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

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ClinicalTrials.gov Identifier: NCT02281682
Recruitment Status : Unknown
Verified October 2017 by Maastricht University Medical Center.
Recruitment status was:  Active, not recruiting
First Posted : November 2, 2014
Last Update Posted : October 30, 2017
Sponsor:
Information provided by (Responsible Party):
Maastricht University Medical Center

Study Description
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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.

Condition or disease Intervention/treatment Phase
Keratosis, Actinic Drug: Imiquimod Drug: 5-fluorouracil Drug: Ingenol mebutate Procedure: methylaminolevulinate photodynamic therapy Phase 4

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 Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 624 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Investigator)
Primary Purpose: Treatment
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
Study Start Date : November 2014
Estimated Primary Completion Date : July 2018
Estimated Study Completion Date : December 2018

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
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 Name: Efudix

Drug: Ingenol mebutate
during 3 (consecutive) days once daily. Prior to treatment: curettage
Other Name: Picato

Procedure: methylaminolevulinate photodynamic therapy
methylaminolevulinate photodynamic therapy; one session. Prior to treatment: curettage
Other Name: MAL-PDT
Active Comparator: 5-Fluorouracil
during 4 (consecutive) weeks twice daily. Prior to treatment: curettage
 Drug: Imiquimod
three times a week once daily during 4 consecutive weeks. Prior to treatment: curettage
Other Name: Aldara

Drug: Ingenol mebutate
during 3 (consecutive) days once daily. Prior to treatment: curettage
Other Name: Picato

Procedure: methylaminolevulinate photodynamic therapy
methylaminolevulinate photodynamic therapy; one session. Prior to treatment: curettage
Other Name: MAL-PDT
Active Comparator: Ingenol mebutate 0.015%
during 3 (consecutive) days once daily. Prior to treatment: curettage
 Drug: Imiquimod
three times a week once daily during 4 consecutive weeks. Prior to treatment: curettage
Other Name: Aldara

Drug: 5-fluorouracil
during 4 (consecutive) weeks twice daily. Prior to treatment: curettage
Other Name: Efudix

Procedure: methylaminolevulinate photodynamic therapy
methylaminolevulinate photodynamic therapy; one session. Prior to treatment: curettage
Other Name: MAL-PDT
Active Comparator: MAL-PDT
methylaminolevulinate photodynamic therapy; one session. Prior to treatment: curettage
 Drug: Imiquimod
three times a week once daily during 4 consecutive weeks. Prior to treatment: curettage
Other Name: Aldara

Drug: 5-fluorouracil
during 4 (consecutive) weeks twice daily. Prior to treatment: curettage
Other Name: Efudix

Drug: Ingenol mebutate
during 3 (consecutive) days once daily. Prior to treatment: curettage
Other Name: Picato


Outcome Measures
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Primary Outcome Measures :
  1. 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).


Secondary Outcome Measures :
  1. 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).

  2. 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. 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.

  4. SCC [ Time Frame: 12 months ]
    Proportion of patients who develop a SCC in the treatment area during study follow-up.

  5. side effects [ Time Frame: 12 months ]
    local skin reactions reported in patient diary, visual analogue score (VAS), Patient-reported adverse events

  6. Cosmetic outcome [ Time Frame: 3 and 12 months ]
    based on a Cosmetic questionnaire, filled in on baseline, 3 + 12 months

  7. 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

  8. 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.

  9. 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.

  10. Cost-effectiveness [ Time Frame: 12 months ]
    Healthcare/treatment costs

  11. Investigator Global Improvement Indices [ Time Frame: 3 and 12 months ]
    Investigator Global Improvement Indices (IGII) at 3 and 12 months post final treatment.

  12. Number of new lesions [ Time Frame: 3 and 12 months ]
    Number of new lesions at 3 and 12 months post final treatment


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02281682


Locations
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Netherlands
Maastricht UMC
Maastricht, Limburg, Netherlands, 6202 AZ
Sponsors and Collaborators
Maastricht University Medical Center
Investigators
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Principal Investigator: Klara Mosterd, MD, PhD Maastricht University Hospital
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Maastricht University Medical Center
ClinicalTrials.gov Identifier: NCT02281682    
Other Study ID Numbers: NL50621.068.14
836031011 ( Other Grant/Funding Number: ZonMw )
2014-003691-23 ( EudraCT Number )
First Posted: November 2, 2014    Key Record Dates
Last Update Posted: October 30, 2017
Last Verified: October 2017
Keywords provided by Maastricht University Medical Center:
Keratosis, Actinic
Treatment Outcome
cost-effectiveness
economic evaluation
 imiquimod
photodynamic therapy
topical fluorouracil
ingenol mebutate
Additional relevant MeSH terms:
Layout table for MeSH terms
Keratosis, Actinic
Keratosis
Skin Diseases
Precancerous Conditions
Neoplasms
Fluorouracil
Imiquimod
Methyl 5-aminolevulinate
Aminolevulinic Acid
Antimetabolites
 Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Adjuvants, Immunologic
Interferon Inducers
Photosensitizing Agents
Dermatologic Agents