Clinical trial NCT02242747: Safety and Tolerability Study of Ingenol Mebutate Compared to 5-FU to Treat Facial Actinic Keratosis
Official title: Evaluation of the Tolerability and Safety of 0.015% Ingenol Mebutate Gel Compared to 5% 5-fluorouracil Cream for the Treatment of Facial Actinic Keratosis: a Prospective Randomized Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Actinic Keratosis
Keywords: actinic keratosis
field cancerization
ingenol mebutate
5-fluorouracil
tolerability
safety
Lead sponsor: University of Sao Paulo
Sponsor class: OTHER
Collaborators: name: LEO Pharma
First posted: 2014-09-17
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Background: 5% 5-fluorouracil cream (5-FU) is a well-established treatment for actinic keratosis (AK) and ingenol mebutate gel (IMB) is a new topical field therapy.

Objective: To compare tolerability and safety of IMB with 5-FU for the treatment of facial AKs.

Methods: Open-label, prospective, randomized, controlled clinical trial with 100 patients with AKs within 25-cm2 contiguous field on the face. IMB was applied daily for three consecutive days. 5-FU was applied twice a day for four weeks. Treatment effect was evaluated at baseline and on days 2, 3, 4, 8, 15, 22, 29, 36 and 43, considering ITT populations.


Eligibility criteria: Inclusion Criteria:

* age of at least 18 years
* the presence of four to eight clinically typical, visible, and discrete AKs within 25-cm2 contiguous field on the face (cheek or forehead region)
* Women with childbearing potential had to be using effective birth control and have a confirmed negative urine pregnancy test prior to trial treatment.

Exclusion Criteria:

* target treatment area was within 5 cm of an incompletely healed wound or within 10 cm of a suspected basal-cell or squamous-cell carcinoma
* if they have received previous treatment with ingenol mebutate gel on the face or scalp (previous treatment on trunk or extremities was acceptable)
* the selected treatment area had hyperkeratotic lesions or cutaneous horns and recalcitrant disease (lesions that had not responded to cryotherapy on two previous occasions)
* history or evidence of skin conditions that would interfere with the evaluation of the trial medication (e.g., eczema, unstable psoriasis, xeroderma pigmentosum)
* anticipated need for hospitalization or outpatient surgery during the first 15 days after the first trial medication application
* known sensitivity or allergy to any of the ingredients of ingenol mebutate gel or 5-FU
* presence of sunburn within of the target treatment area; current enrolment or participation in any other interventional clinical trial within 30 days of entry into this trial
* women breastfeeding
* recent use of medications or other treatments that could interfere with evaluation of the target area, such as topical medications (e.g. steroids, keratolytics, immunomodulators), artificial tanners, immunomodulators, cytotoxic drugs or interferon /interferon inducers, phototherapy, systemic retinoids, biologic/monoclonal antibody drugs, or other therapies for AKs within eight weeks prior to the first visit of the trial.

Primary outcomes:
measure: Area under the LSR (local skin reactions)-Time Curve (AUC 0-43 days)
timeFrame: Baseline and on day 43
Secondary outcomes:
measure: Area Under the each component of the total LSR-Time Curve (AUC 0-43 days)
timeFrame: Baseline and on day 43
Other outcomes:
measure: Number of participants with side effects in each arm of the study
timeFrame: Baseline and on day 43
Locations:
city: Sao Paulo
country: Brazil
facility: Hospital das Clínicas of the University of São Paulo Medical School (HCFMUSP)
Study officials:
affiliation: Hospital das Clínicas of the University of São Paulo Medical School (HCFMUSP)
name: Luis Antonio Torezan, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Samorano LP, Torezan LA, Sanches JA. Evaluation of the tolerability and safety of a 0.015% ingenol mebutate gel compared to 5% 5-fluorouracil cream for the treatment of facial actinic keratosis: a prospective randomized trial. J Eur Acad Dermatol Venereol. 2015 Sep;29(9):1822-7. doi: 10.1111/jdv.13063. Epub 2015 Feb 27.