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

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ClinicalTrials.gov Identifier: NCT02562755
Recruitment Status : Recruiting
First Posted : September 29, 2015
Last Update Posted : December 19, 2018
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.


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 : July 2019
Estimated Study Completion Date : October 2019

Resource links provided by the National Library of Medicine


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

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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


Contacts
Contact: Angelica Craighead (415) 814-9865 patient_inquiry@sillajen.com

  Hide Study Locations
Locations
United States, Alabama
University of Alabama Recruiting
Birmingham, Alabama, United States, 35294
Principal Investigator: Sudha Kodali, MD         
United States, Arizona
Mayo Clinic Arizona Active, not recruiting
Scottsdale, Arizona, United States, 85259
United States, California
UC Irvine Medical Center Recruiting
Orange, California, United States, 92868
Principal Investigator: Nadine Abi-Jaoudeh, MD         
Stanford University School of Medicine Recruiting
Palo Alto, California, United States, 94304
Principal Investigator: Nishita Kothary, MD         
United States, Florida
University of Florida Shands Hospital Recruiting
Gainesville, Florida, United States, 32608
Principal Investigator: Roniel Cabrera, MD         
United States, Illinois
University of Chicago Recruiting
Chicago, Illinois, United States, 60637
Principal Investigator: Manish Sharma         
United States, Kansas
University of Kansas Cancer Center Active, not recruiting
Kansas City, Kansas, United States, 66205
United States, Kentucky
University of Louisville Recruiting
Louisville, Kentucky, United States, 40202
Principal Investigator: Robert Martin, MD         
United States, Louisiana
Tulane University Health Sciences Center Recruiting
New Orleans, Louisiana, United States, 70112
Principal Investigator: Fredric Regenstein, MD         
United States, Maryland
Mercy Medical Center, Inc. Recruiting
Baltimore, Maryland, United States, 21202
Principal Investigator: Paul Thuluvath, MD         
United States, Minnesota
University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Principal Investigator: Edward Greeno, MD         
United States, Missouri
Kansas City Research Institute Recruiting
Kansas City, Missouri, United States, 64131
Principal Investigator: Bradley Freilich, MD         
Saint Louis University Recruiting
Saint Louis, Missouri, United States, 63104
Principal Investigator: Alex Befeler, MD         
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Principal Investigator: Benjamin Tan, M.D.         
United States, Montana
Billings Clinic Recruiting
Billings, Montana, United States, 59101
Principal Investigator: Michael Kidd, MD         
United States, New Jersey
Morristown Medical Center Recruiting
Morristown, New Jersey, United States, 07960
Principal Investigator: Lawrence Harrison, MD         
St. Joseph's Hospital Active, not recruiting
Paterson, New Jersey, United States, 07503
United States, Ohio
Ohio State University Recruiting
Columbus, Ohio, United States, 43210
Principal Investigator: Anne Noonan, MD         
United States, Pennsylvania
Hospital of The University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Principal Investigator: William Stavropoulos, MD         
United States, Rhode Island
Rhode Island Hospital Completed
Providence, Rhode Island, United States, 02903
