Clinical trial NCT00644384: Acitretin in Preventing Skin Cancer in Patients at High Risk for Skin Cancer
Official title: Chemoprevention Trial of Acitretin Versus Placebo in Patients at High Risk for Basal Cell Carcinoma or Squamous Cell Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Non-melanomatous Skin Cancer
Keywords: basal cell carcinoma of the skin
squamous cell carcinoma of the skin
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2008-03-26
Enrollment: 130
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: PREVENTION

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Rate of new non-melanoma skin cancer development
Secondary outcomes:
measure: Time to new non-melanoma skin cancer development
measure: Gene expression (RAR/RXR, Fos/Jun, and AP-1)
measure: HPV DNA detection, sequencing, and quantification
Other outcomes:
Locations:
Study officials:
affiliation: Mayo Clinic
name: Mark R. Pittelkow, MD
role: PRINCIPAL_INVESTIGATOR
References: