CSP #562 - The VA Keratinocyte Carcinoma Chemoprevention Trial
Condition: Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Skin Neoplasms; Skin Diseases; Neoplasms, Basal Cell; Neoplasms, Squamous Cell; Carcinoma
MeSH terms: Carcinoma; Neoplasms; Carcinoma, Squamous Cell; Skin Neoplasms; Carcinoma, Basal Cell; Neoplasms, Squamous Cell; Neoplasms, Basal Cell; Skin Diseases
Intervention: 5-fluorouracil; Placebo, vehicle control
Intervention description: 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.; 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.
Intervention MeSH terms: Fluorouracil
Phase: Phase 4
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 954.0
Sex: All
Healthy volunteers: No
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

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.
    

Eligibility 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. 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:

          -  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.