Vaccine Therapy in Treating Patients With Unresectable Metastatic Melanoma

Study Overview
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Brief Summary
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Phase I trial to study the effectiveness of vaccine therapy in treating patients who have unresectable metastatic melanoma. Vaccines may make the body build an immune response to kill tumor cells.

Detailed Description
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OBJECTIVES: I. Determine the maximum tolerated dose of the rV-B7.1 vaccine that elicits a host immune response and is associated with acceptable toxicity in patients with malignant metastatic melanoma. II. Determine all clinical toxicities associated with this regimen in this patient population. III. Determine the safety of this regimen in this patient population. IV. Assess evidence of host antimelanoma immune reactivity following this regimen. V. Determine the effect of this regimen on T-cell immunity. VI. Assess the clinical response in this patient population receiving this regimen. VII. Evaluate quality of life of these patients during this regimen. OUTLINE: This is a dose escalation study. Patients receive rV-B7.1 intralesionally every 4 weeks for 8 weeks (weeks 0, 4, and 8). Treatment continues every 12 weeks in the absence of unacceptable toxicity or disease progression for up to 2 courses. Cohorts of 6-8 patients receive escalating doses of vaccine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 or 3 of 8 patients experience dose limiting toxicities. Quality of life is assessed before treatment, every 4 weeks, and at end of treatment. Patients are followed every 3 months.

Official Title
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A Phase I Trial of Intra Lesional RV-B7.1 Vaccine in the Treatment of Malignant Melanoma

Conditions
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Melanoma (Skin)

Intervention / Treatment
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* Biological: recombinant vaccinia-B7.1 vaccine


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically proven metastatic, unresectable melanoma Dermal, subcutaneous, or lymph node metastases Accessible for injection Lesions must measure at least 1 cm Patients with no prior treatment allowed Patients must have one of the following as proof of prior vaccinia immunization: Physician certification Recollection and appropriate vaccination scar site No encephalitis, untreated cerebral metastases, other structural brain lesions, or leptomeningeal disease No ascites or pleural effusions No leukemia or lymphoma PATIENT CHARACTERISTICS: Age: Over 18 Performance status: ECOG 0-1 Karnofsky 80-100% Life expectancy: Greater than 3 months WBC greater than 4,000/mm3 Platelet count greater than 100,000/mm3 Hemoglobin greater than 10g/dL Bilirubin less than 1.5 mg/dL Transaminases no greater than 2 times upper limit of normal (ULN) Alkaline phosphatase no greater than 2 times ULN PT/PTT no greater than 2 fold elevation in patients not receiving anticoagulation medications No alcoholic cirrhosis Creatinine less than 2.0 mg/dL OR creatine clearance greater than 60 mL/min No congestive heart failure No serious cardiac arrhythmias No recent prior myocardial infarction No clinical coronary artery disease No chronic obstructive pulmonary disease Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No seizure disorders No underlying immunosuppressive disorder No autoimmune disease HIV negative No skin diseases No open wounds No eczema or other contraindications to vaccinia virus administration Patients must be able to avoid high risk individuals (e.g., immunosuppressed patients, children under 3 years, pregnant women, patients with active or a history of eczema, or patients with other skin conditions) for 7-10 days following treatment No significant allergy or hypersensitivity to eggs No active or chronic infections No concurrent medical illness No other significant medical disease which would increase risk to patient No other prior malignancy within the past 5 years except stage I carcinoma of the cervix or basal cell carcinoma PRIOR CONCURRENT THERAPY: At least 8 weeks since prior immunotherapy and recovered No prior live pox virus vector No more than 2 prior chemotherapy regimens At least 4 weeks since prior chemotherapy and recovered At least 4 weeks since prior systemic corticosteroids No systemic corticosteroids for concurrent illness No concurrent immunosuppressive steroids At least 2 weeks since prior radiotherapy and recovered (no bone marrow toxicity) At least 6 months since prior radiotherapy for brain metastases and recovered At least 4 weeks since prior surgery for management of the primary or metastatic lesions and recovered with remaining measurable disease At least 6 months since prior surgery for brain metastases and recovered No concurrent immunosuppressive drugs

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>Patients receive rV-B7.1 intralesionally every 4 weeks for 8 weeks (weeks 0, 4, and 8). Treatment continues every 12 weeks in the absence of unacceptable toxicity or disease progression for up to 2 courses. Cohorts of 6-8 patients receive escalating doses of vaccine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 or 3 of 8 patients experience dose limiting toxicities. | Biological: recombinant vaccinia-B7.1 vaccine<br> <br> |

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 III melanoma, stage IV melanoma, recurrent melanoma