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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02562755
Recruitment Status : Active, not recruiting
First Posted : September 29, 2015
Last Update Posted : August 12, 2019
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Hepatocellular Carcinoma (HCC) Biological: Pexastimogene Devacirepvec (Pexa Vec) Drug: Sorafenib Phase 3

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 600 patients will be randomly assigned to 2 treatment arms in a 1:1 ratio (300 in each arm) to reach at least 570 evaluable patients.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 600 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : October 2015
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Sorafenib

Arm Intervention/treatment
Experimental: Pexa-Vec followed by Sorafenib
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)
Pexa-Vec is a vaccinia virus based oncolytic immunotherapy designed to stimulate the immune system following infection and replication within tumor cells.
Other Name: JX-594

Drug: 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.

Other Name: Nexavar

Active Comparator: Sorafenib
Sorafenib (400 mg twice daily) begins on Day 1.
Drug: 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.

Other Name: Nexavar




Primary Outcome Measures :
  1. Overall Survival [ Time Frame: From the date of randomization to the date of death due to any cause up to study completion (approximately 53 months). ]

Secondary Outcome Measures :
  1. Time to Progression (TTP) [ Time Frame: From date of randomization to the date of first documented radiographic tumor progression up to 53 months. ]
  2. Progression Free Survival (PFS) [ Time Frame: From date of randomization to the date of first documented radiographic tumor progression or death, whichever occurs first, assessed up to 53 months. ]
  3. Overall Response Rate (ORR) [ Time Frame: From the date of randomization until disease progression, up to 53 months. ]
  4. Disease Control Rate (DCR) [ Time Frame: From date of randomization to end of participation in the study up to 53 months. ]
    Proportion of patients whose best overall response during their participation in the study is either CR, PR, or stable disease (SD).

  5. Incidence of Adverse Events (AE) and Serious Adverse Events (SAE) [ Time Frame: From date of randomization to end of participation in the study, up to 53 months. ]
    Assessed by the NCI CTCAE (version 4.03). Incidence of AEs and SAEs will be reported.

  6. Time to Symptomatic Progression (TSP) [ Time Frame: Time from randomization until the first documented event of symptomatic progression, up to 53 months.. ]

Other Outcome Measures:
  1. Exploratory Outcomes - Duration of Overall Response (DOR) [ Time Frame: From date of first documented response (CR or PR) to date of first documented disease progression or death due to underlying cancer, up to 53 months. ]
  2. Exploratory Outcomes - Time to Initial Response (TIR) [ Time Frame: From date of randomization to date of first documented response (CR or PR), up to 53 months. ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02562755


