RATIONALE: Vaccines may make the body build an immune response to and kill melanoma cells. PURPOSE: Phase I/II trial to study the effectiveness of vaccine therapy in treating patients with metastatic melanoma.

Condition	Treatment or Intervention	Phase
stage III melanoma Stage IV Melanoma Recurrent Melanoma	Procedure: biological response modifier therapy  Procedure: colony-stimulating factor therapy  Procedure: cytokine therapy  Procedure: vaccine therapy  Vaccine: recombinant viral vaccine  Drug: sargramostim	Phase I Phase II

Further Study Details: 

OBJECTIVES: I. Determine the toxicity of intralesional immunotherapy with a recombinant vaccinia virus encoding the gene for sargramostim (GM-CSF) in patients with metastatic melanoma. II. Determine the efficiency of viral infection and GM-CSF gene insertion and function in these patients. III. Determine the capacity of this regimen to generate antiviral and antitumor immunity in these patients. IV. Determine the frequency of regression of injected and uninjected lesions in these patients.

PROTOCOL OUTLINE: This is a dose escalation study of intralesional recombinant vaccinia virus encoding the gene for sargramostim (GM-CSF) (recombinant vaccinia/GM-CSF vaccine). Patients are stratified by center. Patients receive small pox (vaccinia) vaccine via multipuncture technique on day 0. On day 4, patients with a major reaction in progress to the initial vaccination receive recombinant vaccinia/GM-CSF vaccine intralesionally twice weekly for 5 weeks. Only 1 lesion is treated and at least 1 measurable lesion is left untreated in each patient. Intrapatient dose escalation occurs each week. Patients with responding disease after week 5 are retreated at a clinically appropriate dose and schedule. Cohorts of 5 patients receive escalating doses of intralesional recombinant vaccinia/GM-CSF vaccine until the maximum tolerated dose (MTD) is determined. Additional patients receive vaccine at the MTD.

PROJECTED ACCRUAL: Approximately 15 patients will be accrued for phase I and a total of 15 patients will be accrued for phase II of the study.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically proven melanoma that is considered surgically incurable
• Dermal, subcutaneous, or lymph node metastases required; At least 3 lesions evaluable and accessible for injection and biopsy; One lesion at least 10 mm in diameter

--Prior/Concurrent Therapy--

• Biologic therapy: Not specified
• Chemotherapy: At least 8 weeks since prior chemotherapy
• Endocrine therapy: No concurrent or imminent steroid therapy
• Radiotherapy: At least 8 weeks since prior radiotherapy
• Surgery: At least 4 weeks since prior surgery

--Patient Characteristics--

• Age: 18 and over
• Performance status: ECOG 0-1
• Life expectancy: At least 6 months
• Hematopoietic: Not specified
• Hepatic: Bilirubin no greater than 3 times upper limit of normal (ULN); SGOT no greater than 3 times ULN; Alkaline phosphatase no greater than 3 times ULN
• Renal: Creatinine no greater than 3 times ULN
• Immunologic: Clinical evidence of immune response required within 4 days of smallpox vaccination; At least 1 positive cutaneous delayed-type hypersensitivity response to 1 of the following: Microbial recall antigens; Dinitrofluorobenzene after sensitization; Purified protein derivative of tuberculin following BCG vaccination; No altered immunocompetence (e.g., immune deficiency disease or immunosuppressive therapy) in patient or household contacts; No allergy to any of the following: Polymyxin B sulfate; Streptomycin sulfate; Chlortetracycline hydrochloride; Neomycin sulfate; No history of eczema or other exfoliative skin condition in patient or household contacts; HIV negative
• Other: No leukemia or lymphoma; No other malignancy within the past 3 years except superficial squamous cell or basal cell skin cancer or carcinoma in situ of the cervix or prostate; Not pregnant or nursing; Negative pregnancy test; Fertile patients must use effective contraception

Pennsylvania
      Kimmel Cancer Center of Thomas Jefferson University - Philadelphia, Philadelphia,  Pennsylvania,  19107-5541,  United States

Study chairs or principal investigators

Michael Joseph Mastrangelo,  Study Chair,  Kimmel Cancer Center (KCC)   

Study ID Numbers:  CDR0000064975; JMC-94-0843; NCI-H96-0965
Record last reviewed:  January 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00002817
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08