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

May 2, 2025 updated by: Maastricht University Medical Center

Surgical Excision Versus Photodynamic Therapy and Topical 5-fluorouracil in Treatment of Bowen's Disease: a Multicenter Randomized Controlled Trial

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, the long-term 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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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, the long-term 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 Type

Interventional

Enrollment (Actual)

250

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

  • Netherlands
    • Limburg
      • Maastricht, Limburg, Netherlands
        • MUMC+

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

Description

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.

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: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Sustained clearance (no residue, recurrence nor progression)
Time Frame: 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.
12 months post-treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
the proportion of patients with clearance at 3 months post-treatment, the long-term probability of sustained clearance, cost-effectiveness, patient satisfaction, patient preferences, compliance, side effects and cosmetic outcome.
Time Frame: 3 months and at least 3 years post-treatment

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

Long-term is defined as at least 3 years post-treatment. All patients will be invited for the long-term follow-up visit at least 3 years after finishing treatment, with the last patient finishing treatment at April 16th 2021.
3 months and at least 3 years post-treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Maastricht University Medical Center

Investigators

  • Principal Investigator: Klara Mosterd, Professor, Maastricht University Medical Center

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

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 (Actual)

May 27, 2019

Primary Completion (Actual)

March 2, 2022

Study Completion (Actual)

December 12, 2024

Study Registration Dates

First Submitted

April 8, 2019

First Submitted That Met QC Criteria

April 9, 2019

First Posted (Actual)

April 10, 2019

Study Record Updates

Last Update Posted (Actual)

May 6, 2025

Last Update Submitted That Met QC Criteria

May 2, 2025

Last Verified

May 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 67545

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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.

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