Clinical Trial: IM Versus 5-FU Versus IMI Versus MAL-PDT in Treatment of Actinic Keratosis

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

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

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.

Detailed Summary: 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).
Sponsor: Maastricht University Medical Center

Current Primary Outcome: 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).


Original Primary Outcome: treatment succes [ Time Frame: 12 months ]

Treatment success at 12 months post treatment, defined as the proportion of patients with ≥75% lesion reduction from baseline in the number of AK lesions in the treatment area. This will be assessed by counting the total number of AK lesions (total lesion number score, TLNS).


Current Secondary Outcome:

  • 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).
  • 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).
  • 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.
  • SCC [ Time Frame: 12 months ]
    Proportion of patients who develop a SCC in the treatment area during study follow-up.
  • side effects [ Time Frame: 12 months ]
    local skin reactions reported in patient diary, visual analogue score (VAS), Patient-reported adverse events
  • Cosmetic outcome [ Time Frame: 3 and 12 months ]
    based on a Cosmetic questionnaire, filled in on baseline, 3 + 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
  • 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.
  • 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.
  • Cost-effectiveness [ Time Frame: 12 months ]
    Healthcare/treatment costs
  • Investigator Global Improvement Indices [ Time Frame: 3 and 12 months ]
    Investigator Global Improvement Indices (IGII) at 3 and 12 months post final treatment.
  • Number of new lesions [ Time Frame: 3 and 12 months ]
    Number of new lesions at 3 and 12 months post final treatment


Original Secondary Outcome:

  • partial response [ Time Frame: 12 months ]
    proportion of participants with 50-75% reduction in number of AK lesions
  • treatment failure [ Time Frame: 12 months ]
    proportion of participants with <50% reduction in number of AK lesions
  • partial lesion clearance [ Time Frame: 12 months ]
    proportion of lesions with ≥75% clearance
  • complete lesion clearance [ Time Frame: 12 months ]
    proportion of lesions with 100% clearance
  • SCC [ Time Frame: 12 months ]
    proportion of patients who develop SCC in treated areas
  • side effects [ Time Frame: 12 months ]
    local skin reactions reported in patient diary, visual analogue score (VAS), Patient-reported adverse events
  • Cosmetic outcome [ Time Frame: 12 months ]
    based on a Cosmetic questionnaire, filled in on baseline, 3 + 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
  • treatment compliance [ Time Frame: 3 months ]
    based on a patient diary
  • Overall decrease in AK [ Time Frame: 12 months ]
    decrease in number AK from baseline per patient
  • Cost-effectiveness [ Time Frame: 12 months ]
    Cost-effectiveness
  • Non-responders [ Time Frame: 15 months ]
    proportion of participants with repeated treatment because of treatment failure after first treatment session, with <50% reduction in number of AK lesions at 12 months post second treatment
  • Treatment success after repeated treatment [ Time Frame: 15 months ]
    proportion of participants who received second treatment because of treatment failure with 50-75% reduction in number of AK lesions at 12 months post second treatment


Information By: Maastricht University Medical Center

Dates:
Date Received: October 28, 2014
Date Started: January 2015
Date Completion: January 2018
Last Updated: September 22, 2015
Last Verified: September 2015