Skin Cancer Prevention - Full Text View

Sponsor:	Department of Veterans Affairs
Information provided by (Responsible Party):	Department of Veterans Affairs
ClinicalTrials.gov Identifier:	NCT00847912

Purpose

The main purpose of this study is to see if 5-fluorouracil (5-FU) skin cream can prevent the growth of new skin cancers on the face and ears. The cost of trying to prevent skin cancer will be compared to the usual cost of treating skin cancer. You are being asked to be a part of this study because you have been treated for two or more skin cancers within the past five (5) years. At least one of these cancers occurred on your face or ears. Having had two or more skins cancers in the past 5 years makes it likely that you will develop additional skin cancers in the future.

Exposure to ultraviolet radiation from the sun or artificial sources such as tanning beds is a major cause of basal cell and squamous cell carcinoma of the skin. Using lotions, creams, or gels that contain sunscreens can help protect the skin from premature aging and damage that may lead to skin cancer.

The 5-FU skin cream used in this study is FDA-approved to treat some types of skin cancers and spots that might become skin cancer. However, 5-FU skin cream has never been studied to see if it can prevent skin cancer. This drug is not approved by the FDA for how it will be used in this study.

In this study, one half of the patients will use the 5-FU cream and the other half will use a skin cream that looks identical to the 5-FU cram but does not have 5-FU or any other active drug in it.

Approximately twelve VA medical centers will work together in this study. About one thousand (1000) patients will be in this study. The study is sponsored by the U.S. Department of Veterans Affairs Cooperative Studies Program.

Condition	Intervention	Phase
Carcinoma, Basal Cell Carcinoma, Squamous Cell Skin Neoplasms Skin Diseases Neoplasms, Basal Cell Neoplasms, Squamous Cell Carcinoma	Drug: 5-fluorouracil Drug: Placebo, vehicle control	Phase IV

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Prevention
Official Title:	CSP #562 - The VA Keratinocyte Carcinoma Chemoprevention Trial

Resource links provided by NLM:

MedlinePlus related topics: Cancer Skin Cancer Skin Conditions

Drug Information available for: Fluorouracil

U.S. FDA Resources

Further study details as provided by Department of Veterans Affairs:

Primary Outcome Measures:

The time to diagnosis of the first Keratinocyte Carcinoma on the face or ears for which surgery is performed [ Time Frame: Either scheduled follow-up visits (every 6 months) or at examination requested by patient ] [ Designated as safety issue: No ]

Estimated Enrollment:	1000
Study Start Date:	June 2009
Estimated Study Completion Date:	March 2014
Estimated Primary Completion Date:	June 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 Group assigned to blinded 5-FU cream applied to face and ears twice daily for maximum of 56 doses	Drug: 5-fluorouracil Apply thin layer of topical 5-FU 5% cream twice daily to face and ears for 4 weeks. Treatment to be initiated immediately after randomization. If unable to tolerate the twice daily 5-FU, they will discontinue the treatment and initiate "cool-down" treatment with triamcinolone 0.1% cream twice daily until the symptoms resolve. At 3 weeks after stopping 5-FU, if and only if the participant has not received at least the minimum 2 week (28 dose) course, 5-FU treatment will be resumed on a once-daily basis to complete the 56 dose course. If this is not tolerated, the "cool-down" routine will be followed, but 5-FU will be stopped. Other Name: Efudex, 5-FU
Placebo Comparator: 2 Group assigned to blinded vehicle control cream applied to face and ears twice daily for maximum of 56 doses	Drug: Placebo, vehicle control Apply thin layer of vehicle control cream twice daily to face and ears for 4 weeks. Treatment to be initiated immediately after randomization. If unable to tolerate the twice daily vehicle control cream, they will discontinue the treatment and initiate "cool-down" treatment with triamcinolone 0.1% cream twice daily until the symptoms resolve. At 3 weeks after stopping vehicle control cream, if and only if the participant has not received at least the minimum 2 week (28 dose) course, vehicle control cream treatment will be resumed on a once-daily basis to complete the 56 dose course. If this is not tolerated, the "cool-down" routine will be followed, but vehicle control cream will be stopped. Other Name: Placebo

