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

NCT ID: NCT00601640

Last Updated: 2017-03-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 184 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-01-31
• Study Completion Date: 2014-12-31

Brief Summary

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.

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.

Conditions

Other Benign Neoplasm of Skin, Unspecified

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Eflornithine HCL

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

Group Type: EXPERIMENTAL

Eflornithine HCL ointment

Intervention Type: DRUG

Given topically twice daily on days 1-90

Diclofenac Na

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

Group Type: ACTIVE_COMPARATOR

Diclofenac Na gel

Intervention Type: DRUG

Given topically twice daily on days 1-90

Eflornithine HCL and Diclofenac Na

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

Group Type: EXPERIMENTAL

Diclofenac Na gel

Intervention Type: DRUG

Given topically twice daily on days 1-90

Eflornithine HCL ointment

Intervention Type: DRUG

Given topically twice daily on days 1-90

Interventions

Diclofenac Na gel

Given topically twice daily on days 1-90

Intervention Type: DRUG

Eflornithine HCL ointment

Given topically twice daily on days 1-90

Intervention Type: DRUG

Other Intervention Names

Solaraze; Vaniqa

Eligibility 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.

• Minimum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

University of Arizona

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Joanne M. Jeter, MD

Role: PRINCIPAL_INVESTIGATOR

University of Arizona

Locations

Virginia G. Piper Cancer Center at Scottsdale Healthcare - Shea

Tucson, Arizona, United States

Veterans Affairs Medical Center - Tucson

Tucson, Arizona, United States

Arizona Cancer Center at University of Arizona Health Sciences Center

Tucson, Arizona, United States

Countries

United States

References

Bozzo P, Saboda K, Einspahr JG, Ranger-Moore J, Farmer ER, Cockerell CJ, Elder DE, Bangert JL, Hart N, Kramer CB, Alberts DS. Reliability and validity of a histologic score as a marker for skin cancer chemoprevention studies. Anal Quant Cytol Histol. 2003 Oct;25(5):285-92.

Reference Type: BACKGROUND

PMID: 14603727 (View on PubMed)

Jeter JM, Curiel-Lewandrowski C, Stratton SP, Myrdal PB, Warneke JA, Einspahr JG, Bartels HG, Yozwiak M, Bermudez Y, Hu C, Bartels P, Alberts DS. Phase IIB Randomized Study of Topical Difluoromethylornithine and Topical Diclofenac on Sun-Damaged Skin of the Forearm. Cancer Prev Res (Phila). 2016 Feb;9(2):128-34. doi: 10.1158/1940-6207.CAPR-15-0232. Epub 2015 Dec 28.

Reference Type: DERIVED

PMID: 26712942 (View on PubMed)

Other Identifiers

P30CA023074

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P01CA027502

Identifier Type: NIH

Identifier Source: secondary_id

View Link

UARIZ-BIO-06182

Identifier Type: OTHER

Identifier Source: secondary_id

07-0032-04

Identifier Type: OTHER

Identifier Source: secondary_id

07-0032-04

Identifier Type: -

Identifier Source: org_study_id