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Carcinoma, Basal CellPhase 4VAKCCTNCT00847912

CSP #562 - The VA Keratinocyte Carcinoma Chemoprevention Trial

A Phase 4 study testing 5-fluorouracil in people with Carcinoma, Basal Cell and Carcinoma, Squamous Cell, run by VA Office of Research and Development at 13 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Any age
What is being tested?
5-fluorouracil
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
954 participants
Where
13 sitesUnited States
Study dates
26 Jun 2009to 30 Jul 2016
Phase
Phase 4
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Any age
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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. The investigators 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: The investigators 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:
Show all 18Show fewer
  • 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.

Trial locations and contacts

13 sites in 1 country.

13 sites in 1 country

United States13 sites

  • Bay Pines VA Healthcare System, Pay Pines, FL

    Bay Pines, Florida, 33744

  • VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA

    Boston, Massachusetts, 02130

  • Atlanta VA Medical and Rehab Center, Decatur, GA

    Decatur, Georgia, 30033

  • VA Eastern Colorado Health Care System, Denver, CO

    Denver, Colorado, 80220

  • Durham VA Medical Center, Durham, NC

    Durham, North Carolina, 27705

  • Edward Hines Jr. VA Hospital, Hines, IL

    Hines, Illinois, 60141-5000

  • Miami VA Healthcare System, Miami, FL

    Miami, Florida, 33125

  • Minneapolis VA Health Care System, Minneapolis, MN

    Minneapolis, Minnesota, 55417

  • Tennessee Valley Healthcare System Nashville Campus, Nashville, TN

    Nashville, Tennessee, 37212-2637

  • VA Palo Alto Health Care System, Palo Alto, CA

    Palo Alto, California, 94304-1290

  • Philadelphia VA Medical Center, Philadelphia, PA

    Philadelphia, Pennsylvania, 19104

  • Providence VA Medical Center, Providence, RI

    Providence, Rhode Island, 02908

  • VA San Diego Healthcare System, San Diego, CA

    San Diego, California, 92161

Other trials in United States

About this study

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. Participants are being asked to be a part of this study because the participants have been treated for two or more skin cancers within the past five (5) years. At least one of these cancers occurred on the face or ears. Having had two or more skins cancers in the past 5 years makes it likely that participants 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.

Read more

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 cream 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.

Read the 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. The investigators' 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. The investigators hypothesize that topical 5-fluorouracil (5-FU) chemoprevention will prevent skin cancer surgeries and will be cost-saving. To test this the investigators 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. The investigators 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.

Being tested
5-fluorouracil, Placebo, vehicle control
Keywords
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
Medical subject headings
Carcinoma, Basal Cell, Carcinoma, Squamous Cell, Skin Neoplasms, Skin Diseases, Neoplasms, Basal Cell, Neoplasms, Squamous Cell, Carcinoma, Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 5-fluorouracilDrug

    Also called Efudex, 5-FU

    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.

  • Placebo, vehicle controlDrug

    Also called Placebo

    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.

Study groups in NCT00847912
Study groupRoleWhat they receive
Arm 1: 5-fluorouracilExperimentalGroup assigned to blinded 5-FU (5-fluorouracil) cream applied to face and ears twice daily for maximum of 56 doses
Receives: Drug: 5-fluorouracil
Arm 2: PlaceboPlacebo comparatorGroup assigned to blinded placebo, vehicle control cream applied to face and ears twice daily for maximum of 56 doses
Receives: Drug: Placebo, vehicle control

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The Time to Diagnosis of the First Keratinocyte Carcinoma (KC) on the Face or Ears for Which Surgery is Performed

    Diagnosis of the first Primary Basil Cell Carcinoma (BCC) or primary Squamous Cell Carcinoma (SCC) on the face or ears that was removed surgically.

    Measured: From randomization to last visit prior to end of study date (6/30/2013), assessed up to four years

  2. Hazard Ratio for Surgically Treated KC

    Measured: date of randomization to last visit before end of study follow up (6/30/2013), assessed up to four years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Feb 2009 (estimated)
  2. Study start26 Jun 2009
  3. Primary completion28 Jun 2013
  4. Study completion30 Jul 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
954 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00847912
Sponsor's protocol ID
562
Acronym
VAKCCT
Status last verified
May 2021
First submitted
18 Feb 2009
Last updated
11 Jun 2021
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Lee KC, Lew R, Weinstock MA. Improvement in precision of counting actinic keratoses. Br J Dermatol. 2014 Jan;170(1):188-91. doi: 10.1111/bjd.12629.

    PubMed 24102420

  • Korgavkar K, Firoz EF, Xiong M, Lew R, Marcolivio K, Burnside N, Dyer R, Weinstock MA; VAKCC Trial Group. Measuring the severity of topical 5-fluorouracil toxicity. J Cutan Med Surg. 2014 Jul-Aug;18(4):229-35. doi: 10.2310/7750.2013.13143.

    PubMed 25008439

  • Pomerantz H, Hogan D, Eilers D, Swetter SM, Chen SC, Jacob SE, Warshaw EM, Stricklin G, Dellavalle RP, Sidhu-Malik N, Konnikov N, Werth VP, Keri J, Lew R, Weinstock MA; Veterans Affairs Keratinocyte Carcinoma Chemoprevention (VAKCC) Trial Group. Long-term Efficacy of Topical Fluorouracil Cream, 5%, for Treating Actinic Keratosis: A Randomized Clinical Trial. JAMA Dermatol. 2015 Sep;151(9):952-60. doi: 10.1001/jamadermatol.2015.0502.

