Topical Perillyl Alcohol in Treating Patients With Sun Damaged Skin and Actinic Keratoses

Phase 2

Completed

Conditions: Precancerous Condition

Interventions: Other: placebo
Drug: perillyl alcohol

Registration Number: NCT00608634

Lead Sponsor: University of Arizona

Brief Summary: RATIONALE: Drugs used in chemotherapy, such as perillyl alcohol, work in different ways to stop the growth of abnormal cells, either by killing the cells or by stopping them from dividing. It is not yet known which dose of topical perillyl alcohol is more effective in stopping the development of cancer in sun damaged skin.

PURPOSE: This randomized phase II trial is studying high-dose topical perillyl alcohol to see how well it works compared with low-dose topical perillyl alcohol in treating patients with sun damaged skin and actinic keratoses.

Detailed Description: OBJECTIVES:

Primary

* To determine if topical administration of perillyl alcohol (POH) cream can reverse actinic damage as evidenced by normalization of quantitative skin histopathology scores in skin tissue biopsy samples from patients with moderate to severe sun damage.

Secondary

* To determine if topical POH can be administered safely to the forearms of these patients.

OUTLINE: Patients are randomized to 1 of 3 arms.

* Placebo: Patients apply a placebo cream topically to each dorsal forearm twice daily for 3 months in the absence of unacceptable toxicity.

* Low Dose: Patients apply perillyl alcohol (POH) cream (0.3%) topically to each dorsal forearm twice daily for 3 months in the absence of unacceptable toxicity.

* High Dose: Patients apply POH cream (0.76%) as in arm II. Patients undergo tissue sampling of the right or left dorsal forearm and of physician-selected representative actinic keratoses (AK) at baseline and after completion of study therapy. Tissue samples are assessed for changes in patterns of biomarker expression (i.e., p53, apoptosis, c-Fos histopathology) and karyometry. After completion of study therapy, patients undergo tissue sampling of the opposite forearm as well as blood sample collection to determine perillyl alcohol (POH) levels in blood and biopsy samples. Urine is also collected and analyzed for safety at the end of treatment. Digital photographs of the forearms and hands are obtained at baseline and after 3 months of study treatment. Optical coherence tomography imaging is also performed on pre- and post-biopsy sites to quantify the effect of POH on sun damage and AK in skin.

After completion of study treatment, patients are followed monthly.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 89

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	placebo	Patients apply a placebo cream topically to each dorsal forearm twice daily for 3 months in the absence of unacceptable toxicity.
High Dose POH 0.76%	perillyl alcohol	Patients apply perillyl alcohol (POH) cream (0.76%) topically to each dorsal forearm twice daily for 3 months in the absence of unacceptable toxicity.
Low Dose POH 0.30%	perillyl alcohol	Patients apply perillyl alcohol (POH) cream (0.3%) topically to each dorsal forearm twice daily for 3 months in the absence of unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Change in Histopathology Score of Sun Damaged Skin by Treatment Group	Baseline to 3 months	The histopathologic scoring for skin biopsies from sun-damaged skin to assess the following seven characteristics: 1- atypia (levels 0, 1 \& 2), 2- inflammation (grades 0, 1 \& 2), 3- hyperkeratosis (loss of basket weave pattern of stratum corneum), 4- parakeratosis (present when there were \>3 characteristic nuclei per 40:1 field in stratum corneum), 5- dyskeratosis (focal presence of cells with homogenous, pink cytoplasm n pyknotic nuclei), 6- epidermotropism (lymphocytes migration of \>3 cells into epidermis, 7- loss of granular layer. All assessments were done using a 40:1 objective.

Secondary Outcome Measures

Name	Time	Method
Skin Related Events From Perillyl Alcohol at Administered Doses by Participants	3 months	The events do not have to be caused by the drug or therapy, and they may be mild, moderate, or severe. (NCI)