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

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 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