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

This trial is a clinical research study of Ad.hIFN-β, an investigational, replication-defective, recombinant adenovirus containing the human interferon beta gene, for people that have refractory colorectal carcinoma with liver metastases. Scientists have been exploring a variety of approaches to develop medications to treat patients with refractory colorectal carcinoma with liver metastases; a disease for which current treatment provides only limited relief, so there is a need for new medications.

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.