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

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

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.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer; Metastatic Cancer
• Intervention / Treatment: Biological: NV1020

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.

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Yuman Fong, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

General Publications

• 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 metastases. [Abstract] Ann Oncol 16 (Suppl 2): A-480, ii283, 2005.

Study record dates

Study Major Dates

• Study Start: October 1, 2000
• Primary Completion (Actual): November 1, 2002
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: March 3, 2001
• First Submitted That Met QC Criteria: June 6, 2003
• First Posted (Estimate): June 9, 2003

Study Record Updates

• Last Update Posted (Estimate): June 26, 2013
• Last Update Submitted That Met QC Criteria: June 25, 2013
• Last Verified: November 1, 2002

More Information

Terms related to this study

• Keywords: stage IV colon cancer; adenocarcinoma of the colon; recurrent colon cancer; liver metastases
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Neoplasm Metastasis
• Other Study ID Numbers: MSKCC-00022; CDR0000068488 (Registry Identifier: PDQ (Physician Data Query)); MGENE-NR1-001; NCI-G01-1920