Surgical Excision Versus Combined Treatment With Curettage and Imiquimod for Nodular Basal Cell Carcinoma: an Open, Non-inferiority, Randomized Controlled Trial
试验速览
- 阶段
- 3 期
- 入组人数
- 145
- 试验地点
- 1
- 主要终点
- Proportion of participants tumour-free
研究概览
简要总结
Basal cell carcinoma (BCC) is a slow-growing, locally invasive malignant epidermal skin tumour. It is the most common malignant disease in Caucasians, representing approximately 80% of all cases of skin cancer and is therefore an important health problem. In the Netherlands incidence rates are 165 for men and 157 for women per 100.000 person-years, and these rates are rising with 3-10% every year.
A simplified histological classification of BCCs includes the following three subtypes: nodular, superficial and infiltrative variants, with the nodular variant being the most frequent type. Although a characteristic feature of BCCs is their low risk to metastasize, if untreated they may be locally invasive and may induce considerable functional and cosmetic morbidity.
The gold standard treatment of all histological BCC subtypes is surgical excision (SE), but not all patients are eligible for surgery. In patients with multiple BCCs and older patients, surgery may lead to significant morbidity, and in some cases, it may result in disfiguring scarring. For these reasons and to reduce workload and costs in the healthcare system, there is a growing demand for alternative, non-invasive, treatments. An advantage of non-invasive treatment options is that they can be performed by other healthcare professionals, such as general practitioners and specialized nurses. For treatment of superficial BCCs (sBCC) non-invasive treatments, such as topical imiquimod (IMQ), 5-fluorouracil (5-FU) or photodynamic therapy (PDT) are already commonly used. Our group investigated the efficacy of those three therapies and found that after 3 years, BCCs treated with IMQ had a significant lower risk of recurrence, compared to the other therapies.
A recent study suggests that IMQ, besides being an immune-response modifier, also directly inhibits sonic hedgehog (SHH) signalling, the most important pathway active in BCCs. This targeted effect of IMQ very likely explains the superior therapeutic effect. Treatment of nodular BCC (nBCC) with IMQ has been investigated. Without prior curettage, high efficacy rates were found, although efficacy was still slightly inferior to SE.
The investigators hypothesize that the effectiveness of IMQ following prior curettage will not be inferior to SE and that the benefits will be a higher patient satisfaction and lower healthcare costs. A recently published discreet choice experiment showed that patients preferred IMQ to surgery regardless of previous experience of BCC symptoms and treatment.
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
- None
入排标准
- 年龄范围
- 18 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Adults aged 18 years or older
- •Primary histologically proven nodular BCC ≥ 4mm and ≤ 20mm in diameter. (If the tumour exhibits additional sBCC characteristics, but also contains nodular component that extend into the reticular dermis, the tumour will be classified as nBCC with superficial components and will be included).
- •Comorbidities may not interfere with study treatment
- •Capable to understand instructions
排除标准
- •A nodular BCC located in the H-zone of the face or hairy scalp
- •Recurrent (previously treated) nBCC
- •Aggressive BCC subtypes (morphoea, micronodular, or BCC with squamous differentiation)
- •Life expectancy of less than five years
- •Breast-feeding or pregnant women
- •Serious comorbidities
- •Use of immunosuppressive medication during the trial period or within 30 days before enrolment
- •Patients with genetic skin cancer disorders
研究组 & 干预措施
Standard surgical excision
Standard surgical "elliptical" excision including a 3-mm clinically tumour-free margin according to the current local hospital arrangements.
干预措施: Standard surgical excision (Procedure)
Imiquimod 5% cream with prior curettage
Tumours will be partially debulked under local anaesthesia by removing all tumour tissue until normal dermis remains with a blunt curette. After curettage patients will receive an instruction sheet to apply imiquimod 5% cream once daily, 5 days a week, during 6 weeks, starting one week after the curettage procedure. Patients will be instructed to apply a thin layer to the tumour including 5-10mm of the surrounding skin at least 1 hour before going to bed at night. The lesion will not be covered (unless needed because of weeping or bleeding). Participants will be asked to wash their hands after applying the cream, and to wipe the cream off after 8 hours (in the morning).
干预措施: Imiquimod 5% cream with prior curettage (Drug)
结局指标
主要结局
Proportion of participants tumour-free
时间窗: At 1 year after end of treatment
The primary study endpoint is the proportion of participants tumour-free at 1 year after end of treatment (defined as absence of initial treatment failure or any clinical signs of local recurrence). For SE, routine histological examination of haematoxylin and eosin (H\&E)-stained sections of the lateral and deep margins will be used to assess treatment failure. For curettage \& IMQ 5% cream, initial treatment failure will be clinically assessed at a follow-up visit 3 months after end of treatment. Initial treatment failure or any clinical signs of subsequent local recurrence will be assessed and recorded separately by one investigator. In case there is clinical suspicion of BCC, a 3 mm punch biopsy will be taken for histological verification.
次要结局
- The 5-year cumulative probability of recurrence free survival after end of treatment(At 5 years after end of treatment)
- Compliance(At 3 months after end of treatment)
- Cosmetic appearance(At 1 and 5 year after end of treatment)
- Patient satisfaction(At 1 and 5 year after end of treatment)
- Level of Pain(2 weeks after end of treatment)
- Cost-effectiveness(At 5 year after end of treatment)
- Adverse events(Up to 3 months after end of treatment)