United States, South Carolina
University of South Carolina Recruiting
Charleston, South Carolina, United States, 29208
Principal Investigator: Juan Camacho, MD         
United States, Tennessee
University of Tennessee Medical Center Recruiting
Knoxville, Tennessee, United States, 37920
Contact: Laura K Findeiss, MD         
Principal Investigator: Laura K Findeiss, MD         
United States, Texas
University of Texas Southwestern Medical Center Recruiting
Dallas, Texas, United States, 75390
Principal Investigator: Muhammad Beg, MD         
United States, Washington
Benaroya Research Institute at Virginia Mason Hospital Recruiting
Seattle, Washington, United States, 98101
Principal Investigator: Shih-Li Lin, MD         
Australia
Site No. 8409 Recruiting
Adelaide, Australia
Site No. 8412 Recruiting
Adelaide, Australia
Site No. 8403 Recruiting
Brisbane, Australia
Site No. 8401 Recruiting
Camperdown, Australia
Site No. 8407 Active, not recruiting
Clayton, Australia
Site No. 8406 Recruiting
Concord, Australia
Site No. 8408 Active, not recruiting
Fitzroy, Australia
Site No. 8405 Active, not recruiting
Footscray, Australia
Site No. 8414 Recruiting
Heidelberg, Australia
Site No. 8411 Recruiting
Melbourne, Australia
Site No. 8402 Recruiting
Parkville, Australia
Site No. 8415 Active, not recruiting
Perth, Australia
Site No. 8413 Recruiting
Sydney, Australia
Canada, Alberta
University of Alberta Hospital Active, not recruiting
Edmonton, Alberta, Canada, T6G 2B7
Canada, Ontario
Juravinski Cancer Centre Recruiting
Hamilton, Ontario, Canada, L8V 1C3
Principal Investigator: Leyo Ruo, MD         
Sunnybrook Health Sciences Centre Recruiting
Toronto, Ontario, Canada, M4N 3M5
Principal Investigator: Yoo-Joung Ko, MD         
China
Site No. 8821 Recruiting
Changsha, China
Site No.8816 Recruiting
Guangdong, China
Site No.8828 Recruiting
Guangzhou, China
Site No. 8802 Recruiting
Harbin, China
Site No. 8808 Recruiting
Hefei, China
Site No.8815 Recruiting
Hefei, China
Site No. 8801 Recruiting
Nanjing, China
Site 8822 Recruiting
Shanghai, China
Site No. 8823 Recruiting
Xi'an, China
Site No. 8825 Recruiting
Xi'an, China
France
Site No. 9013 Active, not recruiting
Bondy, France
Site No. 9005 Active, not recruiting
Bordeaux, France
Site No. 9003 Active, not recruiting
Créteil, France
Site No. 9006 Active, not recruiting
Lille, France
Site 9012 Active, not recruiting
Montpellier, France
Site No. 9008 Active, not recruiting
Nantes, France
Site No. 9010 Active, not recruiting
Nice, France
Site No. 9007 Active, not recruiting
Paris, France
Site No. 9014 Active, not recruiting
Paris, France
Site No. 9011 Active, not recruiting
Rennes, France
Site No. 9001 Active, not recruiting
Strasbourg, France
Site No. 9002 Active, not recruiting
Toulouse, France
Site No. 9009 Active, not recruiting
Vandœuvre-lès-Nancy, France
Germany
Site No. 9111 Active, not recruiting
Aachen, Germany
Site No. 9113 Active, not recruiting
Bonn, Germany
Site No. 9109 Active, not recruiting
Dresden, Germany
Site No. 9108 Active, not recruiting
Frankfurt am Main, Germany
Site No. 9106 Active, not recruiting
Hamburg, Germany
Site No 9105 Active, not recruiting
Hannöver, Germany
Site No. 9112 Active, not recruiting
Heidelberg, Germany
Site No. 9101 Active, not recruiting
Mainz, Germany
Site No. 9102 Active, not recruiting
München, Germany
Site No. 9104 Active, not recruiting
Tübingen, Germany
Site No. 9110 Active, not recruiting
Ulm, Germany
Hong Kong
Site No. 8601 Recruiting
Hong Kong, Hong Kong
Israel
Site No. 9707 Active, not recruiting
Afula, Israel
