IM Versus 5-FU Versus IMI Versus MAL-PDT in Treatment of Actinic Keratosis (Akti)

Maastricht University Medical Centre (MUMC)

Status and phase: Unknown; Phase 4

Conditions: Keratosis, Actinic

Treatments: Drug: 5-fluorouracil; Procedure: methylaminolevulinate photodynamic therapy; Drug: Ingenol mebutate; Drug: Imiquimod

Study type: Interventional

Funder types: Other

Identifiers

NCT02281682

2014-003691-23 (EudraCT Number)

NL50621.068.14

836031011 (Other Grant/Funding Number)

Details and patient eligibility

About

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.

Full 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).

Enrollment: 624 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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624 participants in 4 patient groups

Imiquimod

Active Comparator group

Description:

three times a week once daily during 4 consecutive weeks. Prior to treatment: curettage

Treatment:

Drug: Ingenol mebutate

Procedure: methylaminolevulinate photodynamic therapy

Drug: 5-fluorouracil

5-Fluorouracil

Active Comparator group

Description:

during 4 (consecutive) weeks twice daily. Prior to treatment: curettage

Treatment:

Drug: Ingenol mebutate

Drug: Imiquimod

Procedure: methylaminolevulinate photodynamic therapy

Ingenol mebutate 0.015%

Active Comparator group

Description:

during 3 (consecutive) days once daily. Prior to treatment: curettage

Treatment:

Drug: Imiquimod

Procedure: methylaminolevulinate photodynamic therapy

Drug: 5-fluorouracil

MAL-PDT

Active Comparator group

Description:

methylaminolevulinate photodynamic therapy; one session. Prior to treatment: curettage

Treatment:

Drug: Ingenol mebutate

Drug: Imiquimod

Drug: 5-fluorouracil