NCT02281682

Brief 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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
624

participants targeted

Target at P75+ for phase_4

Timeline
Completed

Started Nov 2014

Longer than P75 for phase_4

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 28, 2014

Completed
4 days until next milestone

Study Start

First participant enrolled

November 1, 2014

Completed
2 days until next milestone

First Posted

Study publicly available on registry

November 3, 2014

Completed
3.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2018

Completed
5 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2018

Completed
Last Updated

October 30, 2017

Status Verified

October 1, 2017

Enrollment Period

3.7 years

First QC Date

October 28, 2014

Last Update Submit

October 27, 2017

Conditions

Keratosis, Actinic

Keywords

Keratosis, ActinicTreatment Outcomecost-effectivenesseconomic evaluationimiquimodphotodynamic therapytopical fluorouracilingenol mebutate

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (12)

  • treatment failure

    12 months

  • Treatment succes at 3 months post treatment

    3 months

  • complete lesion clearance

    12 months

  • SCC

    12 months

  • side effects

    12 months

  • +7 more secondary outcomes

Study Arms (4)

Imiquimod

ACTIVE COMPARATOR

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

Drug: 5-fluorouracilDrug: Ingenol mebutateProcedure: methylaminolevulinate photodynamic therapy

5-Fluorouracil

ACTIVE COMPARATOR

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

Drug: ImiquimodDrug: Ingenol mebutateProcedure: methylaminolevulinate photodynamic therapy

Ingenol mebutate 0.015%

ACTIVE COMPARATOR

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

Drug: ImiquimodDrug: 5-fluorouracilProcedure: methylaminolevulinate photodynamic therapy

MAL-PDT

ACTIVE COMPARATOR

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

Drug: ImiquimodDrug: 5-fluorouracilDrug: Ingenol mebutate

Interventions

ImiquimodDRUG

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

Also known as: Aldara
5-FluorouracilIngenol mebutate 0.015%MAL-PDT
5-fluorouracilDRUG

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

Also known as: Efudix
ImiquimodIngenol mebutate 0.015%MAL-PDT
Ingenol mebutateDRUG

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

Also known as: Picato
5-FluorouracilImiquimodMAL-PDT
methylaminolevulinate photodynamic therapyPROCEDURE

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

Also known as: MAL-PDT
5-FluorouracilImiquimodIngenol mebutate 0.015%

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Maastricht UMC

Maastricht, Limburg, 6202 AZ, Netherlands

Location

Related Publications (4)

  • 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.

    PMID: 35475852DERIVED

  • 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.

    PMID: 33476658DERIVED

  • 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.

    PMID: 31961446DERIVED

  • 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.

    PMID: 30855743DERIVED

MeSH Terms

Conditions

Keratosis, Actinic

Interventions

ImiquimodFluorouracil3-ingenyl angelate

Condition Hierarchy (Ancestors)

Precancerous ConditionsNeoplasmsKeratosisSkin DiseasesSkin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

AminoquinolinesQuinolinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsUracilPyrimidinonesPyrimidinesHeterocyclic Compounds, 1-Ring

Study Officials

  • Klara Mosterd, MD, PhD

    Maastricht University Hospital

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 28, 2014

First Posted

November 3, 2014

Study Start

November 1, 2014

Primary Completion

July 1, 2018

Study Completion

December 1, 2018

Last Updated

October 30, 2017

Record last verified: 2017-10

Locations

NL(1)