This randomized phase II trial is studying how well sulindac works in preventing melanoma in healthy participants who are at increased risk of melanoma. Sulindac may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether sulindac is more effective than a placebo in preventing melanoma in individuals with many moles and abnormal moles.
PRIMARY OBJECTIVE: I. To determine sulindac and metabolite levels in healthy participants with atypical nevi and benign nevus at increased risk for melanoma treated with sulindac versus placebo. SECONDARY OBJECTIVES: I. To assess the effects of sulindac on apoptosis in atypical nevi of these participants. II. To assess the effects of sulindac on VEGF expression in atypical nevi of these participants. III. To assess sulindac and metabolite levels in plasma and its association with drug levels in the target tissue. OUTLINE: This is a multicenter study. Participants are randomized to 1 of 2 treatment arms. ARM I: Participants receive oral sulindac twice daily. ARM II: Participants receive oral placebo twice daily. In both arms, treatment continues for 8 weeks in the absence of unacceptable toxicity. Blood and tissue samples are collected at baseline and/or after completion of study therapy and analyzed for sulindac and metabolite levels via high performance liquid chromatography tandem mass spectrometry; the detection of apoptotic cells via TUNEL assay; and VEGF expression via immunohistochemistry assays. After completion of study therapy, participants are followed for 2 weeks.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
DOUBLE
Enrollment
50
University of Arizona Health Sciences Center
Tucson, Arizona, United States
Stanford University Hospitals and Clinics
Stanford, California, United States
Sulindac Concentration in the Nevi (Moles)
Time frame: 8 weeks
Sulindac Sulfone, an Active Metabolite of Sulindac, Concentration in the Nevi
Time frame: 8 weeks
Sulindac Sulfide, an Active Metabolite of Sulindac, Concentration in the Nevi
Time frame: 8 weeks
Sulindac Effects on Apoptosis in Atypical Nevi
Change in the expression of a marker of apoptosis, cleaved caspase 3, in melanocytic junctional component
Time frame: Baseline and 8 weeks
Sulindac Effects on Vascular Endothelial Growth Factor (VEGF) Expression in Atypical Nevi
Change in VEGF expression in melanocytic junctional component
Time frame: Baseline and 8 weeks
Association Between Plasma and Target Tissue Sulindac Levels
Time frame: 8 weeks
Association Between Plasma and Target Tissue Sulindac Sulfone Levels
Time frame: 8 weeks
Association Between Plasma and Target Tissue Sulindac Sulfide Levels
Time frame: 8 weeks
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