Treatment of Actinic Keratoses of the Face With Imiquimod 3.75% Cream Followed by Photodynamic Therapy

An Exploratory, Open-label Study of Sequential Field-directed Treatment of Actinic Keratoses of the Face With Imiquimod 3.75% Cream Followed by Photodynamic Therapy

The purpose of this study is to explore the effect of treating actinic keratoses of the face with imiquimod 3.75% cream followed by photodynamic therapy in comparison to treatment with imiquimod alone

Study Overview

• Status: Terminated
• Conditions: Actinic Keratosis
• Intervention / Treatment: Drug: Photodynamic therapy; Drug: Imiquimod

Detailed Description

Actinic keratoses are common skin lesions associated with solar ultraviolet radiation exposure. Some actinic keratoses may develop into skin cancers.

Imiquimod 3.75% cream is an approved treatment for actinic keratoses that utilizes a regimen of application to the entire face or balding scalp of up to 2 packets of cream daily for two 2-week cycles, separated by a 2-week no treatment interval.

Photodynamic therapy with aminolevulinic acid (ALA) 20% topical solution is also an approved treatment for actinic keratoses. ALA is applied to actinic keratoses, and after an incubation period, is excited with light. Although approved as a lesion-directed treatment for actinic keratoses, treatment of a field (e.g. face) with photodynamic therapy is commonly performed.

Treatment with photodynamic therapy followed by imiquimod 5% cream has been reported in patients with actinic keratoses, basal cell carcinoma and Bowen's disease, and treatment with imiquimod 5% cream followed by photodynamic therapy in patients with vulvar intraepithelial neoplasia. There are, however, no prior studies on the safety and/or efficacy of using topical imiquimod 3.75% in conjunction with photodynamic therapy in the treatment of actinic keratoses.

This study will use an open-label parallel cohort design in which all patients will received treatment with imiquimod 3.75% cream, and subsequently will be randomized to either photodynamic therapy or observation.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Englewood, Colorado, United States, 80113
      • AboutSkin Dermatology and DermSurgery, PC
  • North Carolina
    • Charlotte, North Carolina, United States, 28207
      • Dermatology, Laser & Vein Specialists of the Carolinas
  • Tennessee
    • Nashville, Tennessee, United States, 37215
      • Tennessee Clinical Research Center

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:

• Male and female adults; 18 and over
• At least 10 and no more than 30 clinically typical actinic keratoses on the face

Exclusion Criteria:

• Hypertrophic actinic keratoses or other skin lesions on the head that might required excluded treatment during the study
• Known contraindication to treatment with imiquimod or photodynamic therapy
• Condition that would limit compliance, be a potential safety risk, or require therapy with an excluded treatment
• Systemically immunocompromised
• Pregnant or nursing
• Dermatologic disease and/or condition in treatment area that might exacerbated by treatment with imiquimod, cause difficulty with examination, or require therapy with an excluded treatment
• Participation in another clinical study

• Treatment within the past 60 days with:

  • Ultraviolet therapy
  • Systemic immunomodulators
  • Chemotherapeutic or cytotoxic agents
  • Investigational agents

• Treatment on the head within the past 60 days with:

  • Imiquimod
  • Photodynamic therapy
  • Red or blue light source therapy
  • Cryotherapy or chemotherapy
  • Surgical excision or curettage
  • Topical corticosteroids
  • Laser
  • Dermabrasion
  • Chemical peel
  • Topical retinoids
  • Topical 5-fluorouracil
  • Topical pimecrolimus or tacrolimus
  • Topical diclofenac
• Treatment for actinic keratoses on the head within the past 60 days

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Imiquimod & photodynamic therapy; Imiquimod 3.75% applied to the entire face daily for 2 2-week cycles separated by a 2-week no treatment period, followed by one session of photodynamic therapy of the entire face with aminolevulinic acid and blue light	Drug: Photodynamic therapy; Administered 4 weeks after completion of imiquimod therapy; Other Names: Levulan Kerasticks (aminolevulinic acid 20% solution); Drug: Imiquimod; Imiquimod 3.75% cream, up to 2 packets, applied topically daily for two 2-week cycles separated by a no-treatment interval of 2-weeks, followed observation; Other Names: Zyclara (imiquimod 3.75% cream)
ACTIVE_COMPARATOR: Imiquimod; Imiquimod 3.75% applied to the entire face daily for 2 2-week cycles separated by a 2-week no treatment period, followed by observation	Drug: Imiquimod; Imiquimod 3.75% cream, up to 2 packets, applied topically daily for two 2-week cycles separated by a no-treatment interval of 2-weeks, followed observation; Other Names: Zyclara (imiquimod 3.75% cream)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Actinic Keratosis Count	The percent change in actinic keratosis count as compared to the baseline lesion count	Week 18 (4 weeks after randomization visit)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Clearance	The proportion of randomized patients with complete clearance of actinic keratoses in the treatment area (entire face).	Week 18 (4 weeks after randomization visit)
Cosmetic Appearance	Change (improvement) in investigator scores of cosmetic appearance of the treatment area (entire face) by objective and subjective assessments: INVESTIGATOR COSMETIC ASSESSMENT 0 - Facial skin is smooth to the touch, without significant lines or unevenness in pigmentation 1 - Facial skin shows 1 area (cheeks, forehead, or the perioral area) of significant 3 - Facial skin shows 3 areas with significant roughness, dyspigmentation, or fine lines 2 - Facial skin shows 2 areas of significant roughness, dyspigmentation, or fine lines 4 - All are severe in severity	Week 18 (4 weeks after randomization visit)

Collaborators and Investigators

• Sponsor: Tennessee Clinical Research Center
• Collaborators: Graceway Pharmaceuticals, LLC
• Investigators: Study Chair: Michael Gold, MD, Tennessee Clinical Research Center; Principal Investigator: Joel Cohen, MD, AboutSkin Dermatology and DermSurgery, PC

Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (ACTUAL): November 1, 2011
• Study Completion (ACTUAL): November 1, 2011

Study Registration Dates

• First Submitted: September 15, 2010
• First Submitted That Met QC Criteria: September 15, 2010
• First Posted (ESTIMATE): September 17, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): December 8, 2014
• Last Update Submitted That Met QC Criteria: November 20, 2014
• Last Verified: November 1, 2014

More Information

Terms related to this study

• Keywords: Sequential therapy; Photodynamic therapy; Imiquimod; Actinic keratoses; Therapeutic uses
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Precancerous Conditions; Keratosis, Actinic; Keratosis; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Photosensitizing Agents; Dermatologic Agents; Adjuvants, Immunologic; Interferon Inducers; Aminolevulinic Acid; Imiquimod
• Other Study ID Numbers: 09US05N375-Gold