A Phase I, Open-Label, Dose-Escalating Study Of The Safety, Tolerability, And Anti-Tumor Activity Of A Single Intrahepatic Arterial Injection Of Genetically Engineered Herpes Simplex Virus, NV1020, In Subjects With Adenocarcinoma Of The Colon With Metastasis To The Liver

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically confirmed adenocarcinoma of the colon

- At least 3 metastatic hepatic lesions involving both lobes

- No extrahepatic disease

- Failed first-line combination chemotherapy of fluorouracil plus either leucovorin
calcium or irinotecan

- Herpes simplex virus type-1 seropositive

- Candidate for intrahepatic arterial infusion pump placement

PATIENT CHARACTERISTICS:

Age:

- 18 and over

Performance status:

- Karnofsky 70-100%

Life expectancy:

- Not specified

Hematopoietic:

- WBC greater than 3,000/mm^3

- Absolute neutrophil count greater than 1,500/mm^3

- Platelet count greater than 100,000/mm^3

- Hemoglobin greater than 9.0 g/dL

- No history of any blood clotting disorder (e.g., hemophilia)

Hepatic:

- Transaminases no greater than 3 times upper limit of normal

- Bilirubin no greater than 2.0 mg/dL

- No active hepatitis

- No history of hepatic fibrosis, cirrhosis, or hemochromatosis

Renal:

- Creatinine no greater than 2.0 mg/dL

Other:

- Not pregnant or nursing

- Negative pregnancy test

- All patients must use effective barrier contraception during and for at least 6
months after study

- HIV negative

- No active herpes infection

- No other active uncontrolled infection

- No prior weight loss of more than 10 lbs within the past month

- No history of alcohol or other substance abuse

- No concurrent unstable and/or severe medical or psychological condition

- No history of any other medical or psychological condition that would preclude study

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- At least 4 weeks since prior immunotherapy (e.g., interleukin-2, interleukin -12, or
interferon)

- No prior gene transfer therapy

- No prior therapy with cytolytic virus of any type

- No concurrent immunotherapy during and for 28 days after study therapy

- No concurrent vaccines during and for 28 days after study therapy

Chemotherapy:

- See Disease Characteristics

- At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)

- No concurrent chemotherapy during and for 28 days after study therapy

Endocrine therapy:

- No concurrent systemic steroids during and for 28 days after study therapy

Radiotherapy:

- No prior radiotherapy to the liver

- No concurrent radiotherapy during and for 28 days after study therapy

Surgery:

- At least 2 weeks since prior surgery

Other:

- At least 30 days since prior participation in investigational study

- No concurrent antiviral agent active against herpes simplex virus (e.g., acyclovir,
valacyclovir, penciclovir, famciclovir, ganciclovir, foscarnet, or cidofovir) during
and for 28 days after study therapy

- No concurrent immunosuppressive agents (e.g., cyclosporine) during and for 28 days
after study therapy

- No other concurrent investigational or anti-cancer agents during and for 28 days
after study therapy