Oncolytic HSV-1 rRp450 in Treating Patients with Primary Liver Cancer or Liver Metastases

Inclusion Criteria

• Able to understand and sign a written informed consent form
• Histologically confirmed diagnosis of cancer with liver metastases, or histologically confirmed primary liver cancer (e.g. hepatocellular carcinoma, cholangiocarcinoma, or gallbladder carcinoma); subjects may have extrahepatic spread of malignancy, except they may not have brain metastases; subjects with a history of more than one invasive malignancy remain eligible for this study, but in these instances, a liver biopsy is required to document the histology of the liver tumor; an exception to this criterion is made for basal cell carcinoma
• Subjects must have measurable primary or metastatic liver malignancies and have no standard, Food and Drug Administration (FDA)-approved therapy options available
• No liver surgery (including radiofrequency or microwave ablation), chemotherapy (including bevacizumab), immunotherapy, or liver radiotherapy within 4 weeks of enrollment in this clinical trial
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2 and life expectancy greater than 12 weeks based on the investigator's clinical judgment
• White blood cell count (WBC) > 3,000/mm^3
• Absolute neutrophil count (ANC) > 1,500/mm^3
• Platelets > 100,000/mm^3
• Hemoglobin (Hgb) > 9 g/dL
• Prothrombin time (PT)/partial thromboplastin time (PTT) =< 1.4 times upper limit of normal range
• Serum creatinine < 1.8 mg/dL
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 times upper limit of normal
• Total bilirubin =< 1.5 times upper limit of normal range
• Tumor volume occupies less than 50% of liver by volume as assessed by computed tomography (CT) scan or magnetic resonance imaging (MRI) scan within 4 weeks of treatment
• Negative pregnancy test (serum or urine) in premenopausal women

Exclusion Criteria

• Clinical or pathological diagnosis of cirrhosis, hemochromatosis, or hepatic fibrosis
• Diffuse ascites, or complete occlusion of main portal vein
• Hepatitis C infection, chronic infection with hepatitis B, infection with human immunodeficiency virus (HIV), or evidence of hepatic insufficiency
• Inability to practice contraception with condoms as prescribed by the protocol
• Active infection requiring treatment with systemic antibiotics or systemic anti-fungal agents
• Under active treatment with immunosuppressive agents such as systemic corticosteroids or cyclosporine that cannot be discontinued before starting rRp450 infusions
• Unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia, or need for antiarrhythmic medication for which inability to take an oral preparation of regular medication for 48 hours would represent an unacceptable risk
• Known existing uncontrolled coagulopathy, hemorraghic disorder, or inability to discontinue anticoagulants prior to each treatment (except for prophylaxis against portacath-associated thrombosis, which does not require cessation of therapy)
• History of seizures
• Allergy to acyclovir or inability to receive contrast for CT and MRI scans
• Prior liver resection of greater than 5 anatomic segments as defined by Couinaud; (subjects that have undergone prior liver wedge excisions or segmental resections are not excluded on this basis alone)