Topical Imiquimod Cream in Combination With Cryotherapy for the Treatment of Actinic Keratoses

A Randomized, Open-label, Assessor-blinded, Split-face Study of Imiquimod 5% Cream Applied After Cryotherapy of Actinic Keratoses

The purpose of this study is to determine if use of topical imiquimod cream after cryotherapy of actinic keratoses reduces the total number of lesions (those treated with cryotherapy and new ones) at follow-up.

Actinic keratoses are common skin lesions associated with excess sun exposure. Over time, there is a small risk a lesion may progress to skin cancer. Since one can not predict which actinic keratosis will progress, the standard of care is to treat the lesions. The most commonly used method to treat actinic keratoses in the United States is with cryotherapy, which uses intense cold to freeze and destroy the lesions. Efficacy appears to be related to how long one freezes the lesion, but increasing the freeze time may result in increased pain and/or skin pigment changes after treatment.

Cryotherapy is a provider-administered "focal" treatment that only treats the lesions that are frozen. There may be early actinic keratoses in the skin surrounding treated lesions that are not easily seen; these may progress over time to visible lesions. There several patient-administered topical treatments for actinic keratoses that are applied to a treatment area or "field" rather than to specific lesions. Imiquimod 5% cream is one such treatment, and is approved in the United States for the treatment of AKs with a dosing regimen of 1 packet applied 2 times per week to a 25 cm2 area 2x/week for 16 weeks.

The study will use a split-face design (one side of face treated and the other side untreated) to explore whether a 4-week course of topical imiquimod 5% cream after cryotherapy of actinic keratoses reduces the total number of lesions (those treated with cryotherapy and new ones) in the treatment area at follow-up.

Inclusion Criteria:

• A clinical diagnosis of actinic keratoses

• Actinic keratoses in two reasonably bilaterally symmetric areas on the face and/or balding scalp:

  • each area with a minimum of 25 cm^2 and a maximum of 50 cm^2
  • each area with at least 6 typical, non-hypertrophic target AKs
  • with target AK lesion counts of +/- 1 lesion between the areas
  • each area that the patient can distinguish with respect to study drug application

• Able to comply with all study requirements

• Are willing and able to give written informed consent

Exclusion Criteria:

• Uncontrolled intercurrent or chronic illness

• Systemic immunocompromise due to disease or treatment

• Clinically relevant systemic autoimmune disease

• Pregnant or nursing

• Dermatologic disease and/or condition in the treatment area that may be exacerbated by imiquimod or cause difficulty with examination

• Participation in another clinical study

• Allergies to imiquimod or any of the excipients in the cream

• Treatment within the past 90 days with any of the following:

  • Psoralens plus ultraviolet A therapy
  • Ultraviolet B therapy
  • Systemic immunomodulators (e.g. oral or parenteral corticosteroids at greater than physiologic doses, interferons, anti-TNF agents, cytokines)
  • Chemotherapeutic or cytotoxic agents;
  • Investigational agent

• Treatment within the past 30 days with any of the following:

  • Surgical excision
  • Photodynamic therapy
  • Curettage
  • Topical corticosteroids
  • Laser
  • Dermabrasion
  • Chemical peel
  • Imiquimod 5% cream
  • Topical retinoids
  • 5-fluorouracil
  • Masoprocol
  • Pimecrolimus or tacrolimus