vaccine therapy in treating patients with metastatic melanoma

Conditions: Melanoma (Skin)

Summary: rationale: vaccines may make the body build an immune response to kill tumor cells. purpose: phase i trial to study the effectiveness of vaccine therapy in treating patients who have metastatic melanoma.

objectives: * determine the maximum tolerated dose of recombinant vaccinia-tricom vaccine in patients with metastatic melanoma. * determine the clinical toxic effects of this vaccine in these patients. * determine the safety of this vaccine in these patients. * determine the clinical response of these patients to this vaccine. * determine evidence of host anti-melanoma immune reactivity in these patients after treatment with this vaccine. outline: this is a dose-escalation study. patients receive recombinant vaccinia-tricom vaccine once every 4 weeks for a total of 3 vaccinations. patients with stable or responding disease may receive an additional course of vaccinations. cohorts of 3-6 patients receive escalating doses of recombinant vaccinia-tricom vaccine 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 toxicity. quality of life is assessed at baseline, at each vaccine administration, and at study completion. patients are followed at 3 months. projected accrual: a total of 12-18 patients will be accrued for this study within 6-12 months.

Eligibility criteria:
disease characteristics: * histologically confirmed metastatic non-resectable cutaneous, subcutaneous, or lymph node malignant melanoma * lesion(s) must be accessible to percutaneous injection * measurable lesion(s) * at least 1.0 cm * previously treated brain metastases with no evidence of disease or edema on mri or ct scan allowed * at least 6 weeks since prior definitive therapy (surgery or radiotherapy) * no untreated or edematous metastatic brain lesions or leptomeningeal disease * no ascites or pleural effusions patient characteristics: age: * over 18 performance status: * ecog 0-1 life expectancy: * more than 3 months hematopoietic: * wbc at least 3,000/mm3 * platelet count at least 100,000/mm3 * absolute granulocyte count at least 3,000/mm3 * hemoglobin at least 10 g/dl hepatic: * direct bilirubin no greater than 1.5 mg/dl * transaminases no greater than 2 times upper limit of normal (uln) * alkaline phosphatase no greater than 2 times uln * no severe coagulation disorder with pt/ptt greater than 2 times normal (without anticoagulation medications) * no hepatic insufficiency * no alcoholic cirrhosis renal: * creatinine no greater than 2.0 mg/dl or * creatinine clearance at least 60 ml/min * no renal insufficiency cardiovascular: * no congestive heart failure * no serious cardiac arrhythmias * no evidence of recent prior myocardial infarction on ekg * no clinical coronary artery disease pulmonary: * no chronic obstructive pulmonary disease immunologic: * no prior eczema * hiv negative * no immunocompromising conditions, (e.g., active autoimmune disease, leukemia, lymphoma, skin diseases, or open wounds) * no clinical or laboratory evidence of an underlying immunosuppressive disorder * no active or chronic infections * no significant allergy or hypersensitivity to eggs other: * no active seizure disorders * no other malignancy within the past 2 years except stage i cervical cancer or basal cell skin cancer, provided the tumor has been successfully treated and patient is currently disease free * no evidence of bone marrow toxicity * no other concurrent medical illness that would preclude study * no other contraindications to vaccinia virus administration * no encephalitis * must be able to avoid close contact with children under 3 years of age; pregnant women; individuals with prior or active eczema or other open skin conditions; or immunosuppressed individuals for 7-10 days after each vaccination * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception prior concurrent therapy: biologic therapy: * prior vaccinia immunization required (e.g., smallpox vaccination) * more than 8 weeks since prior immunotherapy and recovered * no prior therapy with live vaccinia virus vector chemotherapy: * more than 4 weeks since prior chemotherapy and recovered endocrine therapy: * at least 4 weeks since prior systemic corticosteroids * no concurrent systemic corticosteroids * no concurrent steroids radiotherapy: * see disease characteristics * more than 2 weeks since prior radiotherapy and recovered surgery: * see disease characteristics * more than 4 weeks since prior surgery for primary tumor or metastatic lesions and recovered other: * no concurrent immunosuppressive drugs

Keywords: stage iv melanoma recurrent melanoma