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Carcinoma, HepatocellularPhase 2NCT00554372

A Study of Recombinant Vaccinia Virus to Treat Unresectable Primary Hepatocellular Carcinoma

A Phase 2 study testing JX-594: Recombinant vaccinia virus (TK-deletion plus GM-CSF) in people with Carcinoma, Hepatocellular, run by Jennerex Biotherapeutics at 9 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this research study is to determine whether JX-594 (Pexa-Vec) has significant anti-tumoral activity and tolerability in primary hepatocellular carcinoma and to determine the dose to be used in further testing. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Carcinoma, Hepatocellular
What is being tested?
JX-594: Recombinant vaccinia virus (TK-deletion plus GM-CSF)
Type of treatment
Vaccines
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
9 sitesin 3 countries
Study dates
Aug 2008to Feb 2013
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histological confirmation or clinical/laboratory diagnosis of primary hepatocellular carcinoma (HCC)
  • Cancer is not surgically resectable for cure
  • Child Pugh A or B
  • Tumor progression during or after at least one prior HCC treatment regimen (Note: If standard HCC therapies are either medically contraindicated or patient has refused those treatments, the patient may be eligible for this study)
  • Performance Score: KPS score of ≥ 70
  • Anticipated survival of at least 16 weeks
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  • Total bilirubin ≤ 2.5 x ULN
  • AST, ALT < 5.0 x ULN
  • WBC > 2,500 cells/mm3 and < 50,000 cells/mm3 (GCSF treatment allowed)
  • ANC > 1,250 cells/mm3 (GCSF treatment allowed)
  • Hemoglobin ≥ 9 g/dL (RBC transfusion allowed)
  • Platelet count ≥ 50,000 plts/mm3
  • Acceptable coagulation status: INR ≤ 1.5 x ULN
  • Acceptable kidney function: Serum creatinine < 2.0 mg/dL
  • If patients are diabetic or have a screening random glucose > 160 mg/dL, a fasting glucose must be done and patients must be WNL or Grade 1 in order to be eligible for the study
  • For patients who are sexually active: able and willing to abstain from sex during treatment period and for 3 weeks following treatment, and use an acceptable method of birth control for 3 months after last injection with JX-594
  • Able/willing to sign an IRB/IEC/REB-approved written consent form
  • Able and willing to comply with study procedures and follow-up examinations, including compliance with the "Infection Control Guidelines for Patients" (in written consent form)

Who cannot join

  • Current, known extra-hepatic tumors that, in the investigator's medical opinion, are likely to result in significant morbidity or mortality within the next 16 weeks.
  • Pregnant or nursing an infant
  • Known infection with HIV
  • Clinically significant active infection or uncontrolled medical condition considered high risk for investigational new drug treatment
  • Significant immunodeficiency due to underlying illness (e.g. hematological malignancies, congenital immunodeficiencies and/or HIV infection/AIDS) and/or medication (e.g. high-dose systemic corticosteroids)
  • History of exfoliative skin condition (e.g. severe eczema, ectopic dermatitis, or similar skin disorder) that at some stage has required systemic therapy
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  • Clinically significant and/or rapidly accumulating ascites, peri-cardial and/or pleural effusions
  • Liver tumors in a location that would potentially result in significant clinical adverse effects if post-treatment tumor swelling were to occur (e.g. tumors impinging on the biliary tract that could affect drainage)
  • Severe or unstable cardiac disease
  • Current, known CNS malignancy
  • Anti-cancer therapy (e.g. RFA, TACE, PEIT, radioembolization, chemotherapy, surgery, or an investigational drug, etc.) within 4 weeks prior to first treatment
  • Absolute contraindication to undergoing MRI scanning
  • Experienced a severe systemic reaction or side-effect as a result of a previous smallpox vaccination
  • Use of anti-platelet or anti-coagulation medication
  • Use of the following anti-viral agents: ribavirin, adefovir, cidofovir (within 7 days prior to the first treatment), and PEG-IFN (within 14 days prior to the first treatment).
  • Inability or unwillingness to give informed consent or comply with the procedures required in the protocol
  • Patients with household contacts who meet any of these criteria unless alternate living arrangements can be made during the patient's active dosing period and for 7 days following the last dose of study medication:
  • Pregnant or nursing an infant
  • Children < 12 months old
  • History of exfoliative skin condition that at some stage has required systemic therapy
  • Significant immunodeficiency due to underlying illness (e.g. HIV/AIDS) and/or medication

Trial locations and contacts

9 sites in 3 countries.

