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.

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

Further Study Details: 

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.

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

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

New York
      Herbert Irving Comprehensive Cancer Center at Columbia University, New York,  New York,  10032,  United States

Study chairs or principal investigators

Howard L. Kaufman, MD,  Study Chair,  Columbia Presbyterian Medical Center   

Study ID Numbers:  CDR0000068831; CPMC-IRB-14387; AECM-01-003; NCI-3353
Record last reviewed:  January 2004
Last Updated:  October 13, 2004
Record first received:  August 10, 2001
ClinicalTrials.gov Identifier:  NCT00022568
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08