Locations
Hide Hide 142 study locations
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United States, Alabama
University of Alabama
Birmingham, Alabama, United States, 35294
United States, Arizona
Mayo Clinic Arizona
Scottsdale, Arizona, United States, 85259
United States, California
UC Irvine Medical Center
Orange, California, United States, 92868
Stanford University School of Medicine
Palo Alto, California, United States, 94304
United States, Florida
University of Florida Shands Hospital
Gainesville, Florida, United States, 32608
United States, Illinois
University of Chicago
Chicago, Illinois, United States, 60637
United States, Kansas
University of Kansas Cancer Center
Kansas City, Kansas, United States, 66205
United States, Kentucky
University of Louisville
Louisville, Kentucky, United States, 40202
United States, Louisiana
Tulane University Health Sciences Center
New Orleans, Louisiana, United States, 70112
United States, Maryland
Mercy Medical Center, Inc.
Baltimore, Maryland, United States, 21202
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, Missouri
Kansas City Research Institute
Kansas City, Missouri, United States, 64131
Saint Louis University
Saint Louis, Missouri, United States, 63104
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
United States, Montana
Billings Clinic
Billings, Montana, United States, 59101
United States, New Jersey
Morristown Medical Center
Morristown, New Jersey, United States, 07960
St. Joseph's Hospital
Paterson, New Jersey, United States, 07503
United States, Ohio
Ohio State University
Columbus, Ohio, United States, 43210
United States, Pennsylvania
Hospital of The University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
United States, Rhode Island
Rhode Island Hospital
Providence, Rhode Island, United States, 02903
United States, Tennessee
University of Tennessee Medical Center
Knoxville, Tennessee, United States, 37920
United States, Texas
University of Texas Southwestern Medical Center
Dallas, Texas, United States, 75390
United States, Washington
Benaroya Research Institute at Virginia Mason Hospital
Seattle, Washington, United States, 98101
Australia
Site No. 8409
Adelaide, Australia
Site No. 8412
Adelaide, Australia
Site No. 8403
Brisbane, Australia
Site No. 8401
Camperdown, Australia
Site No. 8407
Clayton, Australia
Site No. 8406
Concord, Australia
Site No. 8408
Fitzroy, Australia
Site No. 8405
Footscray, Australia
Site No. 8414
Heidelberg, Australia
Site No. 8411
Melbourne, Australia
Site No. 8402
Parkville, Australia
Site No. 8415
Perth, Australia
Site No. 8413
Sydney, Australia
Canada, Alberta
University of Alberta Hospital
Edmonton, Alberta, Canada, T6G 2B7
Canada, Ontario
Juravinski Cancer Centre
Hamilton, Ontario, Canada, L8V 1C3
Sunnybrook Health Sciences Centre
Toronto, Ontario, Canada, M4N 3M5
China
Site 8829
Changchun, China
Site No. 8821
Changsha, China
Site 8811
Fuzhou, China
Site 8820
Fuzhou, China
Site No.8816
Guangdong, China
Site 8827
Guangzhou, China
Site No.8828
Guangzhou, China
Site 8832
Hangzhou, China
Site No. 8802
Harbin, China
Site 8805
Hefei, China
Site No. 8808
Hefei, China
Site No.8815
Hefei, China
Site No. 8801
Nanjing, China
Site 8833
Qingdao, China
Site 8806
Shanghai, China
Site 8822
Shanghai, China
Site 8831
Shanghai, China
Site No. 8823
Xi'an, China
Site No. 8825
Xi'an, China
France
Site No. 9013
Bondy, France
Site No. 9005
Bordeaux, France
Site No. 9003
Créteil, France
Site No. 9006
Lille, France
Site 9012
Montpellier, France
Site No. 9008
Nantes, France
Site No. 9010
Nice, France
Site No. 9007
Paris, France
Site No. 9014
Paris, France
Site No. 9011
Rennes, France
Site No. 9001
Strasbourg, France
Site No. 9002
Toulouse, France
Site No. 9009
Vandœuvre-lès-Nancy, France
Germany
Site No. 9111
Aachen, Germany
Site No. 9113
Bonn, Germany
Site No. 9109
Dresden, Germany
Site No. 9108
Frankfurt am Main, Germany
Site No. 9106
Hamburg, Germany
Site No 9105
Hannöver, Germany
Site No. 9112
Heidelberg, Germany
Site No. 9101
Mainz, Germany
Site No. 9102
München, Germany
Site No. 9104
Tübingen, Germany
Site No. 9110
Ulm, Germany
Hong Kong
Site No. 8601
Hong Kong, Hong Kong
Israel
Site No. 9707
Afula, Israel
Site 9704
Haifa, Israel
Site No. 9702
Haifa, Israel
Site No. 9705
Jerusalem, Israel
Site No. 9703
Ramat-Gan, Israel
Site No. 9706
Tel Aviv, Israel
Italy
Site No.9205
Modena, Italy
Site No. 9204
Napoli, Italy
Site No. 9201
Palermo, Italy
Site No. 9203
Parma, Italy
Korea, Republic of
Site No. 8208
Ansan, Korea, Republic of
Site No. 8211
Bucheon, Korea, Republic of
Site No. 8201
Busan, Korea, Republic of
Site 8216
Daegu, Korea, Republic of
Site No. 8207
Daegu, Korea, Republic of
Site No. 8213
Daegu, Korea, Republic of
Site No. 8220
Daegu, Korea, Republic of
Site 8224
Goyang, Korea, Republic of
Site No. 8221
Jinju-si, Korea, Republic of
Site No. 8218
Pusan, Korea, Republic of
Site No. 8219
Seongnam-si, Korea, Republic of
Site No. 8222
Seongnam, Korea, Republic of
Site No. 8202
Seoul, Korea, Republic of
Site No. 8203
Seoul, Korea, Republic of
Site No. 8205
Seoul, Korea, Republic of
Site No. 8209
Seoul, Korea, Republic of
Site No. 8212
Seoul, Korea, Republic of
Site No. 8215
Seoul, Korea, Republic of
Site No. 8223
Seoul, Korea, Republic of
Site No. 8210
Suwon, Korea, Republic of
Site No. 8217
Ulsan, Korea, Republic of
New Zealand
Auckland City Hospital
Auckland, New Zealand, 1142
Site No. 8902
Christchurch, New Zealand
Portugal
Site No. 9404
Coimbra, Portugal
Site No. 9405
Coimbra, Portugal
Site No. 9403
Lisboa, Portugal
Site No. 9401
Porto, Portugal
Site No. 9402
Porto, Portugal
Singapore
Site 8702
Singapore, Singapore
Site 8703
Singapore, Singapore
Site No. 8701
Singapore, Singapore
Taiwan
Site No. 8305
Kaohsiung, Taiwan
Site No. 8307
Linkou, Taiwan
Site No. 8306
Taichung, Taiwan
Site No. 8302
Tainan City, Taiwan
Site No. 8301
Taipei, Taiwan
Site No. 8303
Taipei, Taiwan
Thailand
Site No. 8502
Bangkok, Thailand
Site No. 8505
Bangkok, Thailand
Site No. 8503
Chiang Mai, Thailand
Site No. 8507
Hat Yai, Thailand
Site No. 8501
Khon Kaen, Thailand
Site No. 8506
Phitsanulok, Thailand
United Kingdom
Site No. 9501
Birmingham, United Kingdom
Site No. 9505
Guildford, United Kingdom
Site No. 9503
Leeds, United Kingdom
Site No. 9502
London, United Kingdom
Site No. 9504
London, United Kingdom
Site No. 9506
London, United Kingdom
Sponsors and Collaborators
SillaJen, Inc.
Investigators
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Study Director: Hyuk Chan KWON, MD SillaJen, Inc.
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Responsible Party: SillaJen, Inc.
ClinicalTrials.gov Identifier: NCT02562755    
Other Study ID Numbers: JX594-HEP024
First Posted: September 29, 2015    Key Record Dates
Last Update Posted: August 12, 2019
Last Verified: August 2019
Keywords provided by SillaJen, Inc.:
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
Additional relevant MeSH terms:
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Vaccinia
Carcinoma
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Poxviridae Infections
DNA Virus Infections
Virus Diseases
Sorafenib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action