Official Title: “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”

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.

Study Type: Interventional

Study Design: Prevention, Randomized

Study Primary Completion Date: June 2009

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. - 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 twice daily on days 1-90. - Arm III: Patients apply topical eflornithine hydrochloride ointment as in arm I and topical diclofenac sodium gel as in arm II twice 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.

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.

Intervention(s) in this Clinical Trial

• Drug: diclofenac sodium gel
  • Given topically twice daily on days 1-90
• Drug: eflornithine hydrochloride ointment
  • Given topically twice daily on days 1-90

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Arm I
  • Patients apply topical eflornithine hydrochloride ointment to their left forearm twice daily on days 1-90.
• Active Comparator: Arm II
  • Patients apply topical diclofenac sodium gel to their left forearm twice daily on days 1-90.
• Experimental: Arm III
  • Patients apply topical eflornithine hydrochloride ointment as in arm I and topical diclofenac sodium gel as in arm II twice daily on days 1-90.

Primary Measures

• 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

DISEASE CHARACTERISTICS:

• Visible sun-induced damage to the skin as assessed by the study dermatologists
• No inflammation of the skin on the lateral forearms
• No more than 10 actinic keratoses on the left forearm, and no actinic keratoses in the treatment area
• Resident of Pima or an adjoining Southern Arizona county
• Patients outside of Pima County are eligible but the study will be carried out in its entirety at the University of Arizona

PATIENT CHARACTERISTICS:

• History of treated basal cell carcinoma and/or squamous cell carcinoma of the skin at any site other than the left forearm allowed if excision or topical treatment was completed more than 30 days ago (60 days for radiotherapy)
• History of treated basal cell carcinoma and/or squamous cell carcinoma of the skin on the left forearm allowed 6 months after treatment is completed
• Must agree to avoid sun exposure to the left forearm as much as possible
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Not moderately to highly immunosuppressed by virtue of medication or disease, except for mildly suppressive disorders (e.g., diabetes mellitus or on mildly immunosuppressive therapy such as inhaled steroids for asthma)
• No serious concurrent illness that could interfere with study participation
• No active peptic ulcer disease, bleeding disorder, renal failure (creatinine > 2.0 mg/dL), or porphyria
• No known hypersensitivity to diclofenac sodium, eflornithine, acetylsalicylic acid, or

NSAIDS

• No evidence of serious underlying medical conditions as demonstrated by abnormal values on baseline laboratory assessment

PRIOR CONCURRENT THERAPY:

• More than 6 months since prior chemotherapy and in complete remission
• More than 60 days since prior and no concurrent oral diclofenac sodium (Cataflam®, Voltaren®, Voltaren-XR®) or combination of diclofenac and misoprostol (Arthrotec®)
• More than 60 days since prior and no concurrent IV eflornithine hydrochloride
• More than 30 days since prior and no concurrent topical retinoids, steroids, imiquimod (Aldara®), aminolevulinic acid HCl (Levulan®), eflornithine (Vaniqa®), diclofenac sodium gel (Solaraze®), or fluorouracil at any site
• More than 30 days since prior and no concurrent topical medication, other than emollients or sunscreens, on the left forearm
• Not undergoing concurrent bone marrow or solid organ transplant
• No other concurrent topical therapy at any site
• No concurrent immunosuppressive therapy (e.g., systemic chemotherapy or rheumatologic agents such as infliximab [Remicade®])
• No concurrent sunscreen use to the left forearm
• No concurrent active therapy for any invasive cancer
• No concurrent non-steroidal anti-inflammatory drugs (NSAIDs) for more than 14 days per month for arthritic and other pain conditions
• Concurrent daily aspirin (81-325 mg) or acetaminophen allowed
• Concurrent prednisone or other steroids with doses up to 20 mg/day (or the equivalent dose) allowed
• At least 30 days since prior and no concurrent enrollment on other investigational drug or device trial

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 40 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: University of Arizona

Overall Clinical Trial Officials and Contacts

Joanne M. Jeter, MD Principal Investigator University of Arizona  

Information obtained from ClinicalTrials.gov on September 05, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00601640

Study ID Number: CDR0000581429

ClinicalTrials.gov Identifier: NCT00601640

Health Authority: Unspecified

Clinical trial summary from the National Cancer Institute's PDQ® database