Arms

Assigned Interventions

Experimental: 1

Group assigned to blinded 5-FU cream applied to face and ears twice daily for maximum of 56 doses

Drug: 5-fluorouracil

Apply thin layer of topical 5-FU 5% cream twice daily to face and ears for 4 weeks. Treatment to be initiated immediately after randomization. If unable to tolerate the twice daily 5-FU, they will discontinue the treatment and initiate "cool-down" treatment with triamcinolone 0.1% cream twice daily until the symptoms resolve. At 3 weeks after stopping 5-FU, if and only if the participant has not received at least the minimum 2 week (28 dose) course, 5-FU treatment will be resumed on a once-daily basis to complete the 56 dose course. If this is not tolerated, the "cool-down" routine will be followed, but 5-FU will be stopped.

Other Name: Efudex, 5-FU

Placebo Comparator: 2

Group assigned to blinded vehicle control cream applied to face and ears twice daily for maximum of 56 doses

Drug: Placebo, vehicle control

Apply thin layer of vehicle control cream twice daily to face and ears for 4 weeks. Treatment to be initiated immediately after randomization. If unable to tolerate the twice daily vehicle control cream, they will discontinue the treatment and initiate "cool-down" treatment with triamcinolone 0.1% cream twice daily until the symptoms resolve. At 3 weeks after stopping vehicle control cream, if and only if the participant has not received at least the minimum 2 week (28 dose) course, vehicle control cream treatment will be resumed on a once-daily basis to complete the 56 dose course. If this is not tolerated, the "cool-down" routine will be followed, but vehicle control cream will be stopped.

Other Name: Placebo

Detailed Description:

Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) of the skin, both of which are keratinocyte carcinomas (KCs), account for a half of all cancers in the United States, and over 100,000 diagnoses per year in the VA. The standard treatment for these KCs is excision of the lesion, and they cost the US health care system some $2.5 billion annually and about $100 million annually in the VA. There is no proven means to prevent KCs (except perhaps for a modest benefit of intensive daily sunscreen use). An effective prevention strategy would dramatically change the way high-risk patients are managed and could substantially reduce the costs of care. Our preliminary analysis indicates that the savings will be $116 per high-risk patient and will account for a total national savings of over $11 million. These findings imply that the study would pay for itself by the end of 4 years. We hypothesize that topical 5-fluourouracil (5-FU) chemoprevention will prevent skin cancer surgeries and will be cost-saving. To test this we propose a randomized controlled trial of 5-FU compared to a vehicle control to the face and ears in a high-risk population.

In the study, 1000 veterans at high-risk of skin cancer defined as at least 2 KCs in the prior 5 years, at least one of which was on the face or ears, will be randomized to 5-FU or a vehicle control cream, and followed for 2 to 4 years. The primary endpoint will be surgery for any KC on the face and ears. We will also assess the cost of care, quality of life, the side effects associated with treatment, and the prevalence and number of actinic keratoses, a skin cancer precursor and itself a cause of morbidity and cost. By targeting patients at high-risk, the study focuses on high-cost patients for whom this treatment could both improve outcomes (cancers and quality of life) and reduce costs.

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Veteran who is at high risk for developing skin cancer defined as 2 keratinocyte carcinomas in the past 5 years, at least one of which was located on the face or ears

Exclusion Criteria:

Participants who are unable to speak English
Participants with KC at randomization
Participants currently using or having used field therapy for AKs on the face or ears in the past 3 years. The vast majority of these field treatments would have been with 5-FU cream. We will allow recent use of therapies that are applied to individual AK lesions (e.g. cryotherapy), but not those that were used on an entire area (field) in the study treatment area Participants currently using or having used systemic 5-fluorouracil or oral capecitabine (Xeloda) within the past 3 years Participants with known allergy to sunscreen, triamcinolone and/or 5-fluorouracil.

