Phase 2a Randomized, Placebo-Controlled, Double-Blind Trial of Topical Perillyl Alcohol in Sun Damaged Skin
- 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.
- To determine if topically administered POH results in significant alterations in
surrogate endpoint biomarkers of epidermal cell proliferation, including optical
coherence tomography, p53 expression, c-Fos expression, and apoptosis (as measured by
activated caspase-3 expression).
- To determine if topically administered POH results in normalization of nuclear
chromatin patterns in skin biopsy tissue from these patients, as determined by
- To determine if topical POH can be administered safely to the forearms of these
OUTLINE: Patients are randomized to 1 of 3 arms.
- Arm I: Patients apply a placebo cream topically to each dorsal forearm twice daily for
3 months in the absence of unacceptable toxicity.
- Arm II: Patients apply perillyl alcohol (POH) cream (0.3%) topically to each dorsal
forearm twice daily for 3 months in the absence of unacceptable toxicity.
- Arm III: 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.
Allocation: Randomized, Masking: Double-Blind, Primary Purpose: Treatment
Change in histopathology grading
Steve Stratton, MD
University of Arizona
|Arizona Cancer Center at University of Arizona Health Sciences Center||Tucson, Arizona 85724|