Neoplasms

Skin and Connective Tissue Diseases

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Skin Neoplasms

Skin Diseases

Anti-Inflammatory Agents

Antirheumatic Agents

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All Drugs and Chemicals

Anti-Infective Agents

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Amino Acids

Diclofenac

Eflornithine

Anti-Inflammatory Agents, Non-Steroidal

Analgesics, Non-Narcotic

Cyclooxygenase Inhibitors

Enzyme Inhibitors

Antiprotozoal Agents

Antiparasitic Agents

Ornithine

Patients apply Eflornithine HCL ointment to their left forearm twice daily on days 1-90.

Patients apply topical Diclofenac Na gel to their left forearm once daily on days 1-90.

Eflornithine HCl ointment and Diclofenac Na gel applied twice and once daily, respectively on days 1-90.

Diclofenac Na gel

Eflornithine HCL ointment

Joanne M. Jeter, MD

RATIONALE: Chemoprevention is the use of certain drugs to keep cancer from forming. The use of eflornithine and diclofenac may stop cancer from growing in patients with sun-damaged skin.

PURPOSE: This randomized phase II trial is studying the side effects and how well eflornithine works compared with diclofenac, given alone or together, in treating patients with sun-damaged skin.

OBJECTIVES:

Primary

* 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.

Secondary

* 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.

* Eflornithine hydrochloride : Patients apply topical eflornithine hydrochloride ointment to their left forearm twice daily on days 1-90.
* Diclofenac sodium : Patients apply topical diclofenac sodium gel to their left forearm once daily on days 1-90.
* Eflornithine hydrochloride/Diclofenac sodium : 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 treatment.

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.

Eflornithine and/or Diclofenac in Treating Patients With Sun-Damaged Skin

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

Putrescine is measured in nmole/g skin per biopsy. Baseline and End of Study biopsies were measured and the change was produced by subtracting baseline levels from End of Study levels. There was one baseline biopsy and one End of Study biopsy per participant.

Adverse events were compared across three treatment groups by severity determined by the clinician. All adverse events were resolved by the end of follow up.

Change scores were computed by subtracting baseline histologic score from End of Study histologic score. Slides were formalin fixed. Histologic Score has been developed by this research group over the course of Grant (reference below). A standardized form captures data on the following criteria: basal or suprabasilar pleomorphism (atypia); inflammation; hyperkeratosis; parakeratosis. The atypia and inflammation were rated as: none (0), mild to moderate(1), and severe (2). The remaining criteria were rated as present (1) or absent (0). Histologic Scores were computed by adding together the codes for the histologic criteria. Higher scores reflected higher level of epidermal /dermal damage.

National Cancer Institute (NCI)

University of Arizona

Patients apply topical eflornithine hydrochloride ointment to their left forearm twice daily on days 1-90.

Arm I

Patients apply topical diclofenac sodium gel to their left forearm once daily on days 1-90.

Arm II

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.

Arm III

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

Joanne Jeter, MD

Eflornithine Hydrochloride

Diclofenac Sodium

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.

Eflornithine Hydrochloride/Diclofenac Sodium

Changes in Putrescine Over 3 Months

Burning and Stinging None

Burning and stinging Mild

burning and stinging Moderate

Burning and Stinging Severe

Pruritis None

Pruritis Mild

Pruritis Moderate

Pruritis Severe

Rash, Redness. Erythema-None

Rash, Redness. Erythema-Mild

Rash, Redness. Erythema-Moderate

Rash, Redness. Erythema-Severe

Patients apply topical eflornithine hydrochloride ointment to their left forearm twice daily on days 1-90

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

Safety of Combination Therapy With Topical Eflornithine Hydrochloride Ointment and Topical Diclofenac Sodium Gel Over 3-months

Change in Histologic Score Diagnosis and Treatment Group

Overall Study

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Eflornithine and/or Diclofenac in Treating Patients With Sun-Damaged Skin	NCT00601640	Other Benign Ne...	Diclofenac Na g... Eflornithine HC...	40 Years -	University of Arizona
Eflornithine and/or Diclofenac in Treating Patients With Sun-Damaged Skin	NCT00601640	Other Benign Ne...	Diclofenac Na g... Eflornithine HC...	40 Years -	University of Arizona
Eflornithine and/or Diclofenac in Treating Patients With Sun-Damaged Skin	NCT00601640	Other Benign Ne...	Diclofenac Na g... Eflornithine HC...	40 Years -	University of Arizona

Spots Global Cancer Trial Database for diclofenac na gel