- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02281682
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
Unknown
Conditions
Intervention / Treatment
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:
during 3 (consecutive) days once daily.
Prior to treatment: curettage
Other Names:
methylaminolevulinate photodynamic therapy; one session.
Prior to treatment: curettage
Other Names:
|
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:
methylaminolevulinate photodynamic therapy; one session.
Prior to treatment: curettage
Other Names:
three times a week once daily during 4 consecutive weeks.
Prior to treatment: curettage
Other Names:
|
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:
methylaminolevulinate photodynamic therapy; one session.
Prior to treatment: curettage
Other Names:
three times a week once daily during 4 consecutive weeks.
Prior to treatment: curettage
Other Names:
|
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:
during 3 (consecutive) days once daily.
Prior to treatment: curettage
Other Names:
three times a week once daily during 4 consecutive weeks.
Prior to treatment: curettage
Other Names:
|
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.
General Publications
- 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.
- 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.
- 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.
- 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.
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
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Skin Diseases
- Neoplasms
- Precancerous Conditions
- Keratosis, Actinic
- Keratosis
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Photosensitizing Agents
- Dermatologic Agents
- Adjuvants, Immunologic
- Interferon Inducers
- Fluorouracil
- Imiquimod
- Methyl 5-aminolevulinate
Other Study ID 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.
Clinical Trials on Keratosis, Actinic
-
Dolorgiet GmbH & Co. KGd.s.h. statistical services GmbH; CenTrial GmbHCompletedActinic Keratosis Olsen Grade I/IIGermany
-
Cosmetique Active InternationalNot yet recruiting
-
Centre Dermatologique du RoyCompleted
-
Encube Ethicals Pvt. Ltd.CBCC Global ResearchCompleted
-
University of California, DavisActive, not recruiting
-
Northwestern UniversityWithdrawn
-
Tulane UniversityMayne Pharma International Pty LtdTerminatedActinic KeratosesUnited States
-
Medical University of ViennaTerminatedActinic KeratosesAustria
-
University Hospital RegensburgGerman Research FoundationCompleted
-
St Vincent's University Hospital, IrelandCompleted
Clinical Trials on 5-fluorouracil
-
The Netherlands Cancer InstituteCompleted
-
The Netherlands Cancer InstituteCompleted
-
The Cleveland ClinicNational Cancer Institute (NCI)TerminatedActinic Keratosis | Organ or Tissue Transplant; ComplicationsUnited States
-
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.UnknownSquamous Cell Carcinoma of the Head and NeckChina
-
National Cancer Institute (NCI)CompletedStage IV Colon Cancer | Stage IV Rectal Cancer | Recurrent Colon Cancer | Recurrent Rectal Cancer | Adenocarcinoma of the Rectum | Adenocarcinoma of the ColonUnited States
-
Wake Forest University Health SciencesNational Cancer Institute (NCI)TerminatedMucinous Adenocarcinoma of the Rectum | Stage IIA Rectal Cancer | Stage IIB Rectal Cancer | Stage IIC Rectal Cancer | Stage IIIB Rectal Cancer | Stage IIIC Rectal CancerUnited States
-
Peking Union Medical College HospitalRecruitingRectal Cancer | Colon Cancer | Chemotherapy Effect | PTC | Exon MutationChina
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)CompletedColorectal Cancer | Metastatic CancerUnited States
-
Singapore National Eye CentreSingapore Eye Research Institute; Nanchang UniversityCompletedGlaucoma | Wound Healing | TrabeculectomySingapore