Colorectal Cancer, Metastatic Cancer
Conditions
Keywords
stage IV colon cancer, recurrent colon cancer, adenocarcinoma of the colon, liver metastases
Brief 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.
Detailed description
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.
Interventions
BIOLOGICALNV1020
Sponsors
National Cancer Institute (NCI)
Memorial Sloan Kettering Cancer Center
Study design
Primary purpose
TREATMENT
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Countries
United States
Outcome results
None listed