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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.
Studie Overzicht
Toestand
Conditie
Interventie / Behandeling
Gedetailleerde beschrijving
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.
Studietype
Fase
- Fase 1
Contacten en locaties
Studie Locaties
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New York
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New York, New York, Verenigde Staten, 10021
- Memorial Sloan-Kettering Cancer Center
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Deelname Criteria
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
Accepteert gezonde vrijwilligers
Geslachten die in aanmerking komen voor studie
Beschrijving
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
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
Medewerkers en onderzoekers
Medewerkers
Onderzoekers
- Studie stoel: Yuman Fong, MD, Memorial Sloan Kettering Cancer Center
Publicaties en nuttige links
Algemene publicaties
- 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.
Studie record data
Bestudeer belangrijke data
Studie start
Primaire voltooiing (Werkelijk)
Studie voltooiing (Werkelijk)
Studieregistratiedata
Eerst ingediend
Eerst ingediend dat voldeed aan de QC-criteria
Eerst geplaatst (Schatting)
Updates van studierecords
Laatste update geplaatst (Schatting)
Laatste update ingediend die voldeed aan QC-criteria
Laatst geverifieerd
Meer informatie
Termen gerelateerd aan deze studie
Trefwoorden
Aanvullende relevante MeSH-voorwaarden
Andere studie-ID-nummers
- MSKCC-00022
- CDR0000068488 (Register-ID: PDQ (Physician Data Query))
- MGENE-NR1-001
- NCI-G01-1920
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