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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. Identifier: NCT02562755
Recruitment Status : Active, not recruiting
First Posted : September 29, 2015
Last Update Posted : August 12, 2019
Information provided by (Responsible Party):
SillaJen, Inc.

Tracking Information
First Submitted Date  ICMJE September 24, 2015
First Posted Date  ICMJE September 29, 2015
Last Update Posted Date August 12, 2019
Study Start Date  ICMJE October 2015
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 25, 2015)
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). ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 25, 2015)
  • Time to Progression (TTP) [ Time Frame: From date of randomization to the date of first documented radiographic tumor progression up to 53 months. ]
  • 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. ]
  • Overall Response Rate (ORR) [ Time Frame: From the date of randomization until disease progression, up to 53 months. ]
  • 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).
  • 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.
  • Time to Symptomatic Progression (TSP) [ Time Frame: Time from randomization until the first documented event of symptomatic progression, up to 53 months.. ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: September 25, 2015)
  • 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. ]
  • 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. ]
Original Other Pre-specified Outcome Measures Same as current
Descriptive Information
Brief Title  ICMJE Hepatocellular Carcinoma Study Comparing Vaccinia Virus Based Immunotherapy Plus Sorafenib vs Sorafenib Alone
Official Title  ICMJE 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
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 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  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Hepatocellular Carcinoma (HCC)
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • 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)
    • Drug: Sorafenib
  • Active Comparator: Sorafenib
    Sorafenib (400 mg twice daily) begins on Day 1.
    Intervention: Drug: Sorafenib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: September 25, 2015)
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2020
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Canada,   China,   France,   Germany,   Hong Kong,   Israel,   Italy,   Korea, Republic of,   New Zealand,   Portugal,   Singapore,   Taiwan,   Thailand,   United Kingdom,   United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT02562755
Other Study ID Numbers  ICMJE JX594-HEP024
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party SillaJen, Inc.
Study Sponsor  ICMJE SillaJen, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Hyuk Chan KWON, MD SillaJen, Inc.
PRS Account SillaJen, Inc.
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP