A Study of Recombinant Vaccinia Virus to Treat Unresectable Primary Hepatocellular Carcinoma
Condition: Carcinoma, Hepatocellular
MeSH terms: Vaccinia; Carcinoma; Carcinoma, Hepatocellular
Intervention: JX-594: Recombinant vaccinia virus (TK-deletion plus GM-CSF)
Intervention description: 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.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 30.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Jennerex; HCC; unresectable primary hepatocellular carcinoma; hepatocellular carcinoma; liver cancer; Phase 2; oncolytic virus; Pexa-Vec

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.
    

Eligibility 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
             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