Safety and Efficacy of Targeted Gene Transfer in Colorectal Cancer Metastatic to Liver

Inclusion Criteria: Patients will be considered candidates for the proposed protocol if the patients have failed standard chemotherapy regimens (5-FU, LV and CPT-11), in the judgment of the principal investigator, and meet the following criteria:

1. Histologically or cytologically confirmed colorectal carcinoma metastatic to liver, which is unresectable based on the judgment of the patient's surgeon) and is radiologically measurable.
2. Adequate hepatic function: Total bilirubin \< 2.0 mg/dL (upper limit included); AST/ALT \< 2x institutional norm; alkaline phosphatase \< 3x upper limit of institutional norm, albumin \> 3.0 mg/dL. There must be no substantial ascites. PT and PTT must be within normal limits.
3. Performance status must be 0-1 (SWOG 0-1) with a life expectancy of at least 3 months.
4. Absolute granulocyte count \> 1000/uL, and platelet count \> 100,000/uL.
5. Calculated creatinine clearance \> 60ml/hour.
6. There must be no plans for the patient to receive further cancer therapy from the date of enrollment until the completion of the 12 week follow-up visit.
7. Installation of a functional hepatic arterial infusion (HAI) with satisfactory positioning of the catheter in a primary branch of the hepatic artery, placed within the prior 6 months to three weeks. If the patient does not presently have a hepatic artery infusion pump in place, a pump can be placed for them so that they might qualify to participate in the intervention and follow-up phases of this clinical trial.
8. Age \> 18 years, in order to protect children or minors from the potential risks of a new drug that has not yet been tested in adults.
9. The ability to understand and the willingness to sign a written informed -consent document.

Exclusion Criteria

1. Prior malignancy, except for non-melanoma skin cancer, stage I breast cancer, CIS of cervix from which the patient has been disease free for 5 years.
2. Woman who are pregnant or nursing
3. Fertile patients unless they agree to use barrier contraception (condoms and spermicide jelly) during the vector infusion period and for six weeks after infusion.
4. Patients with medical, psychiatric, or social conditions that would compromise successful adherence to this protocol.
5. Patients with indwelling biliary stents or a recent history of cholangitis, hepatitis, presence of disseminated intravascular coagulopathy, or HIV infection. Patients must not have a history of recent myocardial infarction (within one year) or evidence of congestive heart failure.
6. Patients with a history of bleeding varices in the prior 3 months.
7. Patients who have received any other antitumor treatment (chemotherapy, radiation, immunotherapy) within 4 weeks of study entry or who have not recovered from previous therapy or within 6 weeks for mitomycin C and nitrosureas.