CSP #562 - The VA Keratinocyte Carcinoma Chemoprevention Trial

NCT00847912 | Completed Phase 4 Results DMC FDA Drug

• 1 other identifier: 562
• Study Type: interventional
• Target: 954
• Locations: 1 country
• Sites: 13

Brief 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. 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. 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.

Conditions

Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Skin Neoplasms; Skin Diseases; Neoplasms, Basal Cell; Neoplasms, Squamous Cell; Carcinoma

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

Outcome Measures

Primary Outcomes (2)

• 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.

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

• Hazard Ratio for Surgically Treated KC

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

Study Arms (2)

Arm 1: 5-fluorouracil

EXPERIMENTAL

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

Drug: 5-fluorouracil

Arm 2: Placebo

PLACEBO COMPARATOR

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

Drug: Placebo, vehicle control

Interventions

5-fluorouracil DRUG

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.

Also known as: Efudex, 5-FU

Arm 1: 5-fluorouracil

Placebo, vehicle control DRUG

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.

Also known as: Placebo

Arm 2: Placebo

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.
• 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.
• 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).

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (13)

VA Palo Alto Health Care System, Palo Alto, CA

Palo Alto, California, 94304-1290, United States

Location

VA San Diego Healthcare System, San Diego, CA

San Diego, California, 92161, United States

Location

VA Eastern Colorado Health Care System, Denver, CO

Denver, Colorado, 80220, United States

Location

Bay Pines VA Healthcare System, Pay Pines, FL

Bay Pines, Florida, 33744, United States

Location

Miami VA Healthcare System, Miami, FL

Miami, Florida, 33125, United States

Location

Atlanta VA Medical and Rehab Center, Decatur, GA

Decatur, Georgia, 30033, United States

Location

Edward Hines Jr. VA Hospital, Hines, IL

Hines, Illinois, 60141-5000, United States

Location

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

Boston, Massachusetts, 02130, United States

Location

Minneapolis VA Health Care System, Minneapolis, MN

Minneapolis, Minnesota, 55417, United States

Location

Durham VA Medical Center, Durham, NC

Durham, North Carolina, 27705, United States

Location

Philadelphia VA Medical Center, Philadelphia, PA

Philadelphia, Pennsylvania, 19104, United States

Location

Providence VA Medical Center, Providence, RI

Providence, Rhode Island, 02908, United States

Location

Tennessee Valley Healthcare System Nashville Campus, Nashville, TN

Nashville, Tennessee, 37212-2637, United States

Location

Related Publications (19)

• 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.

  PMID: 24102420 BACKGROUND

• 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.

  PMID: 25008439 BACKGROUND

• 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.

  PMID: 25950503 BACKGROUND

• 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.

  PMID: 24033340 BACKGROUND

• 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.

  PMID: 27207349 RESULT

• 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.

  PMID: 28088997 RESULT

• 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.

  PMID: 28532759 RESULT

• 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.

  PMID: 28621489 RESULT

• 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.

  PMID: 28500658 RESULT

• 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.

  PMID: 29241779 RESULT

• 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.

  PMID: 28877312 RESULT

• 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.

  PMID: 30508548 RESULT

• 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.

  PMID: 30896781 RESULT

• 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.

  PMID: 31647464 RESULT

• 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.

  PMID: 32880186 RESULT

• Misitzis A, Stratigos AJ, Beatson M, Mastorakos G, Dellavalle RP, Weinstock MA; Veterans Affairs Keratinocyte Carcinoma Chemoprevention Trial Group. The association of metformin use with keratinocyte carcinoma development in high-risk patients. Dermatol Ther. 2020 Nov;33(6):e14402. doi: 10.1111/dth.14402. Epub 2020 Oct 20.

  PMID: 33047438 RESULT

• Siegel JA, Chren MM, Weinstock MA; Department of Veterans Affairs Keratinocyte Carcinoma Chemoprevention Trial Group. Correlates of skin-related quality of life (QoL) in those with multiple keratinocyte carcinomas (KCs): A cross-sectional study. J Am Acad Dermatol. 2016 Sep;75(3):639-642. doi: 10.1016/j.jaad.2016.05.008. No abstract available.

  PMID: 27543222 RESULT

• Yoon J, Phibbs CS, Chow A, Pomerantz H, Weinstock MA. Costs of Keratinocyte Carcinoma (Nonmelanoma Skin Cancer) and Actinic Keratosis Treatment in the Veterans Health Administration. Dermatol Surg. 2016 Sep;42(9):1041-7. doi: 10.1097/DSS.0000000000000820.

  PMID: 27465252 RESULT

• Weinstock MA, Thwin SS, Siegel JA, Marcolivio K, Means AD, Leader NF, Shaw FM, Hogan D, Eilers D, Swetter SM, Chen SC, Jacob SE, Warshaw EM, Stricklin GP, Dellavalle RP, Sidhu-Malik N, Konnikov N, Werth VP, Keri JE, Robinson-Bostom L, Ringer RJ, Lew RA, Ferguson R, DiGiovanna JJ, Huang GD; Veterans Affairs Keratinocyte Carcinoma Chemoprevention Trial (VAKCC) Group. Chemoprevention of Basal and Squamous Cell Carcinoma With a Single Course of Fluorouracil, 5%, Cream: A Randomized Clinical Trial. JAMA Dermatol. 2018 Feb 1;154(2):167-174. doi: 10.1001/jamadermatol.2017.3631.

  PMID: 29299592 DERIVED

MeSH Terms

Conditions

Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Skin Neoplasms; Skin Diseases; Neoplasms, Basal Cell; Neoplasms, Squamous Cell; Carcinoma; Neoplasms; Neoplasms by Site

Interventions

Fluorouracil

Condition Hierarchy (Ancestors)

Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Martin Weinstock MD, PhD
• Organization: Providence VA mendical Center

Martin.Weinstock@va.gov; Martin_Weinstock_MD@brown.edu

401-457-3333

Study Officials

• Martin A. Weinstock, MD

  Providence VA Medical Center, Providence, RI

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 18, 2009
• First Posted: February 19, 2009
• Study Start: June 26, 2009
• Primary Completion: June 28, 2013
• Study Completion: July 30, 2016
• Last Updated: June 11, 2021
• Results First Posted: March 17, 2017

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (13)