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

October 27, 2017 updated by: Maastricht University Medical Center

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

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.

Study Overview

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).

Study Type

Interventional

Enrollment (Actual)

624

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Limburg
      • Maastricht, Limburg, Netherlands, 6202 AZ
        • Maastricht UMC

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Imiquimod
three times a week once daily during 4 consecutive weeks. Prior to treatment: curettage
during 4 (consecutive) weeks twice daily. Prior to treatment: curettage
Other Names:
  • Efudix
during 3 (consecutive) days once daily. Prior to treatment: curettage
Other Names:
  • Picato
methylaminolevulinate photodynamic therapy; one session. Prior to treatment: curettage
Other Names:
  • MAL-PDT
Active Comparator: 5-Fluorouracil
during 4 (consecutive) weeks twice daily. Prior to treatment: curettage
during 3 (consecutive) days once daily. Prior to treatment: curettage
Other Names:
  • Picato
methylaminolevulinate photodynamic therapy; one session. Prior to treatment: curettage
Other Names:
  • MAL-PDT
three times a week once daily during 4 consecutive weeks. Prior to treatment: curettage
Other Names:
  • Aldara
Active Comparator: Ingenol mebutate 0.015%
during 3 (consecutive) days once daily. Prior to treatment: curettage
during 4 (consecutive) weeks twice daily. Prior to treatment: curettage
Other Names:
  • Efudix
methylaminolevulinate photodynamic therapy; one session. Prior to treatment: curettage
Other Names:
  • MAL-PDT
three times a week once daily during 4 consecutive weeks. Prior to treatment: curettage
Other Names:
  • Aldara
Active Comparator: MAL-PDT
methylaminolevulinate photodynamic therapy; one session. Prior to treatment: curettage
during 4 (consecutive) weeks twice daily. Prior to treatment: curettage
Other Names:
  • Efudix
during 3 (consecutive) days once daily. Prior to treatment: curettage
Other Names:
  • Picato
three times a week once daily during 4 consecutive weeks. Prior to treatment: curettage
Other Names:
  • Aldara

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
treatment succes
Time Frame: 12 months
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
treatment failure
Time Frame: 12 months
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
Treatment succes at 3 months post treatment
Time Frame: 3 months
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
complete lesion clearance
Time Frame: 12 months
proportion of lesions with 100% clearance in all treated patients at 3 and 12 months post final treatment.
12 months
SCC
Time Frame: 12 months
Proportion of patients who develop a SCC in the treatment area during study follow-up.
12 months
side effects
Time Frame: 12 months
local skin reactions reported in patient diary, visual analogue score (VAS), Patient-reported adverse events
12 months
Cosmetic outcome
Time Frame: 3 and 12 months
based on a Cosmetic questionnaire, filled in on baseline, 3 + 12 months
3 and 12 months
patient satisfaction
Time Frame: 12 months
Skindex-29 questionnaire (quality of life) , Actinic Keratosis Quality of Life (AKQoL) questionnaire; filled in on baseline, 3 + 12 months
12 months
treatment compliance
Time Frame: 3 months
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
Overall decrease in AK
Time Frame: 3 and 12 months
Decrease in number AK from baseline per patient, at 3 and 12 months post final treatment.
3 and 12 months
Cost-effectiveness
Time Frame: 12 months
Healthcare/treatment costs
12 months
Investigator Global Improvement Indices
Time Frame: 3 and 12 months
Investigator Global Improvement Indices (IGII) at 3 and 12 months post final treatment.
3 and 12 months
Number of new lesions
Time Frame: 3 and 12 months
Number of new lesions at 3 and 12 months post final treatment
3 and 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Klara Mosterd, MD, PhD, Maastricht University Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2014

Primary Completion (Anticipated)

July 1, 2018

Study Completion (Anticipated)

December 1, 2018

Study Registration Dates

First Submitted

October 28, 2014

First Submitted That Met QC Criteria

October 30, 2014

First Posted (Estimate)

November 2, 2014

Study Record Updates

Last Update Posted (Actual)

October 30, 2017

Last Update Submitted That Met QC Criteria

October 27, 2017

Last Verified

October 1, 2017

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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