RATIONALE: Vaccines may make the body build an immune response to kill tumor cells. Injecting a vaccine directly into a tumor may cause a stronger immune response and kill more tumor cells.

PURPOSE: This phase II trial is studying how well vaccine therapy works in treating patients with metastatic melanoma.

Condition	Treatment or Intervention	Phase
Stage IV Melanoma Recurrent Melanoma	Drug: fowlpox-TRICOM vaccine  Procedure: biological response modifier therapy  Procedure: recombinant viral vaccine  Procedure: vaccine therapy	Phase II

Further Study Details: 

OBJECTIVES: Primary

• Determine the safety and tolerability of intratumoral fowlpox-TRICOM in patients with metastatic melanoma.
• Determine the local response rate in patients treated with this agent.
• Determine systemic clinical response in patients treated with this agent.

Secondary

• Determine the increase in transgene expression of B7-1, leukocyte function-associated antigen-3 (LFA-3), and intercellular adhesion molecule-1 (ICAM-1) in patients treated with this agent.
• Determine the effects of this agent on CD8-positive antitumor T-cell frequency as measured by ELISpot in these patients.
• Correlate transgene expression of B7-1, LFA-3, and ICAM-1 by tumor cells with changes in function or number of melanoma antigen-specific CD8-positive T lymphocytes in patients treated with this agent.

OUTLINE: This is a multicenter study.

Patients receive fowlpox-TRICOM intratumorally on day 1 of weeks 1, 4, and 7 (maximum of 3 injections for a single lesion) (course 1). After 3 injections (course 1), patients with stable or responding disease receive additional injections into new lesions following the same schedule as above. Treatment repeats every 9 weeks for a maximum total of 9 injections (3 injections total into a maximum of 3 different tumors) (total of 3 courses) in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months until disease progression and then approximately every 6 months for 5-15 years.

PROJECTED ACCRUAL: A total of 14-28 patients will be accrued for this study within 14-28 months.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed melanoma
• Stage IV disease
• Measurable disease
• At least 1 cutaneous or lymph node mass ≥ 1 cm AND amenable to biopsy and percutaneous injection AND can be accurately measured with standard calipers
• HLA-A2 positive
• Must have circulating melanoma-specific CD8-positive T cells against ≥ 1 defined antigen (Melan-A, gp100 antigen, tyrosinase, MAGE-A10, Trp-2, or NA17) by ELISpot technique
• No untreated or edematous brain metastases or leptomeningeal disease
• Treated CNS disease allowed provided patient remains stable off corticosteroid therapy

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• Karnofsky 70-100%

Life expectancy

• More than 12 weeks

Hematopoietic

• WBC ≥ 3,000/mm^3
• Platelet count ≥ 100,000/mm^3
• No uncontrolled bleeding disorder that would increase the risk of bleeding from the injected lesion
• No active thrombotic thrombocytopenic purpura within the past 2 years

Hepatic

• PT/PTT ≤ 1.25 times upper limit of normal (ULN)
• AST and ALT ≤ 1.5 times ULN
• Bilirubin ≤ 1.5 times ULN
• No chronic hepatitis B or C

Renal

• Creatinine ≤ 2.0 mg/dL OR
• Creatinine clearance ≥ 60 mL/min

Cardiovascular

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Immunologic

• HIV negative
• No prior significant allergic reaction or hypersensitivity to eggs or egg products
• No disease that limits the function of the spleen (e.g., sickle cell disease)
• No uncontrolled active or chronic infection
• No active autoimmune disorders or disease
• No immunosuppression, defined as concurrent or possible requirement for systemic corticosteroids

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for at least 4 weeks after study participation
• Able to avoid direct contact of the immunization site with the following individuals:
• Children < 3 years of age
• Immunocompromised individuals (including those on systemic corticosteroids)
• Pregnant women
• Individuals with extensive skin disease
• No active seizure disorder
• No skin disease and/or open unhealing wounds
• No psychiatric illness or social situation that would preclude study compliance
• No other significant medical illness that would significantly increase the risk associated with immunotherapy
• No other active malignancy requiring concurrent therapy except squamous cell or basal cell skin cancer or undetectable hormone-responsive prostate cancer (as measured by normal prostate-specific antigen)
• No other concurrent uncontrolled illness that would preclude study participation

PRIOR CONCURRENT THERAPY: Biologic therapy

• No prior fowlpox virus-based therapy
• No prior B7-1, intercellular adhesion molecule-1 (ICAM-1), or leukocyte function-associated antigen-3 (LFA-3)

Chemotherapy

• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered

Endocrine therapy

• See Disease Characteristics
• Concurrent adjuvant hormonal therapy for early-stage or high-risk breast cancer allowed
• No concurrent corticosteroids

Radiotherapy

• More than 2 weeks since prior radiotherapy and recovered

Surgery

• More than 2 weeks since prior surgery and recovered
• No prior splenectomy

Other

• No concurrent therapeutic anticoagulation therapy that would increase the risk of bleeding from injected lesion
• No other concurrent immunosuppressive drugs
• No other concurrent investigational agents
• No other concurrent anticancer therapy

Illinois
      University of Chicago Cancer Research Center, Chicago,  Illinois,  60637,  United States; Recruiting

Study chairs or principal investigators

Amy Peterson, MD,  Study Chair,  University of Chicago Cancer Research Center   

Study ID Numbers:  CDR0000374979; UCCRC-12759A; NCI-6038; NCT00087373
Record last reviewed:  February 2005
Last Updated:  February 15, 2005
Record first received:  July 8, 2004
ClinicalTrials.gov Identifier:  NCT00087373
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08