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

Non-melanomatous Skin Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00644384
• Other study ID #: CDR0000582327
• Secondary ID: P30CA015083MC02C
• Status: Completed
• Phase: N/A
• First received: March 22, 2008
• Last updated: May 13, 2011
• Start date: February 2003
• Est. completion date: May 2006

Study information

• Verified date: May 2011
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 130
• Est. completion date: May 2006
• Est. primary completion date: May 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Masking: Double-Blind, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Carcinoma, Basal Cell
• Carcinoma, Squamous Cell
• Non-melanomatous Skin Cancer
• Skin Neoplasms

Intervention

Drug:
• acitretin

Genetic:
• gene expression analysis

• northern blotting

• polymerase chain reaction

• protein expression analysis

Other:
• laboratory biomarker analysis

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Mayo Clinic	National Cancer Institute (NCI)

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of new non-melanoma skin cancer development			No
Secondary	Time to new non-melanoma skin cancer development			No
Secondary	Gene expression (RAR/RXR, Fos/Jun, and AP-1)			No
Secondary	HPV DNA detection, sequencing, and quantification			No