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

Colorectal Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00012155
• Other study ID #: MSKCC-00022
• Secondary ID: CDR0000068488MGE
• Status: Completed
• Phase: Phase 1
• First received: March 3, 2001
• Last updated: June 25, 2013
• Start date: October 2000
• Est. completion date: December 2009

Study information

• Verified date: November 2002
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Est. completion date: December 2009
• Est. primary completion date: November 2002
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Cancer
• Metastatic Cancer
• Neoplasm Metastasis

Intervention

Biological:
• NV1020

Locations

Country	Name	City	State
United States	Memorial Sloan-Kettering Cancer Center	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

Kemeny N, Jarnagin W, Guilfoyle B, et al.: Results of a phase I, dose-escalating study of the safety, tolerability and anti-tumor activity of a single injection of a genetically engineered herpes simplex virus, nv1020, in subjects with hepatic colorectal