Acitretin in Preventing Skin Cancer in Patients at High Risk for Skin Cancer
RATIONALE: Chemoprevention is the use of certain drugs to keep cancer from forming. The use of acitretin may stop cancer from growing in patients at high risk for basal cell carcinoma or squamous cell carcinoma of the skin.
PURPOSE: This randomized trial is studying how well acitretin works in preventing skin cancer in patients at high risk for skin cancer.
Non-melanomatous Skin Cancer
Genetic: gene expression analysis
Genetic: northern blotting
Genetic: polymerase chain reaction
Genetic: protein expression analysis
Other: laboratory biomarker analysis
|Study Design:||Allocation: Randomized
Primary Purpose: Prevention
|Official Title:||Chemoprevention Trial of Acitretin Versus Placebo in Patients at High Risk for Basal Cell Carcinoma or Squamous Cell Carcinoma|
- Rate of new non-melanoma skin cancer development [ Designated as safety issue: No ]
- Time to new non-melanoma skin cancer development [ Designated as safety issue: No ]
- Gene expression (RAR/RXR, Fos/Jun, and AP-1) [ Designated as safety issue: No ]
- HPV DNA detection, sequencing, and quantification [ Designated as safety issue: No ]
|Study Start Date:||February 2003|
|Study Completion Date:||May 2006|
|Primary Completion Date:||May 2006 (Final data collection date for primary outcome measure)|
- Determine the chemopreventive efficacy of acitretin, a synthetic retinoid, in patients at high risk for basal cell carcinoma (BCC) or squamous cell carcinoma (SCC) of the skin.
- Evaluate human papillomavirus (HPV) as a possible etiologic cofactor in the development of cutaneous epidermal dysplasia/carcinoma from skin tissues of patients at high risk for BCC or SCC of the skin.
- Determine the effect of acitretin on a series of potential surrogate endpoint biomarkers (SEBs), including specific retinoid receptors; the Fos/Jun family of proto-oncogenes and products; the Fos/Jun family of transcription factor complexes known as activating protein 1 (AP-1); and HPV DNA in normal (sun-protected), sun-exposed dysplastic and carcinoma (SCC/BCC) skin specimens.
- Correlate standard clinical and histopathological dermatologic evaluation with modulation of SEBs.
OUTLINE: This is a multicenter study. Patients are stratified according to age (18-49 years vs 50-59 years vs 60-69 years vs ≥ 70 years), number of skin cancers within the past 5 years (2-5 vs 6-10 vs 11-20 vs 21-30 vs > 30), most recent skin cancer occurrence (< 12 months ago vs ≥ 12 months ago), patient-reported sunburn susceptibility by Fitzpatrick skin type (1 vs 2 vs 3 vs 4 vs 5 vs 6), and assessment of visible skin damage (minimal vs moderate vs extensive). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive oral acitretin 5 days a week for 2 years in the absence of unacceptable toxicity.
- Arm II: Patients receive oral placebo 5 days a week for 2 years in the absence of unacceptable toxicity.
Tissue samples of normal skin, excised squamous cell or basal cell carcinoma, or excised actinic keratoses are obtained at baseline and periodically during study. Tissue samples are analyzed for surrogate endpoint biomarkers, including RARγ, RXRα, Fos/Jun family of proto-oncogenes and products, AP-1 DNA binding activity, and presence, identification, and quantification of HPV DNA. mRNA and protein expression levels of RARγ, RXRα, and Fos/Jun family members are analyzed by northern blotting and/or quantitative polymerase chain reaction (PCR) methods. HPV is analyzed by PCR.
After completion of study treatment, patients are followed every 6 months for up to 5 years.
|Principal Investigator:||Mark R. Pittelkow, MD||Mayo Clinic|