Actinic Keratoses
Conditions
Keywords
Combination treatment, Imiquimod, Cryotherapy
Brief summary
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.
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.
Interventions
1 packet (250 mg cream) 3 times per week for 4 weeks
Sponsors
Rigel Dermatology
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Actinic Keratoses Count at 4-8 Weeks Post-treatment | Baseline, 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cosmetic Appearance Score at 4-8 Weeks Post-treatment | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Local Skin Reactions | Post baseline to end of study (4-8 weeks post-treatment) | 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. |
Countries
United States
Participant flow
Recruitment details
First patient enrolled - 08 Oct 08; last patient enrolled - 07 Jul 09; last patient completed: 09 Sep 09; Setting - private practice clinics
Participants by arm
| Arm | Count |
|---|---|
| Cryotherapy Followed by Imiquimod 5% Cream or Observation Split-face study of cryotherapy of all actinic keratoses in target treatment area (bilaterally symmetrical area on face or balding scalp) followed by random assignment to treatment of half of treatment area with imiquimod 5% cream and of other half to no treatment | 27 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 1 |
Baseline characteristics
| Characteristic | Cryotherapy Followed by Imiquimod 5% Cream or Observation |
|---|---|
| Actinic keratoses, Imiquimod side | 8.7 Lesions STANDARD_DEVIATION 2.2 |
| Actinic keratoses, Observation Side | 8.5 Lesions STANDARD_DEVIATION 2.3 |
| Actinic keratoses, total | 17.3 Lesions STANDARD_DEVIATION 4.1 |
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 17 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants |
| Age, Continuous | 67.8 years STANDARD_DEVIATION 9.2 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 26 Participants |
| Region of Enrollment United States | 27 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 3 / 27 |
| serious Total, serious adverse events | 0 / 27 |
Outcome results
Primary
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.
Time frame: Baseline, 4-8 weeks post-treatment
Population: Patients who had end of study visit with count of actinic keratoses. Change not calculated for one patient who was lost to follow-up immediately after baseline visit, and had no post-treatment data. Actinic keratoses at 4-8 weeks post-treatment visit includes all actinic keratoses in each respective treatment area, baseline or new.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cryotherapy Followed by Imiquimod 5% Cream or Observation | Change From Baseline in Actinic Keratoses Count at 4-8 Weeks Post-treatment | Change from baseline, imiquimod side | -73.2 Percent change | Standard Deviation 27.1 |
| Cryotherapy Followed by Imiquimod 5% Cream or Observation | Change From Baseline in Actinic Keratoses Count at 4-8 Weeks Post-treatment | Change from baseline, observation side | -62.0 Percent change | Standard Deviation 30.3 |
Secondary
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.
Time frame: 4-8 weeks post-treatment
Population: Patients who had end of study visit with cosmetic appearance assessment. Cosmetic appearance score, by treatment area, not included for one patient who was lost to follow-up immediately after baseline visit, and had no post-treatment data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cryotherapy Followed by Imiquimod 5% Cream or Observation | Cosmetic Appearance Score at 4-8 Weeks Post-treatment | Investigator assessed, imiquimod side | 2.1 Scores on a scale | Standard Deviation 1.1 |
| Cryotherapy Followed by Imiquimod 5% Cream or Observation | Cosmetic Appearance Score at 4-8 Weeks Post-treatment | Investigator assessed, observation side | 1.6 Scores on a scale | Standard Deviation 1.1 |
| Cryotherapy Followed by Imiquimod 5% Cream or Observation | Cosmetic Appearance Score at 4-8 Weeks Post-treatment | Patient assessed, imiquimod side | 2.6 Scores on a scale | Standard Deviation 1 |
| Cryotherapy Followed by Imiquimod 5% Cream or Observation | Cosmetic Appearance Score at 4-8 Weeks Post-treatment | Patient assessed, observation side | 1.2 Scores on a scale | Standard Deviation 1.3 |
Post Hoc
Complete Clearance of Actinic Keratoses at 4-8 Weeks Post-treatment
Complete clearance (actinic keratosis count of 0) in each respective area at 4-8 weeks post-treatment. Actinic keratoses at 4-8 weeks post-treatment visit includes all actinic keratoses in each respective treatment area, baseline and new.
Time frame: 4-8 weeks post-treatment
Population: All patients enrolled.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cryotherapy Followed by Imiquimod 5% Cream or Observation | Complete Clearance of Actinic Keratoses at 4-8 Weeks Post-treatment | Completely cleared, imiquimod side | 8 Participants |
| Cryotherapy Followed by Imiquimod 5% Cream or Observation | Complete Clearance of Actinic Keratoses at 4-8 Weeks Post-treatment | Completely cleared, observation side | 5 Participants |
Other Pre-specified
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.
Time frame: Post baseline to end of study (4-8 weeks post-treatment)
Population: One patient not included who was lost to follow-up immediately after baseline visit, and had no post-treatment data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cryotherapy Followed by Imiquimod 5% Cream or Observation | Local Skin Reactions | Erythema, imiquimod side | 1.5 Scores on a scale | Standard Deviation 0.7 |
| Cryotherapy Followed by Imiquimod 5% Cream or Observation | Local Skin Reactions | Erythema, observation side | 1.3 Scores on a scale | Standard Deviation 0.5 |
| Cryotherapy Followed by Imiquimod 5% Cream or Observation | Local Skin Reactions | Edema, imiquimod side | 0.2 Scores on a scale | Standard Deviation 0.4 |
| Cryotherapy Followed by Imiquimod 5% Cream or Observation | Local Skin Reactions | Edema, observation side | 0.1 Scores on a scale | Standard Deviation 0.3 |
| Cryotherapy Followed by Imiquimod 5% Cream or Observation | Local Skin Reactions | Weeping/exudate, imiquimod side | 0.3 Scores on a scale | Standard Deviation 0.7 |
| Cryotherapy Followed by Imiquimod 5% Cream or Observation | Local Skin Reactions | Weeping/exudate, observation side | 0.0 Scores on a scale | Standard Deviation 0 |
| Cryotherapy Followed by Imiquimod 5% Cream or Observation | Local Skin Reactions | Flaking/scaling/dryness, imiquimod side | 1.4 Scores on a scale | Standard Deviation 0.6 |
| Cryotherapy Followed by Imiquimod 5% Cream or Observation | Local Skin Reactions | Flaking/scaling/dryness, observation side | 1.2 Scores on a scale | Standard Deviation 0.6 |
| Cryotherapy Followed by Imiquimod 5% Cream or Observation | Local Skin Reactions | Scabbing/crusting, imiquimod side | 0.9 Scores on a scale | Standard Deviation 1.1 |
| Cryotherapy Followed by Imiquimod 5% Cream or Observation | Local Skin Reactions | Scabbing/crusting, observation side | 0.6 Scores on a scale | Standard Deviation 0.7 |
| Cryotherapy Followed by Imiquimod 5% Cream or Observation | Local Skin Reactions | Erosion/ulceration, imiquimod side | 0.4 Scores on a scale | Standard Deviation 0.7 |
| Cryotherapy Followed by Imiquimod 5% Cream or Observation | Local Skin Reactions | Erosion/ulceration, observation side | 0.1 Scores on a scale | Standard Deviation 0.4 |