Interferon-Beta Gene Transfer (Ad.hIFN-β) as Treatment for Refractory Colorectal Carcinoma With Liver Metastases

Inclusion Criteria: Subjects with histologically confirmed hepatic metastases from primary colorectal carcinoma. Not amenable to complete surgical resection for attempted cure as determined by the Principal Investigator (PI). Tumor progression after prior therapy for colorectal carcinoma, including fluoropyrimidine (5 FU or capecitabine), irinotecan, oxaliplatin, or cetuximab. One or more metastatic hepatic tumors that is measurable on CT scan. In addition, subjects may have nonhepatic metastatic tumors. ECOG performance status of ≤ 1. Age ≥ 18 years. Signed, written IRB-approved informed consent. Men and women of reproductive potential must be willing to follow accepted birth control methods during treatment and for 3 months after completion of treatment. Acceptable liver function: Bilirubin ≤ 1.5 x upper limit of normal; AST, ALT ≤ 2.0 x upper limit of normal; Albumin ≤ 3.0 g/dL. Acceptable hematologic status: Granulocyte ≥ 1000 cells/mm3; Platelet count ≥ 150,000 plts/mm3; Hemoglobin > 9 g/dL. Acceptable coagulation status: INR within normal limits. Acceptable kidney function: Serum creatinine within normal limits. Exclusion Criteria: New York Heart Association Class III or IV cardiac disease, myocardial infarction within the past 6 months prior to Day 1, unstable arrhythmia, or evidence of ischemia on ECG within 14 days prior to Day 1. Seizure disorders requiring anticonvulsant therapy. Severe chronic obstructive pulmonary disease with hypoxemia. Major surgery, other than diagnostic surgery, within 4 weeks prior to Day 1. Active uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy. Pregnant or nursing women. Treatment with radiation therapy, surgery, chemotherapy, or investigational therapy within 1 month prior to study entry. Unwillingness or inability to comply with procedures required in this protocol. Known infection with HIV, hepatitis B, or hepatitis C. Serious nonmalignant disease (e.g., hydronephrosis, liver failure, or other conditions) that could compromise protocol objectives in the opinion of the investigator and/or the sponsor. Clinically significant bleeding event within the last 3 months, unrelated to trauma. More than 50% of liver replaced by tumor (estimated by the PI from CT scan within 14 days of Day 1). Previous treatment with Ad.hIFN-β. Any prior treatment with a gene delivery vector or an adenovirus therapeutic agent.