gene therapy in treating patients with colon cancer that has spread to the liver

Conditions: Colorectal Cancer; Metastatic Cancer

Summary: 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.

objectives: * determine the safety and maximum tolerated dose of a single intrahepatic nv1020 injection in patients with hepatic metastases from colon cancer that has failed first-line chemotherapy. * 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.

Eligibility 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

Keywords: stage iv colon cancer recurrent colon cancer adenocarcinoma of the colon liver metastases