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BOWTIE: Surgical Excision Versus Photodynamic Therapy and Topical 5-fluorouracil in Treatment of Bowen's Disease

Sponsor
Maastricht University Medical Center (Other)
Overall Status
Recruiting
CT.gov ID
NCT03909646
Collaborator
(none)
250
Enrollment
1
Location
3
Arms
78.2
Anticipated Duration (Months)
3.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

There is limited quality research on the effectiveness of treatments in Bowen's disease (BD). Patient and lesion characteristics, patient preferences and costs should be considered when choosing therapy. Surgical excision (SE), photodynamic therapy (PDT) and 5-fluorouracil (5FU) are mentioned as treatment options in guidelines. However no clear and evidence based recommendations are made in terms of effectiveness.

Objective: The aim of this study is 1) to evaluate the (cost)effectiveness of 5FU and PDT compared to SE in BD and 2) to compare the effectiveness of 5FU with that of PDT. With a better understanding of the (cost)effectiveness of alternative treatment options, the investigators will supply the necessary evidence for national and international guidelines, to achieve more uniformity in treatment of BD.

Study design: Randomized controlled non-inferiority multicenter trial. Study population:

Patients ≥18 years, with a histological proven primary lesion of Bowen's disease, visiting Maastricht University Medical Centre, Catharina hospital Eindhoven, VieCuri MC Venlo or Zuyderland Medical Centre Heerlen.

Intervention: One group undergoes SE with a 5mm safety margin followed by routine histological examination. The other group receives PDT with application of methyl aminolevulinate (MAL) cream followed by two illuminations with a one-week interval. The third group receives 5FU cream, which has to be applied by the patient twice daily for 4 weeks.

Main study parameters/endpoints: The primary outcome is the proportion of patients with sustained clearance at 12 months post-treatment. Secondary outcomes are proportion of patients with clearance at 3 months, 3-year and 5-year probability of sustained clearance, cost-effectiveness, patient satisfaction, patient preferences, compliance, side effects and cosmetic outcome. Post-treatment, patients will be asked to answer a short questionnaire regarding side effects, experience with the treatment and satisfaction.

Condition or Disease Intervention/Treatment Phase
  • Drug: Methyl Aminolevulinate (Mal) for Topical Administration, 16.8%, 1 Gram
  • Drug: 5Fluorouracil
  • Other: Surgical excision
 Phase 4

Detailed Description

This is a multicenter randomized controlled non-inferiority trial, conducted in one academic and three non-academic hospitals. A multicenter approach (academic and non-academic centers) increases the generalizability of the study results. The study takes place at the dermatology department of Maastricht University Medical Centre (MUMC+), Catharina hospital Eindhoven, VieCuri Medical Centre Venlo and Zuyderland Medical Centre Heerlen.

A non-inferiority design was chosen because although the noninvasive treatments are expected to be somewhat less effective in terms of remaining free of recurrence, there are other benefits such as higher patient satisfaction, patient preferences and better cosmetic outcome. It should be noted that BD is a noninvasive disease and recurrences can be treated with surgical excision without compromising the patient's health.

After giving permission and signing the informed consent form, eligible patients will be randomly assigned to one of three treatment groups: 1) PDT, 2) 5% 5FU cream, 3) surgical excision. All interventions are part of regular care. For the treatment of BD 5% 5FU cream (Efudix®) has been approved by the European Medicines Agency (EMA).

The coordinating investigator who is not blinded to the randomized treatment will prescribe the 5FU cream or give orders to plan PDT or excision and provide patients with further information. The supervising dermatologist will be blinded to treatment allocation, and will be asked to assess outcome measures such as clearance and cosmetic evaluation. Relevant baseline characteristics will be registered (e.g. prior history of skin cancer, age, gender, use of immunosuppressant medication in history, prior treatments for non-melanoma skin cancer), dermatological description of the lesion, size and localization of the lesion and the histological tumour thickness. The presence of other lesions, besides the target lesion, and their treatment will be recorded

The primary outcome will be the proportion of patients with sustained clearance at 12 months follow-up after the end of treatment. Secondary outcomes will be the proportion of patients with clearance at 3 months, 3-year and 5-year probability of sustained clearance, cost-effectiveness, patient satisfaction, compliance, side effects and cosmetic outcome.

