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

Purpose

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.

Condition	Intervention	Phase
Non-melanomatous Skin Cancer	Drug: diclofenac sodium gel Drug: eflornithine hydrochloride ointment	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Prevention
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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Skin Cancer

Drug Information available for: Diclofenac sodium Diclofenac potassium Diclofenac Eflornithine hydrochloride

U.S. FDA Resources

Further study details as provided by University of Arizona:

Primary Outcome 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 [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Safety of combination therapy with topical eflornithine hydrochloride ointment and topical diclofenac sodium gel over 3-months [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
• Statistically significant reductions in karyometric measurements (nuclear abnormality) and biomarker expression (p53 and apoptosis) analyzed as percent immunohistochemical positive [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Enrollment:	184
Study Start Date:	January 2007
Study Completion Date:	January 2010
Primary Completion Date:	January 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Arm I Patients apply topical eflornithine hydrochloride ointment to their left forearm twice daily on days 1-90.	Drug: eflornithine hydrochloride ointment Given topically twice daily on days 1-90
Active Comparator: Arm II Patients apply topical diclofenac sodium gel to their left forearm once daily on days 1-90.	Drug: diclofenac sodium gel Given topically twice daily on days 1-90
Experimental: 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.	Drug: diclofenac sodium gel Given topically twice daily on days 1-90 Drug: eflornithine hydrochloride ointment Given topically twice daily on days 1-90

Detailed Description:

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 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.

Eligibility

Ages Eligible for Study:	40 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00601640

Locations

United States, Arizona
Arizona Cancer Center at University of Arizona Health Sciences Center
Tucson, Arizona, United States, 85724-5024
Veterans Affairs Medical Center - Tucson
Tucson, Arizona, United States, 85723
Virginia G. Piper Cancer Center at Scottsdale Healthcare - Shea
Tucson, Arizona, United States, 85258

Sponsors and Collaborators

University of Arizona

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Joanne M. Jeter, MD

University of Arizona

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	David Samuel Alberts, Arizona Cancer Center at University of Arizona Health Sciences Center
ClinicalTrials.gov Identifier:	NCT00601640 History of Changes
Other Study ID Numbers:	CDR0000581429, P30CA023074, P01CA027502, UARIZ-BIO-06182, 07-0032-04
Study First Received:	January 22, 2008
Last Updated:	September 28, 2010
Health Authority:	United States: Food and Drug Administration

Keywords provided by University of Arizona:

skin cancer

Additional relevant MeSH terms:

Skin Neoplasms
Neoplasms by Site
Neoplasms
Skin Diseases
Eflornithine
Diclofenac
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Trypanocidal Agents
Antiprotozoal Agents

Antiparasitic Agents
Anti-Infective Agents
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Cyclooxygenase Inhibitors
Central Nervous System Agents

ClinicalTrials.gov processed this record on June 18, 2013