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

This study has been completed.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University of Arizona
ClinicalTrials.gov Identifier:
NCT00601640
First received: January 22, 2008
Last updated: February 2, 2017
Last verified: February 2017
  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
Other Benign Neoplasm of Skin, Unspecified Drug: Diclofenac Na gel Drug: Eflornithine HCL ointment Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
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:


Further study details as provided by University of Arizona:

Primary Outcome Measures:
  • Changes in Putrescine Over 3 Months [ Time Frame: 3 months ]
    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.

  • Safety of Combination Therapy With Topical Eflornithine Hydrochloride Ointment and Topical Diclofenac Sodium Gel Over 3-months [ Time Frame: 3 months ]
    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.


Secondary Outcome Measures:
  • Change in Histologic Score Diagnosis and Treatment Group [ Time Frame: 3 months ]
    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.


Enrollment: 184
Study Start Date: January 2007
Study Completion Date: December 2014
Primary Completion Date: February 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Eflornithine HCL
Patients apply Eflornithine HCL ointment to their left forearm twice daily on days 1-90.
Drug: Eflornithine HCL ointment
Given topically twice daily on days 1-90
Other Name: Vaniqa
Active Comparator: Diclofenac Na
Patients apply topical Diclofenac Na gel to their left forearm once daily on days 1-90.
Drug: Diclofenac Na gel
Given topically twice daily on days 1-90
Other Name: Solaraze
Experimental: Eflornithine HCL and Diclofenac Na
Eflornithine HCl ointment and Diclofenac Na gel applied twice and once daily, respectively on days 1-90.
Drug: Diclofenac Na gel
Given topically twice daily on days 1-90
Other Name: Solaraze
Drug: Eflornithine HCL ointment
Given topically twice daily on days 1-90
Other Name: Vaniqa

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.

  • 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.

  Eligibility

Ages Eligible for Study:   40 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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
  • 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
  • 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
  • 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 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 NSAIDs for more than 14 days per month for arthritic and other pain conditions
  • 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

Exclusion Criteria:

  • Individuals receiving concurrent topical therapy with retinoids, steroids, 5-fluorouracil, Levulan, Vaniqa (eflornithine), Solaraze, or Imiquimod (Aldara®) within 30 days prior to study enrollment will be excluded. Subjects may be reconsidered for eligibility 30 days after the last topical treatment.
  • Individuals who have had treatment for basal cell carcinoma or squamous cell carcinoma of the skin of the left forearm within six months prior to evaluation for the study will not be eligible. If interested, these subjects will be encouraged to return for re-evaluation once the six-month period is over.
  • Individuals who are moderately to highly immunosuppressed by virtue of medication or disease will not be allowed to participate. This category includes individuals undergoing bone marrow or solid organ transplant, or receiving immunosuppressive therapy such as systemic chemotherapy or rheumatologic agents such as infliximab (Remicade®). However, individuals with mildly suppressive disorders such as diabetes mellitus or on mildly immunosuppressive therapy such as inhaled steroids for asthma will be eligible for participation. Doses up to 20 mg of prednisone per day or the equivalent dose of other steroids will be allowed.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
United States, Arizona
Virginia G. Piper Cancer Center at Scottsdale Healthcare - Shea
Tucson, Arizona, United States, 85258
Veterans Affairs Medical Center - Tucson
Tucson, Arizona, United States, 85723
Arizona Cancer Center at University of Arizona Health Sciences Center
Tucson, Arizona, United States, 85724-5024
Sponsors and Collaborators
University of Arizona
National Cancer Institute (NCI)
Investigators
Principal Investigator: Joanne M. Jeter, MD University of Arizona
  More Information

Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University of Arizona
ClinicalTrials.gov Identifier: NCT00601640     History of Changes
Other Study ID Numbers: 07-0032-04
P30CA023074 ( US NIH Grant/Contract Award Number )
P01CA027502 ( US NIH Grant/Contract Award Number )
UARIZ-BIO-06182 ( Other Identifier: UA IRB no. )
07-0032-04 ( Other Identifier: UA IRB )
Study First Received: January 22, 2008
Results First Received: April 15, 2011
Last Updated: February 2, 2017

Keywords provided by University of Arizona:
skin cancer

Additional relevant MeSH terms:
Skin Neoplasms
Neoplasms
Neoplasms by Site
Skin Diseases
Eflornithine
Diclofenac
Antineoplastic Agents
Trypanocidal Agents
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Ornithine Decarboxylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
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

ClinicalTrials.gov processed this record on June 28, 2017