    PubMed 25950503

  • Chen SC, Hill ND, Veledar E, Swetter SM, Weinstock MA. Reliability of quantification measures of actinic keratosis. Br J Dermatol. 2013 Dec;169(6):1219-22. doi: 10.1111/bjd.12591.

    PubMed 24033340

  • Pomerantz H, Korgavkar K, Lee KC, Lew R, Weinstock MA; VAKCC Trial Group. Validation of Photograph-Based Toxicity Score for Topical 5-Fluorouracil Cream Application. J Cutan Med Surg. 2016 Sep;20(5):458-66. doi: 10.1177/1203475416643952. Epub 2016 Apr 18.

    PubMed 27207349

  • Siegel JA, Luber AJ, Weinstock MA; Department of Veterans Affairs Topical Tretinoin Chemoprevention Trial and Department of Veterans Affairs Keratinocyte Carcinoma Chemoprevention Trial Groups. Predictors of actinic keratosis count in patients with multiple keratinocyte carcinomas: A cross-sectional study. J Am Acad Dermatol. 2017 Feb;76(2):346-349. doi: 10.1016/j.jaad.2016.09.020. No abstract available.

    PubMed 28088997

  • Walker JL, Siegel JA, Sachar M, Pomerantz H, Chen SC, Swetter SM, Dellavalle RP, Stricklin GP, Qureshi AA, DiGiovanna JJ, Weinstock MA. 5-Fluorouracil for Actinic Keratosis Treatment and Chemoprevention: A Randomized Controlled Trial. J Invest Dermatol. 2017 Jun;137(6):1367-1370. doi: 10.1016/j.jid.2016.12.029. No abstract available.

    PubMed 28532759

  • Pomerantz H, Chren MM, Lew R, Weinstock MA; VA Keratinocyte Carcinoma Chemoprevention (VAKCC) Trial Group*. Validation and comparison of quality-of-life measures for topical 5-fluorouracil treatment: results from a randomized controlled trial. Clin Exp Dermatol. 2017 Jul;42(5):488-495. doi: 10.1111/ced.13089.

    PubMed 28621489

  • Korgavkar K, Weinstock MA, Lee KC; VAKCC Trial Group. Evaluation of photoaging scales in an elderly male population. J Eur Acad Dermatol Venereol. 2017 Nov;31(11):e489-e490. doi: 10.1111/jdv.14330. Epub 2017 Jun 20. No abstract available.

    PubMed 28500658

  • Leader NF, Means AD, Robinson-Bostom L, Telang GH, Wilkel CS, Weinstock MA; Veterans Affairs Keratinocyte Carcinoma Chemoprevention Trial group. Interrater reliability for histopathologic diagnosis of keratinocyte carcinomas. J Am Acad Dermatol. 2018 Jan;78(1):185-187. doi: 10.1016/j.jaad.2017.07.024. No abstract available.

    PubMed 29241779

  • Korgavkar K, Lee KC, Weinstock MA; Veterans Affairs Keratinocyte Carcinoma Chemoprevention (VAKCC) Trial Group. Effect of Topical Fluorouracil Cream on Photodamage: Secondary Analysis of a Randomized Clinical Trial. JAMA Dermatol. 2017 Nov 1;153(11):1142-1146. doi: 10.1001/jamadermatol.2017.2578.

    PubMed 28877312

  • Means AD, Lee KC, Korgavkar K, Swetter SM, Dellavalle RP, Chen S, Stricklin G, Weinstock MA; Veterans Affairs Keratinocyte Carcinoma Chemoprevention (VAKCC) Trial Group. Development of a Pigmented Facial Lesion Scale Based on Darkness and Extent of Lesions in Older Veterans. J Invest Dermatol. 2019 May;139(5):1185-1187. doi: 10.1016/j.jid.2018.11.017. Epub 2018 Nov 30. No abstract available.

    PubMed 30508548

  • Beatson M, Means AD, Leader NF, Robinson-Bostom L, Weinstock MA. Characteristics of Keratinocyte Carcinomas and Patients with Keratinocyte Carcinomas Following a Single 2-4 Week Course of Topical 5-fluorouracil on the Face and Ears. Acta Derm Venereol. 2019 Jun 1;99(7):707-708. doi: 10.2340/00015555-3176. No abstract available.

    PubMed 30896781

  • Beatson M, Siegel JA, Chren MM, Weinstock MA. Effects of increased actinic keratosis count on skin-related quality of life: results from the Veterans Affairs Keratinocyte Carcinoma Chemoprevention (VAKCC) Trial. Eur J Dermatol. 2019 Oct 1;29(5):507-510. doi: 10.1684/ejd.2019.3637.

    PubMed 31647464

  • Beatson M, Misitzis A, Landow S, Yoon J, Higgins HW 2nd, Phibbs C, Weinstock MA. Predictors of Basal Cell Carcinoma and Implications for Follow-Up in High-Risk Patients in the Veterans Affairs Keratinocyte Carcinoma Chemoprevention (VAKCC) Trial. J Cutan Med Surg. 2021 Jan-Feb;25(1):102-103. doi: 10.1177/1203475420945230. Epub 2020 Sep 3. No abstract available.

    PubMed 32880186

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing 5-fluorouracil in people with Carcinoma, Basal Cell and Carcinoma, Squamous Cell, run by VA Office of Research and Development at 13 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 Mar 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The Time to Diagnosis of the First Keratinocyte Carcinoma (KC) on the Face or Ears for Which Surgery is Performed (time frame: From randomization to last visit prior to end of study date (6/30/2013), assessed up to four years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00847912, which also lists 19 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jun 2021; AzTrials last refreshed its copy on 8 Nov 2026.

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