A Study of Recombinant Vaccinia Virus to Evaluate the Safety and Efficacy of a Transdermal Injection Within the Tumor of Patients With Primary or Metastatic Hepatic Carcinoma

Phase 1 Clinical Study for Evaluating the Safety and Efficacy of a Transdermal Injection of JX-594 (Thymidine Kinase (-)/GM-CSF(+) Vaccinia Virus) Within the Tumor of Patients With Hepatic Carcinoma

The primary purpose of this study is to determine the maximum tolerable dose (MTD) and/or the maximum feasible dose (MFD), as well as to evaluate the safety of JX-594 (Pexa-Vec) injected within hepatic carcinoma tumors.

Patients are treated with JX-594 once every three weeks until progression at the site(s) of injection or until the patient has received a maximum of 4 treatments; four additional cycles can be administered to patients with an objective response of the injected tumor(s) (i.e. 8 total treatments possible). Study dose levels are 1e8 pfu, 3e8 pfu, 1e9 pfu and 3e9 pfu per treatment. Standard Phase I dose-escalation guidelines are used, with 2-6 patients enrolled per cohort (3 if no dose-limiting toxicities are reported).

Inclusion Criteria:

• Age ≥ 18 years
• Patients with hepatic carcinoma (primary or metastatic) clinically or histologically confirmed to have tumors (≤10cm maximum diameter) that are progressing (refractory to standard treatment) despite regular treatment and that can be transdermally accessed by an injection needle in an imaging-guided procedure
• Tumor progression despite undergoing regular treatment such as surgery, transarterial chemoembolization, chemotherapy, and radiotherapy
• Performance score: Karnofsky Performance Score (KPS) ≥70
• Expected survival of at least 16 weeks
• For patients who are sexually active, able and willing to use contraceptives for a three month period during and after taking JX-594
• WBC > 3,500 cells/mm3
• ANC > 1,500 cells/mm3
• Hemoglobin > 10g/dL
• Platelet count > 75,000 plts/mm3
• Serum creatinine < 1.5 mg/dL
• AST, ALT < 2.5 x ULN
• Total bilirubin ≤ 2.0 mg/dL
• In patients with primary HCC, Child Pugh A or B
• Able/willing to sign an IRB/IEC/REB-approved written consent form
• Able and willing to comply with study procedures and follow-up examinations

Exclusion Criteria:

• 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)
• Patients with household contacts with significant immunodeficiency
• History of exfoliative skin condition (e.g. severe eczema, ectopic dermatitis, or similar skin disorder) that at some stage has required systemic therapy
• Severe or unstable cardiac disease
• Use of adrenal cortical hormone drug or immunosuppressant within four weeks of study enrollment