Trial Information

Chemoprevention Trial of Acitretin Versus Placebo in Patients at High Risk for Basal Cell Carcinoma or Squamous Cell Carcinoma

OBJECTIVES:

- 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.