Phase IIB Study to Evaluate the Safety and Efficacy of Topical Difluoromethylornithine and Topical Diclofenac in the Treatment of Sun-Damaged Skin on the Forearm
- To determine if combination therapy with topical eflornithine hydrochloride ointment
and topical diclofenac sodium gel over 3-months increases the efficacy versus either
agent used alone in the treatment of moderately sun-damaged skin.
- To evaluate the safety of sequential administration of topical eflornithine
hydrochloride ointment and topical diclofenac sodium gel.
- To determine the correlation of karyometric changes with histopathologic,
immunohistochemical, clinical, and genetic polymorphism data.
- To obtain materials for microarray analysis.
OUTLINE: Patients are randomized to 1 of 3 treatment arms.
- Arm I: Patients apply topical eflornithine hydrochloride ointment to their left forearm
twice daily on days 1-90.
- Arm II: Patients apply topical diclofenac sodium gel to their left forearm once daily
on days 1-90.
- Arm III: Patients apply topical eflornithine hydrochloride ointment as in arm I twice
daily and topical diclofenac sodium gel as in arm II once daily on days 1-90.
Prior to treatment, three 4-mm punch biopsies are taken from the skin of the left lateral
forearm for assessment of histopathology, the cyclooxygenase-2 enzyme and p53 expression,
apoptosis, and nuclear chromatin karyometry. Tissue is also obtained for future use in
microarray analysis. Blood is drawn for assessment of ornithine decarboxylase polymorphisms
and for banking for subsequent studies. Biopsies are repeated 2-3 weeks after completion of
Digital photographs are taken at baseline and 1-2 weeks after completion of study therapy to
document improvement of sun damage, appearance of new skin lesions, and toxicity.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention
Percentage of patients who have 10% or greater reduction in average nuclear abnormality (ANA) as shown by karyometric analysis of skin biopsies before and after treatment
Joanne M. Jeter, MD
University of Arizona
United States: Food and Drug Administration
|Veterans Affairs Medical Center - Tucson||Tucson, Arizona 85723|
|Arizona Cancer Center at University of Arizona Health Sciences Center||Tucson, Arizona 85724|
|Virginia G. Piper Cancer Center at Scottsdale Healthcare - Shea||Scottsdale, Arizona 85260|