Combination Therapy of 5-Fluorouracil and CALcipotriol Versus 5-Fluorouracil in the Treatment of Actinic Keratosis: a Multicentre Randomized Controlled Clinical Trial
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 232
- 试验地点
- 4
- 主要终点
- Treatment success at 12 months post-treatment
研究概览
简要总结
5-Fluorouracil (5FU) is proven to be the most effective therapy in field directed treatment for AK, with Jansen et al. reporting a 1-year probability of treatment success of 74.7%. However, treatment with 5FU is associated with side effects, like erythema, itching, a burning sensation and crusting, and a burdensome dosing regimen of twice daily application for four weeks. This long treatment duration in combination with side-effects and overall lifestyle adjustments during treatment can be the reason for poor adherence and premature termination, and it can also lead to future refusal of 5FU therapy. Therefore, room for improvement lies in increasing the tolerability, in terms of side effects or treatment duration, while maintaining the efficacy of 5FU in the treatment of AK.
Addition therapy, which can shorten the duration of treatment, might be the key to success. Calcipotriol (CAL) enhances thymic stromal lymphopoietin (TSLP), an epithelium-derived cytokine, which promotes antitumor immunity. Therefore, it is known to have a synergistic effect when combined with 5FU in the treatment of AK. This suggests that short-term treatment with 5FU-CAL is effective and provides the opportunity to shorten duration of treatment, thereby improving tolerability of treatment and full adherence to the treatment regimen.
However, no study compared 5FU-CAL combination therapy with standard 5FU treatment for a duration of 28 days. This study aims to evaluate whether a short course of combination therapy with 5FU-CAL is non-inferior to a full course of 5FU monotherapy with respect to the 1-year probability of treatment success.
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
- Double (Investigator, Outcomes Assessor)
盲法说明
The investigator, who is also a physician and will evaluate treatment effect, is blinded to the allocated treatment
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 above 18 years of age
- •Clinical and dermoscopical diagnosis of AK by a dermatologist, in one or more area(s):
- •Face, ears, (balding) scalp
- •Neck/Shawl area, including the sun-exposed chest area
- •Upper extremities
- •Number of AK lesions ≥4 in a continuous treatment area of up to 100 cm2
- •AK Olsen grade I-III
排除标准
- •Previous field treatment for AK within 2cm of the treatment area, within 3 months
- •(non) melanoma skin cancer in treatment area
- •Mucosal lesions
- •Genetic skin cancer disorder
- •Women who are pregnant or breastfeeding
- •Women of childbearing potential, who are not willing to use effective contraceptive measures
- •Previous allergy or intolerance to either 5FU or calcipotriol
- •Patients with known contra-indications for calcipotriol use: previous diagnosis of hyper-calcemia, disturbed calcium metabolism, severe kidney or liver dysfunction
- •Concurrent use of oral capecitabine or any other topical or systemic chemopreventive agent for any indication
- •Concurrent use of other topical treatments registered as treatment for AK
- •Limited understanding of the Dutch language and not being able to give informed consent (incapacitated patients)
研究组 & 干预措施
topical 5FU-CAL, twice daily, during 4 or 6 consecutive days
Treatment duration is based on treatment location
干预措施: 5FU-Calcipotriol (Drug)
topical 5FU, twice daily, 7 days a week, during 4 weeks
干预措施: 5-FU 50 MG/ML Topical Cream (Drug)
结局指标
主要结局
Treatment success at 12 months post-treatment
时间窗: 12 months after finishing treatment
Treatment success at 12 months post treatment, defined as ≥75% reduction in the number of AK lesions in the treatment area (partial clearance)
次要结局
- AK clearance rate(3 and 12 months after finishing treatment)
- Recurrence rate(3 and 12 months after finishing treatment)
- Adverse effects(During treatment and 3 months post-treatment)
- Treatment compliance(During treatment)
- Patient satisfaction(3 and 12 months post-treatment)
- Quality of life before, during and after treatment(Baseline, 1 week after finishing treatment and 3 and 12 months post-treatment)