RATIONALE: Gene therapy may make the body build an immune response to kill tumor cells.
PURPOSE: Phase I trial to study the safety of NV1020 in patients who have colon cancer that
has spread to the liver and has not responded to previous chemotherapy.
- Determine the safety and maximum tolerated dose of a single intrahepatic NV1020
injection in patients with hepatic metastases from colon cancer that has failed
- Determine the tolerability of this drug in these patients.
- Determine preliminarily the anti-tumor activity of this drug in these patients.
- Assess the immunogenicity of NV1020 in these patients.
OUTLINE: This is a dose escalation study.
Patients receive a single intrahepatic arterial injection of NV1020 over 10 minutes with the
aid of hepatic arteriography.
Cohorts of 3 patients receive escalating doses of NV1020 until the maximum tolerated dose
(MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 patients
experience dose-limiting toxicity.
Patients are followed at 1, 2, and 3 months post injection. Patients may participate in a
separate long term (up to 1 year) follow-up study for continued assessment and monitoring.
PROJECTED ACCRUAL: A total of 27 patients will be accrued for this study.
- 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
- 18 and over
- Karnofsky 70-100%
- Not specified
- 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)
- 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
- Creatinine no greater than 2.0 mg/dL
- 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:
- At least 4 weeks since prior immunotherapy (e.g., interleukin-2, interleukin -12, or
- 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
- 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
- No concurrent systemic steroids during and for 28 days after study therapy
- No prior radiotherapy to the liver
- No concurrent radiotherapy during and for 28 days after study therapy
- At least 2 weeks since prior surgery
- 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