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Hepatocellular Carcinoma Study Comparing Vaccinia Virus Based Immunotherapy Plus Sorafenib vs Sorafenib Alone

Phase 3
Completed
Conditions
Hepatocellular Carcinoma (HCC)
Interventions
Biological: Pexastimogene Devacirepvec (Pexa Vec)
Registration Number
NCT02562755
Lead Sponsor
SillaJen, Inc.
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
459
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Pexa-Vec followed by SorafenibPexastimogene Devacirepvec (Pexa Vec)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.
Pexa-Vec followed by SorafenibSorafenibPexa-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.
SorafenibSorafenibSorafenib (400 mg twice daily) begins on Day 1.
Primary Outcome Measures
NameTimeMethod
Overall Response Rate (ORR)From date of randomization to the date of first documented radiographic tumor progression up to 53 months

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.

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (142)

Site No. 8306

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Taichung, Taiwan

Site No. 8505

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Bangkok, Thailand

Site No. 8503

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Chiang Mai, Thailand

Site No. 8301

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Taipei, Taiwan

Site No. 8303

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Taipei, Taiwan

Site No. 8507

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Hat Yai, Thailand

Site No. 8501

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Khon Kaen, Thailand

Site No. 8506

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Phitsanulok, Thailand

Site No. 8414

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Heidelberg, Australia

Site 9012

🇫🇷

Montpellier, France

Site No. 8211

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Bucheon, Korea, Republic of

Site No. 8403

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Brisbane, Australia

Mayo Clinic Arizona

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Scottsdale, Arizona, United States

Site No. 8401

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Camperdown, Australia

University of Tennessee Medical Center

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Knoxville, Tennessee, United States

Site No. 8406

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Concord, Australia

University of Florida Shands Hospital

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Gainesville, Florida, United States

Billings Clinic

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Billings, Montana, United States

Site No. 8411

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Melbourne, Australia

Site No. 8402

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Parkville, Australia

University of Kansas Cancer Center

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Kansas City, Kansas, United States

Site No. 9014

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Paris, France

Site No. 8412

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Adelaide, Australia

Site No. 8405

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Footscray, Australia

Stanford University School of Medicine

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Palo Alto, California, United States

Site No. 8821

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Changsha, China

Site No. 8407

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Clayton, Australia

Site No. 9204

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Napoli, Italy

Site No. 8409

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Adelaide, Australia

Site No. 9005

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Bordeaux, France

Site No. 9113

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Bonn, Germany

Site No. 9110

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Ulm, Germany

Site No. 9707

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Afula, Israel

Site No. 9702

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Haifa, Israel

Site No. 9703

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Ramat-Gan, Israel

Site No. 9402

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Porto, Portugal

Site No. 8305

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Kaohsiung, Taiwan

Site 8820

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Fuzhou, China

Site 9704

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Haifa, Israel

University of Alberta Hospital

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Edmonton, Alberta, Canada

Site No. 8205

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Seoul, Korea, Republic of

Site No. 9706

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Tel Aviv, Israel

Site No. 9403

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Lisboa, Portugal

Site No. 9106

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Hamburg, Germany

Site 8224

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Goyang, Korea, Republic of

Site 8216

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Daegu, Korea, Republic of

Site No. 9705

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Jerusalem, Israel

Site No. 9501

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Birmingham, United Kingdom

Site No. 9505

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Guildford, United Kingdom

Site No. 8701

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Singapore, Singapore

Site No. 8307

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Linkou, Taiwan

Site No. 9201

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Palermo, Italy

Site No. 9203

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Parma, Italy

Site No. 8222

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Seongnam, Korea, Republic of

