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.
- 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
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
Patients are followed at 3 months.
PROJECTED ACCRUAL: A total of 12-18 patients will be accrued for this study within 6-12
- 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
- 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
- Over 18
- ECOG 0-1
- More than 3 months
- 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
- 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
- No hepatic insufficiency
- No alcoholic cirrhosis
- Creatinine no greater than 2.0 mg/dL OR
- Creatinine clearance at least 60 mL/min
- No renal insufficiency
- No congestive heart failure
- No serious cardiac arrhythmias
- No evidence of recent prior myocardial infarction on EKG
- No clinical coronary artery disease
- No chronic obstructive pulmonary disease
- 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
- 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:
- 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
- More than 4 weeks since prior chemotherapy and recovered
- At least 4 weeks since prior systemic corticosteroids
- No concurrent systemic corticosteroids
- No concurrent steroids
- See Disease Characteristics
- More than 2 weeks since prior radiotherapy and recovered
- See Disease Characteristics
- More than 4 weeks since prior surgery for primary tumor or metastatic lesions and
- No concurrent immunosuppressive drugs