Gene Therapy and Ganciclovir in Treating Patients With Stage IV Melanoma

NCT ID: NCT00005057

Last Updated: 2015-04-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 2000-03-31

Brief Summary

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.

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.

Conditions

Melanoma (Skin)

Study Design

• Primary Study Purpose: TREATMENT

Interventions

adenovirus RSV-TK

Intervention Type: BIOLOGICAL

ganciclovir

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

National Human Genome Research Institute (NHGRI)

NIH

Sponsor Role: lead

Principal Investigators

John C. Morris, MD

Role: STUDY_CHAIR

NCI - Metabolism Branch;MET

Locations

Clinical Genetherapy Branch

Bethesda, Maryland, United States

Metabolism Branch

Bethesda, Maryland, United States

Baylor College of Medicine

Houston, Texas, United States

Countries

United States

Other Identifiers

NCI-98-C-0140C

Identifier Type: -

Identifier Source: secondary_id

CDR0000067654

Identifier Type: -

Identifier Source: org_study_id

NCT00001755

Identifier Type: -

Identifier Source: nct_alias

NCT00001974

Identifier Type: -

Identifier Source: nct_alias