RATIONALE: Vaccines made from gp100 and sargramostim may make the body build an immune response to kill tumor cells.

PURPOSE: Phase I trial to study the effectiveness of vaccine therapy with gp100 and/or sargramostim in treating patients who have malignant melanoma.

Condition	Treatment or Intervention	Phase
Stage IV Melanoma stage III melanoma Recurrent Melanoma	Drug: gp100 antigen  Drug: sargramostim	Phase I

Further Study Details: 

OBJECTIVES: I. Determine the safety and toxicity of in vivo particle bombardment with DNA coated gold beads carrying cDNA for gp100, with or without gold beads carrying cDNA for sargramostim (GM-CSF), into uninvolved skin of patients with melanoma.

II. Estimate the intensity and duration of gp100 transgene expression following these regimens in these patients.

III. Assess local lymphocyte phenotype and systemic lymphocyte function following these regimens in these patients.

IV. Compare gp100 transgene expression as well as local lymphocyte phenotype and systemic lymphocyte function when the cDNA for GM-CSF is administered 3 days before cDNA for gp100 vs on the same day as gp100 administration in these patients.

V. Determine the effect of these regimens on tumor shrinkage, histological evidence of tumor inflammation or necrosis, or in vitro evidence of antitumor immune reactivity in these patients.

PROTOCOL OUTLINE: This is a dose escalation study. Patients are assigned to one of three treatment groups.

Group I: Patients receive particle mediated gene transfer (PMGT) of gp100 on day 1 to 2 or 4 separate sites. One site is biopsied on day 3. A second course is administered on day 22 and one of the sites is biopsied on day 26. Delayed type hypersensitivity (DTH) is assessed on days 40 and 43.

Group II: Patients receive PMGT of sargramostim (GM-CSF) on day 1 to 1-5 separate sites. PMGT of gp100 is administered to 2-4 of these same sites on day 4. One of the gp100 sites is biopsied on day 6. A second course is administered beginning on day 22, with one of the sites biopsied on day 29. DTH is assessed on days 40 and 43.

Group III: Patients receive PMGT of GM-CSF in combination with gp100 on day 1 to 2 or 4 separate sites. Courses are administered as in group I.

Patients who achieve partial or complete response or maintain stable disease may receive another course of therapy.

Cohorts of 3-6 patients are treated at each dose in each group 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.

Patients are followed at 3, 6, and 12 months, and then annually thereafter.

PROJECTED ACCRUAL: A total of 18 patients will be accrued for this study.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically proven malignant melanoma that is surgically or medically incurable
• Measurable or evaluable metastatic disease OR
• No evidence of disease following surgical resection of a distant metastasis OR Surgical resection of at least 2 local or regional recurrences, at least 1 of which had evidence of lymph node involvement; Each recurrence at least 1 month apart

--Prior/Concurrent Therapy--

• Biologic therapy: At least 1 month since prior immunotherapy
• Chemotherapy: At least 1 month since prior chemotherapy; No more than 2 prior chemotherapy regimens for melanoma
• Endocrine therapy: At least 1 month since prior steroids (except intermittent use as antiemetic or as topical agent); No concurrent steroids
• Radiotherapy: At least 1 month since prior radiotherapy; No prior radiotherapy to vaccine site
• Surgery: No prior organ allografts

--Patient Characteristics--

• Age: 18 and over
• Performance status: ECOG 0 or 1
• Life expectancy: Greater than 3 months
• Hematopoietic: WBC at least 3500/mm3; Platelet count at least 100,000/mm3; Hemoglobin at least 10.0 g/dL
• Hepatic: Bilirubin less than 2.0 mg/dL; SGOT less than 3 times normal
• Renal: Creatinine less than 2.0 mg/dL
• Other: Not pregnant; Fertile patients must use effective contraception; HIV negative; No active infections requiring antibiotic, antiviral, or antifungal therapy; No other active malignancy; No concurrent significant illnesses

Wisconsin
      University of Wisconsin Comprehensive Cancer Center, Madison,  Wisconsin,  53792,  United States

Study chairs or principal investigators

Mark R. Albertini,  Study Chair,  University of Wisconsin Comprehensive Cancer Center   

Study ID Numbers:  CDR0000067067; WCCC-CO-98601; NCI-T98-0045
Record last reviewed:  August 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003897
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08