Gene Therapy in Treating Patients With Colon Cancer That Has Spread to the Liver

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Colorectal Cancer, Metastatic Cancer

Intervention / Treatment
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* Biological: NV1020


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: NV1020|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IV colon cancer, recurrent colon cancer, adenocarcinoma of the colon, liver metastases