Acitretin in Preventing Skin Cancer in Patients at High Risk for Skin Cancer

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

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.

Study Overview

• Status: Completed
• Conditions: Non-melanomatous Skin Cancer
• Intervention / Treatment: Genetic: gene expression analysis; Genetic: protein expression analysis; Other: laboratory biomarker analysis; Genetic: polymerase chain reaction; Drug: acitretin; Genetic: northern blotting

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 130
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• At high risk for basal cell carcinoma (BCC) or squamous cell carcinoma (SCC) of the skin, defined as a prior history of ≥ 3 nonmelanoma skin lesions

  • All visible BCC or SCC must have been resected prior to study entry

PATIENT CHARACTERISTICS:

• Life expectancy > 5 years
• Alkaline phosphatase ≤ 2.5 times upper limit of normal (ULN)
• SGOT ≤ 2 times ULN
• Creatinine ≤ 1.5 times ULN
• Cholesterol < 250 mg/dL
• Triglycerides < 2.5 times ULN
• Not pregnant
• No history of significant, uncontrolled hyperlipidemia
• No history of oral retinoid intolerance
• No history of other significant medical condition that, in the opinion of the physician, would contraindicate retinoid use

PRIOR CONCURRENT THERAPY:

• More than 1 year since prior retinoid therapy

• At least 4 weeks since prior and no other concurrent use of oral vitamin A supplements, topical retinoids, or other potentially irritating skin preparations

  • Concurrent multivitamin supplements allowed
• No prior organ transplantation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Rate of new non-melanoma skin cancer development

Secondary Outcome Measures

Outcome Measure
Time to new non-melanoma skin cancer development
Gene expression (RAR/RXR, Fos/Jun, and AP-1)
HPV DNA detection, sequencing, and quantification

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Mark R. Pittelkow, MD, Mayo Clinic

Study record dates

Study Major Dates

• Study Start: February 1, 2003
• Primary Completion (Actual): May 1, 2006
• Study Completion (Actual): May 1, 2006

Study Registration Dates

• First Submitted: March 22, 2008
• First Submitted That Met QC Criteria: March 25, 2008
• First Posted (Estimate): March 26, 2008

Study Record Updates

• Last Update Posted (Estimate): May 16, 2011
• Last Update Submitted That Met QC Criteria: May 13, 2011
• Last Verified: May 1, 2011

More Information

Terms related to this study

• Keywords: squamous cell carcinoma of the skin; basal cell carcinoma of the skin
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Skin Neoplasms; Dermatologic Agents; Keratolytic Agents; Acitretin
• Other Study ID Numbers: CDR0000582327; P30CA015083 (U.S. NIH Grant/Contract); MC02C8 (Other Identifier: Mayo Clinic Cancer Center); 1153-98 (Other Identifier: Mayo Clinic IRB)