Vaccine Therapy in Treating Patients With Metastatic Melanoma

Study Overview
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Brief Summary
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RATIONALE: Vaccines may make the body build an immune response to kill tumor cells. Interleukin-2 may stimulate a person's white blood cells to kill tumor cells. PURPOSE: Randomized phase II trial to study the effectiveness of vaccine therapy with and without interleukin-2 in treating patients who have metastatic melanoma that has not responded to previous treatment.

Detailed Description
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OBJECTIVES: Determine efficacy of recombinant fowlpox and vaccinia viruses encoding tyrosinase antigen, administered with or without low-dose interleukin-2 (IL-2), in terms of response, in patients with metastatic melanoma. Compare the response rate in patients to this vaccination administered with high-dose IL-2 to that in similar patients on previous trials treated with high-dose IL-2 alone. Determine the immunological response in patients treated with this regimen. OUTLINE: This is a randomized study. Patients are randomized to one of three treatment arms. Arm I: Patients receive recombinant fowlpox vaccine IM on day 1 followed 4 weeks later by recombinant vaccinia vaccine IM. Treatment repeats for a minimum of 4 vaccinations. Arm II: Patients receive vaccinations as in arm I plus low-dose interleukin-2 (IL-2) subcutaneously daily on days 2-13 after each vaccination. Arm III: Patients receive vaccinations as in arm I plus high-dose IL-2 IV over 15 minutes every 8 hours on days 2-5 after each vaccination. Patients with stable disease or a minor, mixed, or partial response after four immunizations (1 course) may receive a second course of the same regimen beginning 4-6 weeks after the first course. After the second course, patients with tumor regression may continue to receive treatment in the absence of unacceptable toxicity until best response is achieved. Patients are followed at 4-6 weeks. PROJECTED ACCRUAL: A total of 73 patients (13-20 for arm I, 13-20 for arm II, and 19-33 for arm III) will be accrued for this study within 2 years.

Official Title
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Immunization of Patients With Metastatic Melanoma Using Recombinant Fowlpox and Vaccinia Viruses Encoding the Tyrosinase Antigen

Conditions
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Melanoma (Skin)

Intervention / Treatment
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* Biological: aldesleukin
* Biological: fowlpox virus vaccine vector
* Biological: vaccinia-tyrosinase vaccine


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed metastatic melanoma that has failed standard treatment No ocular or mucosal melanoma as primary site Measurable disease No existing brain metastases PATIENT CHARACTERISTICS: Age: 16 and over Performance status: ECOG 0 or 1 Life expectancy: More than 3 months Hematopoietic: WBC at least 3,000/mm3 Platelet count at least 90,000/mm3 No coagulation disorder Hepatic: Bilirubin no greater than 1.6 mg/dL AST/ALT less than 3 times normal Hepatitis B surface antigen negative Renal: Creatinine no greater than 1.6 mg/dL Cardiovascular: No major cardiovascular illness Pulmonary: No major respiratory illness Immunologic: HIV negative No autoimmune disease No primary or secondary immunodeficiency No allergy to eggs No history of allergy or untoward reaction to prior smallpox vaccination Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Must be able to avoid close contact with children under 5 years, pregnant women, people with active or a past history of eczema or other eczematoid skin disorders, and immunosuppressed people for at least 2 weeks after each vaccinia virus vaccination No active systemic infections No active atopic dermatitis or active or past history of eczema No concurrent active extensive psoriasis, severe acneiform rash, impetigo, varicella zoster, burns, or other traumatic or pruritic skin conditions or open wounds Surgical scars must be healed Healed surgical stomas (e.g., colostomy) allowed PRIOR CONCURRENT THERAPY: Biologic therapy: No prior recombinant vaccinia or fowlpox vaccines for melanoma At least 3 weeks since prior systemic biologic therapy for melanoma Chemotherapy: At least 3 weeks since prior systemic chemotherapy for melanoma Endocrine therapy: At least 3 weeks since prior systemic endocrine therapy for melanoma No concurrent steroid therapy Radiotherapy: At least 3 weeks since prior systemic radiotherapy for melanoma Surgery: Prior surgery allowed

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: aldesleukin|nan|
|Biological: fowlpox virus vaccine vector|nan|
|Biological: vaccinia-tyrosinase vaccine|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IV melanoma, recurrent melanoma