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

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
624

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

  • Netherlands
    • 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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Imiquimod
three times a week once daily during 4 consecutive weeks. Prior to treatment: curettage
Drug: 5-fluorouracil
during 4 (consecutive) weeks twice daily. Prior to treatment: curettage
Other Names:
  • Efudix
Drug: Ingenol mebutate
during 3 (consecutive) days once daily. Prior to treatment: curettage
Other Names:
  • Picato
Procedure: methylaminolevulinate photodynamic therapy
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
Drug: Ingenol mebutate
during 3 (consecutive) days once daily. Prior to treatment: curettage
Other Names:
  • Picato
Procedure: methylaminolevulinate photodynamic therapy
methylaminolevulinate photodynamic therapy; one session. Prior to treatment: curettage
Other Names:
  • MAL-PDT
Drug: Imiquimod
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
Drug: 5-fluorouracil
during 4 (consecutive) weeks twice daily. Prior to treatment: curettage
Other Names:
  • Efudix
Procedure: methylaminolevulinate photodynamic therapy
methylaminolevulinate photodynamic therapy; one session. Prior to treatment: curettage
Other Names:
  • MAL-PDT
Drug: Imiquimod
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
Drug: 5-fluorouracil
during 4 (consecutive) weeks twice daily. Prior to treatment: curettage
Other Names:
  • Efudix
Drug: Ingenol mebutate
during 3 (consecutive) days once daily. Prior to treatment: curettage
Other Names:
  • Picato
Drug: Imiquimod
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Maastricht University Medical Center

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • 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.

General Publications

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

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 1, 2014

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 1, 2018

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 28, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 30, 2014

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 2, 2014

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 30, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 27, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • NL50621.068.14
  • 836031011 (Other Grant/Funding Number: ZonMw)
  • 2014-003691-23 (EudraCT Number)

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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