Surgical Excision Versus Photodynamic Therapy and Topical 5-fluorouracil in Treatment of Bowen's Disease: a Multicenter Randomized Controlled Trial
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 250
- 试验地点
- 1
- 主要终点
- Sustained clearance (no residue, recurrence nor progression)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
Surgical excision
Standard surgical excision with 5 mm safety margin
干预措施: Surgical excision (Other)
Photodynamic therapy
PDT with application of methyl aminolevulinate (MAL) cream followed by two illuminations with a one-week interval
干预措施: Methyl Aminolevulinate (Mal) for Topical Administration, 16.8%, 1 Gram (Drug)
5% 5-Fluorouracil
5FU cream, which has to be applied by the patient twice daily for 4 weeks.
干预措施: 5Fluorouracil (Drug)
结局指标
主要结局
Sustained clearance (no residue, recurrence nor progression)
时间窗: 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.
次要结局
- 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)