Residual tumour at 3 months follow-up and recurrent tumour at 12 months follow-up is considered as treatment failure and will be treated with surgery.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
250 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Single (Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Surgical Excision Versus Photodynamic Therapy and Topical 5-fluorouracil in Treatment of Bowen's Disease: a Multicenter Randomized Controlled Trial
Actual Study Start Date :
May 27, 2019
Anticipated Primary Completion Date :
Dec 1, 2021
Anticipated Study Completion Date :
Dec 1, 2025

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Surgical excision

Standard surgical excision with 5 mm safety margin

Other: Surgical excision
Local anesthesia with lidocain 1% (1-2ml) will be used before performing standard surgical excision with 5 mm safety margin followed by routine histological examination. The skin will be closed using cutaneous sutures, which will be removed after 1-2 weeks. The surgical excision will take place in the hospital by the treating physician
Active Comparator: Photodynamic therapy

PDT with application of methyl aminolevulinate (MAL) cream followed by two illuminations with a one-week interval

Drug: Methyl Aminolevulinate (Mal) for Topical Administration, 16.8%, 1 Gram
A layer of methylaminolevulinc acid 160 mg/g cream (about 1 mm thick) is applied to the lesion, with a clinical margin of 5-10 mm surrounding of normal skin and then covered by an occlusive dressing. After 3 hours the occlusive dressing will be removed and the area is illuminated with Omnilux or Actilite (Galderma). After PDT the treatment site is covered again with the above mentioned occlusive dressings during 48 hours. Treatment is performed by an authorized nurse in the hospital. Two sessions should be administered with an interval of one week between sessions.
Other Names:
  • Metvix

    		•
    Active Comparator: 5% 5-Fluorouracil

    5FU cream, which has to be applied by the patient twice daily for 4 weeks.

    Drug: 5Fluorouracil
    5-FU is applied on the treatment area by the patient in a thin layer twice daily during 4 weeks.
    Other Names:
  • Efudix

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Sustained clearance (no residue, recurrence nor progression) [12 months post-treatment]

      The main study endpoint is the proportion of patients with sustained clearance (no residue, recurrence nor progression) 12 months post-treatment.

    Secondary Outcome Measures

    1. the proportion of patients with clearance at 3 months post-treatment, 3-year and 5-year probability of sustained clearance, cost-effectiveness, patient satisfaction, patient preferences, compliance, side effects and cosmetic outcome. [3 months, 3-years and 5- years post-treatment]

      the proportion of patients with clearance at 3 months post-treatment, 3-year and 5-year probability of sustained clearance, cost-effectiveness, patient satisfaction, patient preferences, compliance, side effects and cosmetic outcome.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Adults ≥ 18 years

    • Histologically proven primary Bowen's disease

    • Lesions ≥ 4mm and ≤ 40mm in diameter

    • Fitzpatrick skin type I-IV

    • Female in child bearing potential should be using contraceptive measures, during and till 3 months post-treatment

    Exclusion Criteria:

    • Bowen's Disease located at ears, periocular, nail unit or periungual tissue, nose, genital and mucous membranes

    • High clinical suspicion of invasive SCC

    • Interfering treatment of other (N)MSC in target area

    • Not able to self-apply cream on lesions located on the back or other difficult to reach locations

    • Pregnancy

    • Breastfeeding

    • Allergy to study drugs

    • Genetic skin cancer disorders

    • Not understanding Dutch language

    • Porphyria

    • Not able to give informed consent

    • 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, in-terferon, opioids, TNF binding proteins, MMF, biologic agents). Inhalation corticoster-oids / nasal corticosteroids are permitted.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 MUMC+ Maastricht Limburg Netherlands

    Sponsors and Collaborators

    • Maastricht University Medical Center

    Investigators

    • Principal Investigator: Klara Mosterd, UHD, Dernatologist at Maastricht University Medical Center

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Maastricht University Medical Center
    ClinicalTrials.gov Identifier:
    NCT03909646
    Other Study ID Numbers:
    • 67545
    First Posted:
    Apr 10, 2019
    Last Update Posted:
    Oct 27, 2020
    Last Verified:
    Oct 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Bowen's Disease
    Fluorouracil
    Aminolevulinic Acid
    Methyl 5-aminolevulinate

    Study Results

    No Results Posted as of Oct 27, 2020