9 sites in 3 countries

United States5 sites
  • Billings Clinic Cancer Center

    Billings, Montana, 59101

  • The Ohio State University

    Columbus, Ohio, 43210

  • Moores UCSD Cancer Center

    La Jolla, California, 92093

  • University of Pittsburgh Medical Center - Liver Cancer Center

    Pittsburgh, Pennsylvania, 15213

  • Mayo Clinic

    Rochester, Minnesota, 55905

Other trials in United States

South Korea3 sites
  • Pusan National University Hospital

    Busan

  • Samsung Medical Center

    Seoul

  • Shin Chon Severance Hospital / Yonsei University Medical Center

    Seoul

Other trials in South Korea

Canada1 site
  • McMaster University Medical Centre

    Hamilton, Ontario, L8N 1Y3

Other trials in Canada

About this study

Official title: A Phase II-a, Open-Label, Randomized Study of JX-594 (Thymidine Kinase-deleted Vaccinia Virus Plus GM-CSF) Administered by Intratumoral Injection in Patients With Unresectable Primary Hepatocellular Carcinoma

The purpose of this research study is to determine whether JX-594 (Pexa-Vec) has significant anti-tumoral activity and tolerability in primary hepatocellular carcinoma and to determine the dose to be used in further testing.

Read the detailed description

Hepatocellular carcinoma (HCC) is estimated to be the third most common cause of cancer-related deaths world-wide, and the fifth most common cancer diagnosis. According to the National Cancer Institute (NCI), approximately 17,000 new cases of HCC are diagnosed annually in the U.S. In Canada, the predicted incidence for 2007 is 1,350 new cases. In addition, approximately 10,000 new cases are diagnosed per year in S. Korea, 35,000 in the E.U. and 45,000 in Japan.

The five-year survival rate is estimated to be <10% for all HCC patients. Given the poor prognosis of these patients there is a desperate need for new therapies.

Surgical resection and liver transplant are the only curative treatment for HCC. Small HCC tumor(s) (less than 3 cm in diameter) can be resected by hepatectomy, the most effective treatment. Surgery was associated with a reported 50-60% five-year survival rate, but unfortunately was possible in only 10-15% of cases. Liver transplant is considered for patients with tumors that are unresectable but that are still limited exclusively to the liver, have no extracapsular or vascular invasion within the liver, and for whom there are no medical contraindications to transplantation. Patients with unresectable HCC that cannot receive liver transplantation, and who do not require systemic therapy, may be administered percutaneous ethanol injection therapy (PEIT), radiofrequency ablation (RFA), transarterial chemoembolization (TACE), and/or radioembolization, depending on the size of the intrahepatic tumors and the underlying liver function.

HCC may be a good target for IT injection with JX-594 because of the relatively high rate of accessible tumors for injection, the positive response seen in a patient with HCC in a recently completed Phase I study of JX-594 intratumoral injection within the liver, excellent tumor responses in multiple preclinical cancer models, and the lack of effective, tolerable therapy for most patients with HCC who cannot receive curative surgery or immediate liver transplantation. Furthermore, it is speculated that JX-594 replication targets the EGFR pathway, and that it's spread within and between tumors is dependent upon the intratumoral vasculature; HCC has highly activated angiogenesis and EGFR pathways in the majority of cases.

Being tested
JX-594: Recombinant vaccinia virus (TK-deletion plus GM-CSF)
Keywords
Jennerex, HCC, unresectable primary hepatocellular carcinoma, hepatocellular carcinoma, liver cancer, Phase 2, oncolytic virus, Pexa-Vec
Medical subject headings
Carcinoma, Hepatocellular, Liver Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • JX-594: Recombinant vaccinia virus (TK-deletion plus GM-CSF)Genetic

    Patients will be randomized 1:1 to one of two total doses (1e8 or 1e9 pfu)and injected intratumorally in 1-5 intrahepatic tumors on Days 1, 15, and 29.

