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

NCT03909646 | Completed Phase 4

• 1 other identifier: 67545
• Study Type: interventional
• Target: 250
• Locations: 1 country
• Sites: 1

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, 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.

Conditions

Bowen's Disease

Outcome Measures

Primary Outcomes (1)

• Sustained clearance (no residue, recurrence nor progression)

  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 Outcomes (1)

• 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.

  3 months and at least 3 years post-treatment

Study Arms (3)

Surgical excision

ACTIVE COMPARATOR

Standard surgical excision with 5 mm safety margin

Other: Surgical excision

Photodynamic therapy

ACTIVE COMPARATOR

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

5% 5-Fluorouracil

ACTIVE COMPARATOR

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

Drug: 5Fluorouracil

Interventions

Methyl Aminolevulinate (Mal) for Topical Administration, 16.8%, 1 Gram DRUG

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.

Also known as: Metvix

Photodynamic therapy

5Fluorouracil DRUG

5-FU is applied on the treatment area by the patient in a thin layer twice daily during 4 weeks.

Also known as: Efudix

5% 5-Fluorouracil

Surgical excision OTHER

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

Surgical excision

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Maastricht University Medical Center: lead

Study Sites (1)

MUMC+

Maastricht, Limburg, Netherlands

Location

Related Publications (21)

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MeSH Terms

Conditions

Bowen's Disease

Interventions

methyl 5-aminolevulinate; Myelin and Lymphocyte-Associated Proteolipid Proteins; Fluorouracil

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell

Intervention Hierarchy (Ancestors)

Proteolipids; Membrane Lipids; Lipids; MARVEL Domain-Containing Proteins; Membrane Proteins; Proteins; Amino Acids, Peptides, and Proteins; Myelin Proteins; Vesicular Transport Proteins; Nerve Tissue Proteins; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Klara Mosterd, Professor

  Maastricht University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: April 8, 2019
• First Posted: April 10, 2019
• Study Start: May 27, 2019
• Primary Completion: March 2, 2022
• Study Completion: December 12, 2024
• Last Updated: May 6, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)