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

Keratosis, Actinic Clinical Trial

— Akti  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02281682
• Other study ID #: NL50621.068.14
• Secondary ID: 8360310112014-00
• Status: Active, not recruiting
• Phase: Phase 4
• First received: October 28, 2014
• Last updated: October 27, 2017
• Start date: November 2014
• Est. completion date: December 2018

Study information

• Verified date: October 2017
• Source: Maastricht University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 624
• Est. completion date: December 2018
• Est. primary completion date: July 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Keratosis
• Keratosis, Actinic

Intervention

Drug:
• Imiquimod
three times a week once daily during 4 consecutive weeks. Prior to treatment: curettage
• 5-fluorouracil
during 4 (consecutive) weeks twice daily. Prior to treatment: curettage
• Ingenol mebutate
during 3 (consecutive) days once daily. Prior to treatment: curettage

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

Locations

Country	Name	City	State
Netherlands	Maastricht UMC	Maastricht	Limburg

Sponsors (1)

Lead Sponsor	Collaborator
Maastricht University Medical Center

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	treatment succes	the proportion of patients with =75% lesion reduction in the number of AK lesions counted at baseline in the treatment area 12 months post final treatment (= 75% patient clearance at 12 months).	12 months
Secondary	treatment failure	proportion of participants with <75% reduction in number of AK lesions after 3 and 12 months post final treatment compared to baseline (<75% patient clearance at 3 and 12 months).	12 months
Secondary	Treatment succes at 3 months post treatment	proportion of participants with =75% reduction in number of AK lesions at 3 months post final treatment (= 75% patient clearance at 3 months).	3 months
Secondary	complete lesion clearance	proportion of lesions with 100% clearance in all treated patients at 3 and 12 months post final treatment.	12 months
Secondary	SCC	Proportion of patients who develop a SCC in the treatment area during study follow-up.	12 months
Secondary	side effects	local skin reactions reported in patient diary, visual analogue score (VAS), Patient-reported adverse events	12 months
Secondary	Cosmetic outcome	based on a Cosmetic questionnaire, filled in on baseline, 3 + 12 months	3 and 12 months
Secondary	patient satisfaction	Skindex-29 questionnaire (quality of life) , Actinic Keratosis Quality of Life (AKQoL) questionnaire; filled in on baseline, 3 + 12 months	12 months
Secondary	treatment compliance	defined as the number of applied treatments as percentage of the number of prescribed treatments, based on patient diaries and weighing returned medication.	3 months
Secondary	Overall decrease in AK	Decrease in number AK from baseline per patient, at 3 and 12 months post final treatment.	3 and 12 months
Secondary	Cost-effectiveness	Healthcare/treatment costs	12 months
Secondary	Investigator Global Improvement Indices	Investigator Global Improvement Indices (IGII) at 3 and 12 months post final treatment.	3 and 12 months
Secondary	Number of new lesions	Number of new lesions at 3 and 12 months post final treatment	3 and 12 months