Exclusions 6-l0: We will exclude the small proportion who get their KCs for special reasons other than ultraviolet radiation exposure (see list below), since that etiologic difference, which is associated with a prognostic difference, could be associated with a biologic difference in response to chemoprevention efforts. These will include:

Solid organ transplant recipients, such as renal, hepatic, or cardiac transplant patients
Individuals with genetic disorders associated with very high cancer risk such as:
basal cell nevus syndrome
erythrodysplasia verruciformis
xeroderma pigmentosum
Arsenic exposure
PUVA (Psoralen plus UVA) treatment
Cutaneous T-cell lymphoma
Prior or current radiation therapy to the face and/or ears.

Additional exclusions (12-15) are:

Those who, in the opinion of the recruiting investigator, have very high mortality risk at randomization (less than 50% chance of surviving 4 years) due to co morbid illness such as metastatic cancer or COPD.
For women of childbearing potential an initial pregnancy test and ongoing birth control will be required for participation.
Patients with known dihydropyrimidine dehydrogenase (DPD) enzyme deficiency by self report or noted in the medical record (they have increased toxicity from systemic 5-FU, although screening for this is not part of dermatologic practice and will not be part of this study).
Patients on methotrexate (these will constitute about 1% of potentially eligible individuals) because they may have more severe reactions to topical 5-FU.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00847912

Locations

United States, California
VA Palo Alto Health Care System
Palo Alto, California, United States, 94304-1290
VA San Diego Healthcare System, San Diego
San Diego, California, United States, 92161
United States, Colorado
VA Eastern Colorado Health Care System, Denver
Denver, Colorado, United States, 80220
United States, Florida
VA Medical Center, Bay Pines
Bay Pines, Florida, United States, 33708
VA Medical Center, Miami
Miami, Florida, United States, 33125
United States, Georgia
Atlanta VA Medical and Rehab Center, Decatur
Decatur, Georgia, United States, 30033
United States, Illinois
Edward Hines, Jr. VA Hospital
Hines, Illinois, United States, 60141-5000
United States, Massachusetts
VA Medical Center, Jamaica Plain Campus
Boston, Massachusetts, United States, 02130
United States, Minnesota
VA Medical Center, Minneapolis
Minneapolis, Minnesota, United States, 55417
United States, North Carolina
VA Medical Center, Durham
Durham, North Carolina, United States, 27705
United States, Pennsylvania
VA Medical Center, Philadelphia
Philadelphia, Pennsylvania, United States, 19104
United States, Rhode Island
VA Medical Center, Providence
Providence, Rhode Island, United States, 02908
United States, Tennessee
VA Medical Center
Nashville, Tennessee, United States, 37212-2637

Sponsors and Collaborators

Department of Veterans Affairs

Investigators

Study Chair:

Martin A. Weinstock, MD

VA Medical Center, Providence

More Information

No publications provided

Responsible Party:	Department of Veterans Affairs
ClinicalTrials.gov Identifier:	NCT00847912 History of Changes
Other Study ID Numbers:	562
Study First Received:	February 18, 2009
Last Updated:	January 9, 2012
Health Authority:	United States: Federal Government; United States: Food and Drug Administration

Keywords provided by Department of Veterans Affairs:

NMSC
nonmelanoma skin cancer
topical 5-FU 5% cream
Neoplasms
Antineoplastic Agents

Therapeutic Uses
Dermatologic Agents
Neoplasms by Site
carcinoma, basal cell
carcinoma, squamous cell

Additional relevant MeSH terms:

Neoplasms
Carcinoma
Skin Neoplasms
Carcinoma, Basal Cell
Carcinoma, Squamous Cell
Skin Diseases
Neoplasms, Basal Cell
Neoplasms, Squamous Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms by Site

Antineoplastic Agents
Fluorouracil
Dermatologic Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on February 09, 2012