Clinical trial NCT02281682: IM Versus 5-FU Versus IMI Versus MAL-PDT in Treatment of Actinic Keratosis
Official title: Topical Ingenol Mebutate Versus 5% 5-fluorouracil Versus 5% Imiquimod Versus Photodynamic Therapy in Treatment of Actinic Keratosis: a Multi-centre Randomized Efficacy and Cost-effectiveness Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Keratosis, Actinic
Keywords: Keratosis, Actinic
Treatment Outcome
cost-effectiveness
economic evaluation
imiquimod
photodynamic therapy
topical fluorouracil
ingenol mebutate
Lead sponsor: Maastricht University Medical Center
Sponsor class: OTHER
First posted: 2014-11-02
Enrollment: 624
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: A multi-centre randomised controled single blind clinical phase IV trial with the aim to determine the most effective treatment in terms of lesion reduction, costs and patient satisfaction in treatment of actinic keratosis (AK), when comparing topical treatment with photodynamic therapy (PDT), 5% 5-fluorouracil (5-FU) cream, 5% Imiquimod (IMI) cream and ingenol mebutate (IM) gel.

Detailed description: Skin cancer is the most common cancer in Caucasians and therefore a major public health issue. Its incidence is increasing rapidly. Actinic keratosis (AK) is the most prevalent precancerous chronic skin condition. It can transform into squamous cell carcinoma (SCC). AK's generally arise in a skin area that has diffuse precancerous damage, a phenomenon called field cancerization. Because of its precancerous character, it is advised to treat AK and herewith prevent development into SCC. The most frequently used field-directed treatments in the Netherlands are photodynamic therapy (PDT), topical 5% f-fluorouracil (5% 5-FU) and topical 5% Imiquimod (5% IMI). Lately another topical product is approved by Dutch healthcare insurances: Ingenol mebutate (IM). Up to date, which treatment the patient will receive, does not rely on evidence-based-medicine, but generally on the preference of the physician. Current national and international guidelines state no clear recommendations for the best choice of therapy. The aim of this study determine which treatment is the most effective treatment in terms of lesion reduction, costs and patient satisfaction when comparing topical treatment with photodynamic therapy (PDT), 5% 5-fluorouracil (5-FU) cream, 5% Imiquimod (IMI) cream and ingenol mebutate (IM) gel, in treatment of actinic keratosis (AK).

Eligibility criteria: Inclusion Criteria:

* Patients older than 18 years
* Fitzpatrick skintype I-IV
* Clinically confirmed diagnosis of AK
* One joint area of minimal 25 cm2 and maximal 100 cm2 of AK
* Minimum of 5 AK lesions
* AK Olsen grade I-III
* Location: head/neck area

Exclusion Criteria:

* Received any kind of treatment for AK in the past 3 months
* (non)melanoma skin cancer in target area
* Immuno-compromised status
* Use of systemic retinoid in the past 3 months
* Use of immunosuppressant drugs in the past 3 months and / or at time of treatment (such as oral glucocorticoids, cytostatic, antibodies, drug acting on immunophilins, interferon, opioids, Tumor Necrosis Factor (TNF) binding proteins, mycofenolate mofetil (MMF), biologic agents). inhalation corticosteroids / nasal corticosteroids are permitted.
* Porphyria
* Not able to give informed consent
* Allergy to study drugs or peanut/nut/soy products
* Pregnant and breastfeeding women
* Female in child bearing potential not using contraceptive measures, during and till 3 months post-treatment
* Genetic skin cancer disorders
* Not understanding Dutch language

Primary outcomes:
measure: treatment succes
timeFrame: 12 months
Secondary outcomes:
measure: treatment failure
timeFrame: 12 months
measure: Treatment succes at 3 months post treatment
timeFrame: 3 months
measure: complete lesion clearance
timeFrame: 12 months
measure: SCC
timeFrame: 12 months
measure: side effects
timeFrame: 12 months
measure: Cosmetic outcome
timeFrame: 3 and 12 months
measure: patient satisfaction
timeFrame: 12 months
measure: treatment compliance
timeFrame: 3 months
measure: Overall decrease in AK
timeFrame: 3 and 12 months
measure: Cost-effectiveness
timeFrame: 12 months
measure: Investigator Global Improvement Indices
timeFrame: 3 and 12 months
measure: Number of new lesions
timeFrame: 3 and 12 months
Other outcomes:
Locations:
city: Maastricht
country: Netherlands
facility: Maastricht UMC
state: Limburg
Study officials:
affiliation: Maastricht University Hospital
name: Klara Mosterd, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ahmady S, Jansen MHE, Nelemans PJ, Kessels JPHM, Arits AHMM, de Rooij MJM, Essers BAB, Quaedvlieg PJF, Kelleners-Smeets NWJ, Mosterd K. Risk of Invasive Cutaneous Squamous Cell Carcinoma After Different Treatments for Actinic Keratosis: A Secondary Analysis of a Randomized Clinical Trial. JAMA Dermatol. 2022 Jun 1;158(6):634-640. doi: 10.1001/jamadermatol.2022.1034.
citation: Ahmady S, Jansen MHE, Nelemans PJ, Essers BAB, Kessels JPHM, Kelleners-Smeets NWJ, Mosterd K. The Effect of Four Approaches to Treat Actinic Keratosis on the Health-Related QOL, as Assessed by the Skindex-29 and Actinic Keratosis QOL. J Invest Dermatol. 2021 Jul;141(7):1830-1832. doi: 10.1016/j.jid.2020.12.023. Epub 2021 Jan 18. No abstract available.
citation: Jansen MHE, Kessels JPHM, Merks I, Nelemans PJ, Kelleners-Smeets NWJ, Mosterd K, Essers BAB. A trial-based cost-effectiveness analysis of topical 5-fluorouracil vs. imiquimod vs. ingenol mebutate vs. methyl aminolaevulinate conventional photodynamic therapy for the treatment of actinic keratosis in the head and neck area performed in the Netherlands. Br J Dermatol. 2020 Oct;183(4):738-744. doi: 10.1111/bjd.18884. Epub 2020 Feb 19.
citation: Jansen MHE, Kessels JPHM, Nelemans PJ, Kouloubis N, Arits AHMM, van Pelt HPA, Quaedvlieg PJF, Essers BAB, Steijlen PM, Kelleners-Smeets NWJ, Mosterd K. Randomized Trial of Four Treatment Approaches for Actinic Keratosis. N Engl J Med. 2019 Mar 7;380(10):935-946. doi: 10.1056/NEJMoa1811850.