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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

Phase 2
18 Years
Not Enrolling
Carcinoma, Hepatocellular

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Trial Information

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

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.

Inclusion Criteria

Inclusion Criteria

- 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

- 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)

Exclusion Criteria:

- 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

- 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

- 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

- Significant immunodeficiency due to underlying illness (e.g. HIV/AIDS) and/or

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To assess whether one of two dose levels of JX-594 is superior in preventing tumor progression in patients with unresectable primary hepatocellular carcinoma

Outcome Time Frame:

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

Safety Issue:


Principal Investigator

David Kirn, MD

Investigator Role:

Study Director

Investigator Affiliation:

Jennerex Biotherapeutics


United States: Food and Drug Administration

Study ID:




Start Date:

August 2008

Completion Date:

February 2013

Related Keywords:

  • Carcinoma, Hepatocellular
  • Jennerex
  • HCC
  • unresectable primary hepatocellular carcinoma
  • hepatocellular carcinoma
  • liver cancer
  • Phase 2
  • oncolytic virus
  • Pexa-Vec
  • Carcinoma
  • Vaccinia
  • Carcinoma, Hepatocellular



Mayo ClinicRochester, Minnesota  55905
Moores UCSD Cancer CenterLa Jolla, California  92093-0658
Billings Clinic Cancer CenterBillings, Montana  59107-5100
The Ohio State UniversityColumbus, Ohio  43210
University of Pittsburgh Medical Center - Liver Cancer CenterPittsburgh, Pennsylvania  15213