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.

Condition	Treatment or Intervention	Phase
recurrent colon cancer liver metastases stage IV colon cancer adenocarcinoma of the colon	Procedure: gene therapy  Drug: NV1020	Phase I

Further Study Details: 

OBJECTIVES: I. 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. II. Determine the tolerability of this drug in these patients. III. Determine preliminarily the anti-tumor activity of this drug in these patients. IV. Assess the immunogenicity of NV1020 in these patients.

PROTOCOL 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.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY 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

--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

--Patient Characteristics--

Age: 18 and over

Performance status: Karnofsky 70-100%

Life expectancy: Not specified

Hematopoietic:

• WBC greater than 3,000/mm3
• Absolute neutrophil count greater than 1,500/mm3
• Platelet count greater than 100,000/mm3
• 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

New York
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States

Study chairs or principal investigators

Yuman Fong,  Study Chair,  Memorial Sloan-Kettering Cancer Center   

Study ID Numbers:  CDR0000068488; MSKCC-00022; NCI-G01-1920; MGENE-NR1-001
Record last reviewed:  June 2003
Last Updated:  October 13, 2004
Record first received:  March 3, 2001
ClinicalTrials.gov Identifier:  NCT00012155
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08