Actinic Keratosis
Conditions
Keywords
Wake Forest, Actinic Keratosis, Cryosurgery, Cream
Brief summary
Carac 0.5% cream is approved for daily topical treatment of AK's for up to four weeks as tolerated, though local irritation often occurs within the first week of treatment and increases in a dose-dependent manner. In this study, the investigators will examine the combination of standard cryosurgery treatment followed by a shortened course of topical fluorouracil cram. The investigators anticipate that a one week treatment course will maintain overall effectiveness when combined with previous cryosurgery, but will reduce the overall adverse effects of topical therapy due to the reduced treatment time and the presence of fewer baseline lesions to treat. This treatment approach may provide a more acceptable risk/benefit ratio option for patients with more extensive disease and simplify standard combination treatment options. The primary objective is to evaluate the efficacy of combination cryosurgery and 5-fluorouracil0.5% cream, compared to combination cryosurgery and placebo in the treatment of actinic keratosis lesions. The efficacy of this combination therapy will be evaluated by assessing AK lesion clearance. The primary efficacy parameter will be 10% clearance of all AK lesions from treatment initiation to end-of-treatment.
Detailed description
This is a randomized (1:1), single-blind, placebo controlled, single center prospective study. Subjects will first undergo cryosurgery of all clinically apparent AK lesions, limited to the face or balding scalp. Three weeks after cryosurgery, subjects will then be randomized (1:1 according to standard randomization tables) and directed to apply either Carac 0.5% cream or placebo cream (Cetaphil Cream) to the face or balding scalp at bedtime for seven consecutive days, washed off each following morning. Each does of study cream will be applied at approximately the same time of day and will remain on the skin for approximately eight hours. Subject evaluation, Investigator Global Assessments, Quality of Life lesion counts and photography shall be performed at Baseline. At Week 3, study drug will be dispensed and the global assessments and assessment of improvement will be performed. A Medication Tolerability Assessment will occur at Week 4 when the study drug will be returned. Investigator Global Assessment, lesion count, Global Assessment of Improvement and Quality of Life will be measured at Week 8 and Week 26 (or end of study). Photography will be done at Week 26 or end of study.
Interventions
DRUGCarac Cream
Carac Cream will be used once daily for seven consecutive days
DRUGPlacebo Cetaphil cream
Placebo Cetaphil Cream will be used once daily for seven consecutive days
Sponsors
Wake Forest University Health Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* Must be male or female and at least 18 years of age. Each subject must demonstrate good health as determined by a baseline medical history. * Female subjects myst be of either non-childbearing potential, or childbearing potential provided: negative urine pregnancy test and using two acceptable methods of effective contraception (abstinence, birth control pills.patch, DepoProvera, tubal ligation, vasectomy of the partner in a monogamous relationship, condoms and spermicidal form or gel and/or cervical cap or sponge), as determined by the investigator * At least eight clinically typical, visible and discrete AK lesions within the treatment area on the face or balding scalp * Subjects must be able and willing to comply with study procedures and have provided written informed consent.
Exclusion criteria
* Cosmetic or therapeutic procedures (e.g., use of liquid nitrogen, surgical excision, curettage, dermabrasion, medium or greater depth chemical peel, laser resurfacing) within the selected treatment area in the previous four weeks. * Treatment with systemic medications that suppress the immune system within the previous four weeks. * Field treatments with topical 5-FU, imiquimod, diclofenac, or photodynamic therapy, or more widespread field treatment with dermabrasion, medium or greater depth chemical peel, or laser resurfacing within the previous six months. * Any known dihydropyrimidine dehydrogenase enzyme deficiency. * In addition, subjects who have any skin condition or disease that may require concurrent therapy or may confound the evaluation as determined by the investigator, or a history of hypersensitivity to any of the formulation components will be excluded from study. * Subjects may not use other topical agents such as glycolic acid products, alpha-hydroxy acid products, retinoids and chemical peel agents on teh treatment area while on study. The use of these products are not allowed four weeks prior to study enrollment. Introduction of any other prescription medication, topical or systemic for actinic keratosis while participating in the study is not permitted. * Pregnant women, women who are breast feeding, or women of childbearing potential who are not practicing two acceptable methods of effective contraception.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number Participants With 100% Clearance | 24 weeks | The primary endpoint is number of participants that receive 100% clearance of AK lesions from treatment initiation to end of treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With 75% Clearance | 24 weeks | The secondary endpoint is number of participants that receive 75 % clearance of |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group 1 Carac (Fluorouracil) 0.5% Cream Carac cream (fluorouracil) 0.5% applied daily on the face for one week
Carac Cream: Carac Cream will be used once daily for seven consecutive days | 30 |
| Group 2 Placebo Placebo Cetaphil cream applied daily on the face for one week
Placebo Cetaphil cream: Placebo Cetaphil Cream will be used once daily for seven consecutive days | 30 |
| Total | 60 |
Baseline characteristics
| Characteristic | Group 1 Carac (Fluorouracil) 0.5% Cream | Group 2 Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 21 Participants | 22 Participants | 43 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants | 8 Participants | 17 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 30 Participants | 29 Participants | 59 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 30 Participants | 30 Participants | 60 Participants |
| Region of Enrollment United States | 30 participants | 30 participants | 60 participants |
| Sex: Female, Male Female | 3 Participants | 2 Participants | 5 Participants |
| Sex: Female, Male Male | 27 Participants | 28 Participants | 55 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 30 | 0 / 30 |
| other Total, other adverse events | 4 / 30 | 5 / 30 |
| serious Total, serious adverse events | 0 / 30 | 0 / 30 |
Outcome results
Primary
Number Participants With 100% Clearance
The primary endpoint is number of participants that receive 100% clearance of AK lesions from treatment initiation to end of treatment
Time frame: 24 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group 1 Carac (Fluorouracil) 0.5% Cream | Number Participants With 100% Clearance | 12 Participants |
| Group 2 Placebo | Number Participants With 100% Clearance | 13 Participants |
Secondary
Number of Participants With 75% Clearance
The secondary endpoint is number of participants that receive 75 % clearance of
Time frame: 24 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group 1 Carac (Fluorouracil) 0.5% Cream | Number of Participants With 75% Clearance | 18 Participants |
| Group 2 Placebo | Number of Participants With 75% Clearance | 16 Participants |