Site No. 9702 Active, not recruiting
Haifa, Israel
Site No. 9705 Active, not recruiting
Jerusalem, Israel
Site No. 9703 Active, not recruiting
Ramat-Gan, Israel
Site No. 9706 Active, not recruiting
Tel Aviv, Israel
Italy
Site No.9205 Active, not recruiting
Modena, Italy
Site No. 9204 Active, not recruiting
Napoli, Italy
Site No. 9201 Active, not recruiting
Palermo, Italy
Site No. 9203 Active, not recruiting
Parma, Italy
Korea, Republic of
Site No. 8208 Recruiting
Ansan, Korea, Republic of
Site No. 8211 Recruiting
Bucheon, Korea, Republic of
Site No. 8201 Recruiting
Busan, Korea, Republic of
Site No. 8207 Recruiting
Daegu, Korea, Republic of
Site No. 8213 Recruiting
Daegu, Korea, Republic of
Site No. 8220 Recruiting
Daegu, Korea, Republic of
Site No. 8221 Recruiting
Jinju-si, Korea, Republic of
Site No. 8218 Recruiting
Pusan, Korea, Republic of
Site No. 8219 Recruiting
Seongnam-si, Korea, Republic of
Site No. 8222 Recruiting
Seongnam, Korea, Republic of
Site No. 8202 Recruiting
Seoul, Korea, Republic of
Site No. 8203 Recruiting
Seoul, Korea, Republic of
Site No. 8205 Recruiting
Seoul, Korea, Republic of
Site No. 8209 Recruiting
Seoul, Korea, Republic of
Site No. 8212 Recruiting
Seoul, Korea, Republic of
Site No. 8215 Recruiting
Seoul, Korea, Republic of
Site No. 8223 Recruiting
Seoul, Korea, Republic of
Site No. 8210 Recruiting
Suwon, Korea, Republic of
Site No. 8217 Recruiting
Ulsan, Korea, Republic of
New Zealand
Auckland City Hospital Recruiting
Auckland, New Zealand, 1142
Contact: Edward Gane, MD         
Principal Investigator: Edward Gane, MD         
Site No. 8902 Recruiting
Christchurch, New Zealand
Portugal
Site No. 9404 Active, not recruiting
Coimbra, Portugal
Site No. 9405 Active, not recruiting
Coimbra, Portugal
Site No. 9403 Completed
Lisboa, Portugal
Site No. 9401 Active, not recruiting
Porto, Portugal
Site No. 9402 Active, not recruiting
Porto, Portugal
Singapore
Site No. 8701 Completed
Singapore, Singapore
Taiwan
Site No. 8305 Active, not recruiting
Kaoshiung, Taiwan
Site No. 8307 Recruiting
Linkou, Taiwan
Site No. 8306 Recruiting
Taichung, Taiwan
Site No. 8302 Active, not recruiting
Tainan City, Taiwan
Site No. 8301 Active, not recruiting
Taipei, Taiwan
Site No. 8303 Recruiting
Taipei, Taiwan
Thailand
Site No. 8502 Active, not recruiting
Bangkok, Thailand
Site No. 8505 Active, not recruiting
Bangkok, Thailand
Site No. 8503 Active, not recruiting
Chiang Mai, Thailand
Site No. 8507 Active, not recruiting
Hat Yai, Thailand
Site No. 8501 Active, not recruiting
Khon Kaen, Thailand
Site No. 8506 Active, not recruiting
Phitsanulok, Thailand
United Kingdom
Site No. 9501 Active, not recruiting
Birmingham, United Kingdom
Site No. 9505 Active, not recruiting
Guildford, United Kingdom
Site No. 9503 Active, not recruiting
Leeds, United Kingdom
Site No. 9502 Active, not recruiting
London, United Kingdom
Site No. 9504 Active, not recruiting
London, United Kingdom
Site No. 9506 Active, not recruiting
London, United Kingdom
Sponsors and Collaborators
SillaJen, Inc.
Investigators
Study Director: Hyuk Chan KWON, MD SillaJen, Inc.

Responsible Party: SillaJen, Inc.
ClinicalTrials.gov Identifier: NCT02562755     History of Changes
Other Study ID Numbers: JX594-HEP024
First Posted: September 29, 2015    Key Record Dates
Last Update Posted: December 19, 2018
Last Verified: December 2018

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:
Carcinoma
Carcinoma, Hepatocellular
Vaccinia
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
Niacinamide
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs