washington, 98101, United States

Location

Site No. 8409

Adelaide, Australia

Location

Site No. 8412

Adelaide, Australia

Location

Site No. 8403

Brisbane, Australia

Location

Site No. 8401

Camperdown, Australia

Location

Site No. 8407

Clayton, Australia

Location

Site No. 8406

Concord, Australia

Location

Site No. 8408

Fitzroy, Australia

Location

Site No. 8405

Footscray, Australia

Location

Site No. 8414

Heidelberg, Australia

Location

Site No. 8411

Melbourne, Australia

Location

Site No. 8402

Parkville, Australia

Location

Site No. 8415

Perth, Australia

Location

Site No. 8413

Sydney, Australia

Location

University of Alberta Hospital

Edmonton, Alberta, T6G 2B7, Canada

Location

Juravinski Cancer Centre

Hamilton, Ontario, L8V 1C3, Canada

Location

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

Location

Site 8829

Changchun, China

Location

Site No. 8821

Changsha, China

Location

Site 8811

Fuzhou, China

Location

Site 8820

Fuzhou, China

Location

Site No.8816

Guangdong, China

Location

Site 8827

Guangzhou, China

Location

Site No.8828

Guangzhou, China

Location

Site 8832

Hangzhou, China

Location

Site No. 8802

Harbin, China

Location

Site 8805

Hefei, China

Location

Site No. 8808

Hefei, China

Location

Site No.8815

Hefei, China

Location

Site No. 8801

Nanjing, China

Location

Site 8833

Qingdao, China

Location

Site 8806

Shanghai, China

Location

Site 8822

Shanghai, China

Location

Site 8831

Shanghai, China

Location

Site No. 8823

Xi'an, China

Location

Site No. 8825

Xi'an, China

Location

Site No. 9013

Bondy, France

Location

Site No. 9005

Bordeaux, France

Location

Site No. 9003

Créteil, France

Location

Site No. 9006

Lille, France

Location

Site 9012

Montpellier, France

Location

Site No. 9008

Nantes, France

Location

Site No. 9010

Nice, France

Location

Site No. 9007

Paris, France

Location

Site No. 9014

Paris, France

Location

Site No. 9011

Rennes, France

Location

Site No. 9001

Strasbourg, France

Location

Site No. 9002

Toulouse, France

Location

Site No. 9009

VandÅ“uvre-lès-Nancy, France

Location

Site No. 9111

Aachen, Germany

Location

Site No. 9113

Bonn, Germany

Location

Site No. 9109

Dresden, Germany

Location

Site No. 9108

Frankfurt am Main, Germany

Location

Site No. 9106

Hamburg, Germany

Location

Site No 9105

Hannover, Germany

Location

Site No. 9112

Heidelberg, Germany

Location

Site No. 9101

Mainz, Germany

Location

Site No. 9102

MĂ¼nchen, Germany

Location

Site No. 9104

TĂ¼bingen, Germany

Location

Site No. 9110

Ulm, Germany

Location

Site No. 8601

Hong Kong, Hong Kong

Location

Site No. 9707

Afula, Israel

Location

Site 9704

Haifa, Israel

Location

Site No. 9702

Haifa, Israel

Location

Site No. 9705

Jerusalem, Israel

Location

Site No. 9703

Ramat Gan, Israel

Location

Site No. 9706

Tel Aviv, Israel

Location

Site No.9205

Modena, Italy

Location

Site No. 9204

Napoli, Italy

Location

Site No. 9201

Palermo, Italy

Location

Site No. 9203

Parma, Italy

Location

Auckland City Hospital

Auckland, 1142, New Zealand

Location

Site No. 8902

Christchurch, New Zealand

Location

Site No. 9404

Coimbra, Portugal

Location

Site No. 9405

Coimbra, Portugal

Location

Site No. 9403

Lisbon, Portugal

Location

Site No. 9401

Porto, Portugal

Location

Site No. 9402

Porto, Portugal

Location

Site 8702

Singapore, Singapore

Location

Site 8703

Singapore, Singapore

Location

Site No. 8701

Singapore, Singapore

Location

Site No. 8208

Ansan, South Korea

Location

Site No. 8211

Bucheon-si, South Korea

Location

Site No. 8201

Busan, South Korea

Location

Site 8216

Daegu, South Korea

Location

Site No. 8207

Daegu, South Korea

Location

Site No. 8213

Daegu, South Korea

Location

Site No. 8220

Daegu, South Korea

Location

Site 8224

Goyang, South Korea

Location

Site No. 8221

Jinju, South Korea

Location

Site No. 8218

Pusan, South Korea

Location

Site No. 8222

Seongnam, South Korea

Location

Site No. 8219

Seongnam-si, South Korea

Location

Site No. 8202

Seoul, South Korea

Location

Site No. 8203

Seoul, South Korea

Location

Site No. 8205

Seoul, South Korea

Location

Site No. 8209

Seoul, South Korea

Location

Site No. 8212

Seoul, South Korea

Location

Site No. 8215

Seoul, South Korea

Location

Site No. 8223

Seoul, South Korea

Location

Site No. 8210

Suwon, South Korea

Location

Site No. 8217

Ulsan, South Korea

Location

Site No. 8305

Kaohsiung City, Taiwan

Location

Site No. 8307

Linkou District, Taiwan

Location

Site No. 8306

Taichung, Taiwan

Location

Site No. 8302

Tainan, Taiwan

Location

Site No. 8301

Taipei, Taiwan

Location

Site No. 8303

Taipei, Taiwan

Location

Site No. 8502

Bangkok, Thailand

Location

Site No. 8505

Bangkok, Thailand

Location

Site No. 8503

Chiang Mai, Thailand

Location

Site No. 8507

Hat Yai, Thailand

Location

Site No. 8501

Khon Kaen, Thailand

Location

Site No. 8506

Phitsanulok, Thailand

Location

Site No. 9501

Birmingham, United Kingdom

Location

Site No. 9505

Guildford, United Kingdom

Location

Site No. 9503

Leeds, United Kingdom

Location

Site No. 9502

London, United Kingdom

Location

Site No. 9504

London, United Kingdom

Location

Site No. 9506

London, United Kingdom

Location

MeSH Terms

Conditions

Carcinoma, HepatocellularNeoplasmsVaccinia

Interventions

Sorafenib

Condition Hierarchy (Ancestors)

AdenocarcinomaCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeLiver NeoplasmsDigestive System NeoplasmsNeoplasms by SiteDigestive System DiseasesLiver DiseasesPoxviridae InfectionsDNA Virus InfectionsVirus DiseasesInfections

Intervention Hierarchy (Ancestors)

Phenylurea CompoundsUreaAmidesOrganic ChemicalsBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsNiacinamideNicotinic AcidsAcids, HeterocyclicHeterocyclic CompoundsPyridinesHeterocyclic Compounds, 1-Ring

Results Point of Contact

Title
Kyoung Soo Ha, Senior Medical Director
Organization
SillaJen Biotherapeutics Inc.

Study Officials

  • SillaJen Medical

    SillaJen, Inc.

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 24, 2015

First Posted

September 29, 2015

Study Start

October 1, 2015

Primary Completion

July 1, 2020

Study Completion

July 1, 2020

Last Updated

December 16, 2020

Results First Posted

December 16, 2020

Record last verified: 2020-12

Data Sharing

IPD Sharing
Will not share

Locations