Study groups in NCT00554372
Study groupRoleWhat they receive
Low DoseExperimental1e8 pfu (plaque forming units) total dose of JX-594 (recombinant vaccinia virus) on each of three (3) treatment days (2 weeks apart)
Receives: Genetic: JX-594: Recombinant vaccinia virus (TK-deletion plus GM-CSF)
High DoseExperimental1e9 pfu (plaque-forming units) total dose of JX-594 (recombinant vaccinia virus) on each of three (3) treatment days (2 weeks apart)
Receives: Genetic: JX-594: Recombinant vaccinia virus (TK-deletion plus GM-CSF)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Proportion of Subjects Achieving Disease Control (Non-progressive Disease) at 8 Weeks After Initiation of Treatment

    Proportion of subjects achieving disease control at 8 weeks based on a modified Response Evaluation Criteria in Solid Tumors v1.0 (mRECIST). Per mRECIST for target lesions as assessed by dynamic contrast enhanced dynamic MRI: Complete Response (CR), Disappearance of all tumor(s); Partial Response (PR), >=30% decrease in the sum of longest diameter (LD) of tumor(s) taking as reference the baseline sum; Stable Disease (SD), any cases that do not qualify for PR or progressive disease (PD); PD, any increase of >= 20% in the sum of longest diameter (LD) of tumor(s) taking as reference the baseline sum. Disease Control (DC) = CR or PR or SD. For mRECIST criteria, new tumor(s) that developed within the liver were measured (a new tumor was defined as a malignant tumor not present at baseline, was ≥ 1 cm in LD had typical hypervascular features of HCC). Their maximum diameter(s) were included in the sum of the maximum diameter; new tumors were not considered evidence for progression.

    Measured: Initial progression status and response assessment at 8 weeks from first dose

Secondary outcomes (3)
  1. Safety and Tolerability of JX-594 Administered at Two Dose Levels

    Treatment-related serious adverse events in patients treated at two dose levels

    Measured: Safety and tolerability were evaluated throughout the 8 week period of study participation

  2. Number of Subjects Achieving Disease Control as Determined Using Intrahepatic Modified RECIST Criteria

    Number of subjects achieving disease control (non-progressive disease) at 8 weeks after treatment was initiated based on modified Response Evaluation Criteria in Solid Tumors for Hepatocellular Carcinoma (mRECIST for HCC). mRECIST for HCC adopted the concept of viable tumor as tumor tissue showing uptake in arterial phase of contrast enhanced radiologic imaging techniques. (see Lencioni and Llovet, Semin. Liver Dis. 2010; 30:52-60). Per mRECIST for HCC, for target lesions as assessed by contrast enhanced dynamic MRI: Complete Response (CR), Disappearance of any intratumoral arterial enhancement in all target (viable) lesions; Partial Response (PR), >=30% decrease in the sum of diameters of viable target lesions; Stable Disease (SD), any cases that do not qualify for PR or progressive disease (PD); PD, any increase of >= 20% in viable target lesions.

    Disease Control (DC) = CR or PR or SD.

    Measured: At week 8

  3. Median Overall Survival

    Overall survival after treatment in days

    Measured: To 760 days post treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Nov 2007 (estimated)
  2. Study startAug 2008
  3. Primary completionDec 2011
  4. Study completionFeb 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
30 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00554372
Sponsor's protocol ID
JX594-IT-HEP007
Status last verified
Jun 2026
First submitted
2 Nov 2007
Last updated
16 Jun 2026
Data monitoring committee
Yes

Publications

  • Heo J, Reid T, Ruo L, Breitbach CJ, Rose S, Bloomston M, Cho M, Lim HY, Chung HC, Kim CW, Burke J, Lencioni R, Hickman T, Moon A, Lee YS, Kim MK, Daneshmand M, Dubois K, Longpre L, Ngo M, Rooney C, Bell JC, Rhee BG, Patt R, Hwang TH, Kirn DH. Randomized dose-finding clinical trial of oncolytic immunotherapeutic vaccinia JX-594 in liver cancer. Nat Med. 2013 Mar;19(3):329-36. doi: 10.1038/nm.3089. Epub 2013 Feb 10.

    PubMed 23396206
  • Breitbach CJ, Arulanandam R, De Silva N, Thorne SH, Patt R, Daneshmand M, Moon A, Ilkow C, Burke J, Hwang TH, Heo J, Cho M, Chen H, Angarita FA, Addison C, McCart JA, Bell JC, Kirn DH. Oncolytic vaccinia virus disrupts tumor-associated vasculature in humans. Cancer Res. 2013 Feb 15;73(4):1265-75. doi: 10.1158/0008-5472.CAN-12-2687. Epub 2013 Feb 7.

    PubMed 23393196

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing JX-594: Recombinant vaccinia virus (TK-deletion plus GM-CSF) in people with Carcinoma, Hepatocellular, run by Jennerex Biotherapeutics at 9 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 16 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in United States, South Korea, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 Aug 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Proportion of Subjects Achieving Disease Control (Non-progressive Disease) at 8 Weeks After Initiation of Treatment (time frame: Initial progression status and response assessment at 8 weeks from first dose). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00554372, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jun 2026.

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