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.

Study Overview

• Status: Completed
• Conditions: Actinic Keratoses
• Intervention / Treatment: Drug: imiquimod 5% cream

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Florida
    • Saint Petersburg, Florida, United States, 33716
      • Spencer Dermatology and Skin Surgery
  • Nevada
    • Henderson, Nevada, United States, 89129
      • James Del Rosso
  • New York
    • New York, New York, United States, 10016
      • Rigel Dermatology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Imiquimod, treatment, topical cream; Imiquimod 5% cream, 1 packet (250 mg cream), applied to left or right treatment area on the face and/or balding scalp	Drug: imiquimod 5% cream; 1 packet (250 mg cream) 3 times per week for 4 weeks; Other Names: Aldara
No Intervention: Control, Untreated; No treatment of treatment area on the other half of the face and/or balding scalp

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Actinic Keratoses Count at 4-8 Weeks Post-treatment	Percent change = [(actinic keratoses count at 4-8 weeks post-treatment)-(actinic keratoses count at baseline)]/(actinic keratoses count at baseline)]*100%. Data from one patient, lost to follow-up immediately after cryotherapy, not included in these analyses. Actinic keratoses at 4-8 weeks post-treatment visit includes all actinic keratoses in each respective treatment area, baseline and new.	Baseline, 4-8 weeks post-treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cosmetic Appearance Score at 4-8 Weeks Post-treatment	Cosmetic appearance score, based recall comparison to appearance at baseline. Seven point scale: +3 = treatment area is much better appearing; +2 = treatment area is moderately better appearing; + 1 = treatment area is slightly better appearing; 0 = treatment area appears same; -1 = treatment area is slightly worse appearing; -2 = treatment area is moderately worse appearing; -3 = treatment area is much worse appearing. Data from one patient, lost to follow-up immediately after cryotherapy, not included in these analyses.	4-8 weeks post-treatment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Local Skin Reactions	Mean maximum post-baseline intensity of investigator assessed local skin reactions (erythema, edema, weeping/exudate, flaking/scaling/dryness, scabbing/crusting, erosion/ulceration) by treatment area. 0 = none, 1 = mild, 2 = moderate, 3 = severe. Data from one patient, lost to follow-up immediately after cryotherapy, not included in these analyses.	Post baseline to end of study (4-8 weeks post-treatment)

Collaborators and Investigators

• Sponsor: Rigel Dermatology
• Investigators: Study Chair: Darrell S Rigel, MD, Rigel Dermatology; Principal Investigator: James Q Del Rosso, DO, Private practice; Principal Investigator: James Spencer, Spencer Dermatology

Study record dates

Study Major Dates

• Study Start: October 1, 2008
• Primary Completion (Actual): March 1, 2010
• Study Completion (Actual): March 1, 2010

Study Registration Dates

• First Submitted: October 16, 2008
• First Submitted That Met QC Criteria: October 16, 2008
• First Posted (Estimate): October 17, 2008

Study Record Updates

• Last Update Posted (Estimate): November 6, 2016
• Last Update Submitted That Met QC Criteria: October 3, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: Combination treatment; Cryotherapy; Imiquimod
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Precancerous Conditions; Keratosis, Actinic; Keratosis; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Adjuvants, Immunologic; Interferon Inducers; Imiquimod
• Other Study ID Numbers: 08US02IMIQ-Rigel