Site No. 9111

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Aachen, Germany

Site No. 9009

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Vandœuvre-lès-Nancy, France

Site No 9105

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Hannöver, Germany

Site No. 9101

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Mainz, Germany

Site No. 8213

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Daegu, Korea, Republic of

Site No. 9405

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Coimbra, Portugal

Site 8702

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Singapore, Singapore

Site No. 8502

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Bangkok, Thailand

Site No.9205

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Modena, Italy

Site No. 9112

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Heidelberg, Germany

Site No. 9102

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München, Germany

Site No. 9104

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Tübingen, Germany

Site No. 8207

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Daegu, Korea, Republic of

Site No. 9404

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Coimbra, Portugal

Site No. 8302

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Tainan City, Taiwan

Site No. 8215

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Seoul, Korea, Republic of

Site No.8815

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Hefei, China

Site 8832

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Hangzhou, China

Site 8833

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Qingdao, China

Site 8806

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Shanghai, China

Site No. 8823

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Xi'an, China

Sunnybrook Health Sciences Centre

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Toronto, Ontario, Canada

Site No. 9013

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Bondy, France

Site No. 8202

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Seoul, Korea, Republic of

Site No. 9502

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London, United Kingdom

Site No. 9503

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Leeds, United Kingdom

Site No. 9007

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Paris, France

Site No. 9008

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Nantes, France

Site No. 9011

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Rennes, France

Auckland City Hospital

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Auckland, New Zealand

Site No. 9504

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London, United Kingdom

Site No. 9006

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Lille, France

Site No. 8201

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Busan, Korea, Republic of

Site No. 8220

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Daegu, Korea, Republic of

Site No. 8212

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Seoul, Korea, Republic of

UC Irvine Medical Center

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Orange, California, United States

Tulane University Health Sciences Center

🇺🇸

New Orleans, Louisiana, United States

Washington University School of Medicine

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Saint Louis, Missouri, United States

Saint Louis University

🇺🇸

Saint Louis, Missouri, United States

Morristown Medical Center

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Morristown, New Jersey, United States

St. Joseph's Hospital

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Paterson, New Jersey, United States

University of Texas Southwestern Medical Center

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Dallas, Texas, United States

Site No. 8408

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Fitzroy, Australia

Site No. 8413

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Sydney, Australia

Site No. 8415

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Perth, Australia

Juravinski Cancer Centre

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Hamilton, Ontario, Canada

Site 8829

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Changchun, China

Site 8811

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Fuzhou, China

Site No.8816

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Guangdong, China

Site 8827

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Guangzhou, China

Site No.8828

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Guangzhou, China

Site 8805

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Hefei, China

Site No. 8802

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Harbin, China

Site No. 8808

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Hefei, China

Site 8822

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Shanghai, China

Site No. 8825

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Xi'an, China

Site 8831

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Shanghai, China

Site No. 9003

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Créteil, France

Site No. 9010

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Nice, France

Site No. 9001

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Strasbourg, France

Site No. 9002

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Toulouse, France

Site No. 9109

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Dresden, Germany

Site No. 9108

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Frankfurt am Main, Germany

Site No. 8208

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Ansan, Korea, Republic of

Site No. 8221

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Jinju-si, Korea, Republic of

Site No. 8218

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Pusan, Korea, Republic of

Site No. 8203

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Seoul, Korea, Republic of

Site No. 8219

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Seongnam-si, Korea, Republic of

Site No. 8209

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Seoul, Korea, Republic of

Site No. 8210

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Suwon, Korea, Republic of

Site No. 8223

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Seoul, Korea, Republic of

Site No. 8217

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Ulsan, Korea, Republic of

Site No. 8902

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Christchurch, New Zealand

Site 8703

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Singapore, Singapore

Site No. 9401

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Porto, Portugal

Site No. 9506

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London, United Kingdom

University of Alabama

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Birmingham, Alabama, United States

University of Chicago

🇺🇸

Chicago, Illinois, United States

University of Louisville

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Louisville, Kentucky, United States

Mercy Medical Center, Inc.

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Baltimore, Maryland, United States

University of Minnesota

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Minneapolis, Minnesota, United States

Kansas City Research Institute

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Kansas City, Missouri, United States

Ohio State University

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Columbus, Ohio, United States

Hospital of The University of Pennsylvania

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Philadelphia, Pennsylvania, United States

Benaroya Research Institute at Virginia Mason Hospital

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Seattle, Washington, United States

Rhode Island Hospital

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Providence, Rhode Island, United States

Site No. 8801

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Nanjing, China

Site No. 8601

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Hong Kong, Hong Kong

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