Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Biomarker/Laboratory analysis, Prevention	Active	40 and over	NCI	UARIZ-BIO-06182 BIO #06-182, NCT00601640

Objectives

Primary

1. 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

1. To evaluate the safety of sequential administration of topical eflornithine hydrochloride ointment and topical diclofenac sodium gel.
2. To determine the correlation of karyometric changes with histopathologic, immunohistochemical, clinical, and genetic polymorphism data.
3. To obtain materials for microarray analysis.

Entry Criteria

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

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

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

Expected Enrollment

Outcomes

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

Safety of combination therapy with topical eflornithine hydrochloride ointment and topical diclofenac sodium gel over 3-months
• Statistically significant reductions in karyometric measurements (nuclear abnormality) and biomarker expression (p53 and apoptosis) analyzed as percent immunohistochemical positive

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 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.

Trial Contact Information

Trial Lead Organizations

Arizona Cancer Center at University of Arizona Health Sciences Center

Joanne Jeter, MD, Principal investigator		Ph: 520-626-9293; 800-622-2673 Email: jjeter@azcc.arizona.edu

U.S.A.
Arizona
	Tucson
	Arizona Cancer Center at University of Arizona Health Sciences Center
		Clinical Trials Office - Arizona Cancer Center at University of Arizona Health Sciences Center	Ph:  520-626-9008
	Veterans Affairs Medical Center - Tucson
		Joanne Jeter	Ph:  520-626-9293
	Virginia G. Piper Cancer Center at Scottsdale Healthcare - Shea
		Joanne Jeter	Ph:  520-626-9293

Registry Information
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
Trial Start Date		2007-01-16
Trial Completion Date		2009-06-30 (estimated)
Registered in ClinicalTrials.gov		NCT00601640
Date Submitted to PDQ		2008-01-07
Information Last Verified		2009-05-16
NCI Grant/Contract Number		CA027502, CA23074

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