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Gene Therapy and Ganciclovir in Treating Patients With Stage IV Melanoma
This study has been completed.
First Received: April 6, 2000   Last Updated: February 6, 2009   History of Changes
Sponsors and Collaborators: National Human Genome Research Institute (NHGRI)
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00005057
  Purpose

RATIONALE: Inserting a modified herpesvirus gene into a person's melanoma cells may make the cancer more sensitive to the antiviral agent ganciclovir.

PURPOSE: Phase I trial to study the effectiveness of gene therapy in treating patients who have stage IV melanoma.


Condition Intervention Phase
Melanoma (Skin)
Biological: adenovirus RSV-TK
Drug: ganciclovir
Phase I

MedlinePlus related topics: Cancer Melanoma
Drug Information available for: Ganciclovir Ganciclovir sodium
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment
Official Title: A Phase I Study of Intralesional Administration of an Adenovirus Vector Expressing the HSV-1 Thymidine Kinase Gene (AdV.RSV-TK) in Combination With Escalating Doses of Ganciclovir in Patients With Cutaneous Metastatic Malignant Melanoma

Further study details as provided by National Cancer Institute (NCI):

Study Start Date: March 2000
Detailed Description:

OBJECTIVES: I. Determine the maximum tolerated dose of ganciclovir administered IV every 12 hours for 7 days in combination with adenovirus RSV-TK administered by direct intralesional injection in patients with cutaneous or subcutaneous metastatic malignant melanoma. II. Determine the dose limiting toxicities of this regimen in this patient population. III. Evaluate the response (both local and at distant metastatic sites), duration of response, response by ganciclovir dose, and any impact local treatment with adenovirus RSV-TK and ganciclovir "suicide" gene therapy may have on overall survival in these patients.

OUTLINE: This is a dose escalation study of ganciclovir. Patients are stratified according to response of the index lesion and other metastatic disease sites. Patients receive an intratumoral injection of adenovirus RSV-TK on day 1. Ganciclovir IV is administered every 12 hours on days 3-10 for a total of 14 doses. Patients sustaining a partial response (PR) or complete response (CR) may be retreated 2 weeks after documented PR or CR. Cohorts of 3-6 patients receive escalating doses of ganciclovir until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose limiting toxicities. Patients are followed at 3 weeks, 4 weeks, 60 days, then every 2 months for 6 months, and then every 3 months for 1.5 years.

PROJECTED ACCRUAL: A maximum of 27 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS: Histologically confirmed advanced stage IV malignant melanoma M1 All pathologic subtypes eligible Tridimensionally measurable disease At least 1 discreet easily accessible and measurable cutaneous or subcutaneous lesion of a volume no greater than 3 cm3 by physical examination using Vernier calipers Ulcerated or necrotic lesions may not serve as index lesion Not a candidate for curative surgical resection Visceral metastases, including brain lesions, eligible provided no rapidly progressive CNS metastases likely to result in death within 3 months

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 60-100% Life expectancy: Greater than 3 months Hematopoietic: Absolute neutrophil count at least 1,800/mm3 Platelet count at least 100,000/mm3 Hemoglobin at least 9.0 g/dL Hepatic: BUN no greater than 1.5 times upper limit of normal (ULN) Bilirubin no greater than 1.5 times ULN Renal: Creatinine no greater than 1.8 mg/dL OR Creatinine clearance at least 70 mL/min Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 3 months after study No other clinically significant medical disease that is poorly controlled and/or expected to impact patient survival or that would preclude study therapy No significant cognitive impairment No serious active infection requiring intravenous antibiotic or antiviral therapy No clinical AIDS No primary immunodeficiencies No other concurrent active malignancy No history of sensitivity to ganciclovir or other antiviral drugs of this family No prior severe reaction to adenovirus or herpes virus infection (e.g., toxic epidermal necrolysis or Stevens-Johnson syndrome)

PRIOR CONCURRENT THERAPY: Biologic therapy: At least 4 weeks since prior biological response modifier therapy (e.g., interleukin-2, interferon) and recovered No prior gene therapy using adenoviral based vectors, chimeric adenoviral based vectors, HSV-tk or other thymidine kinase based therapy No concurrent biological response modifier therapy No other concurrent gene therapy including ribozyme and antisense based therapy Chemotherapy: At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas, melphalan, or mitomycin) and recovered No concurrent antineoplastic chemotherapy Endocrine therapy: Concurrent replacement or therapeutic corticosteroids allowed Radiotherapy: Prior radiotherapy allowed provided index lesion not within radiation field Recovered from prior radiotherapy No concurrent radiotherapy except for CNS metastases provided index lesion not within radiation field Surgery: See Disease Characteristics Recovered from prior surgery Other: No other concurrent ganciclovir, acyclovir, or similar antiviral drug No concurrent immunosuppressive therapy (e.g., organ allograft)

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00005057

Locations
United States, Maryland
Clinical Genetherapy Branch
Bethesda, Maryland, United States, 20892
Metabolism Branch
Bethesda, Maryland, United States, 20892
United States, Texas
Baylor College of Medicine
Houston, Texas, United States, 77030
Sponsors and Collaborators
Investigators
Study Chair: John C. Morris, MD NCI - Metabolism Branch;MET
  More Information

Additional Information:
No publications provided

Study ID Numbers: CDR0000067654, NCI-98-C-0140C
Study First Received: April 6, 2000
Last Updated: February 6, 2009
ClinicalTrials.gov Identifier: NCT00005057     History of Changes
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
stage IV melanoma
recurrent melanoma
lentigo maligna malignant melanoma
superficial spreading malignant melanoma
acral lentiginous malignant melanoma
nodular malignant melanoma

Study placed in the following topic categories:
Hutchinson's Melanotic Freckle
Lentigo
Adenoviridae Infections
Ganciclovir
Antiviral Agents
Lentigo Maligna Melanoma
Recurrence
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Nevus, Pigmented
Neuroepithelioma
Nevus

Additional relevant MeSH terms:
Anti-Infective Agents
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Ganciclovir
Antiviral Agents
Pharmacologic Actions
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms
Neoplasms, Germ Cell and Embryonal
Therapeutic Uses
Nevi and Melanomas

ClinicalTrials.gov processed this record on May 07, 2009