Combination Therapy of 5-Fluorouracil and CALcipotriol Versus 5-Fluorouracil in the Treatment of Actinic Keratosis
NCT Number: NCT06499415
Acronym: CALM
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE4
Conditions: Actinic Keratoses
Interventions: DRUG: 5FU-Calcipotriol|DRUG: 5-FU 50 MG/ML Topical Cream
Sponsor: Maastricht University Medical Center
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 232
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: DOUBLE (INVESTIGATOR, OUTCOMES_ASSESSOR)|Primary Purpose: TREATMENT
Start Date: 2024-09-02
Completion Date: 2029-03-02

Summary:
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.

Primary Outcome Measures: Treatment success at 12 months post-treatment, Treatment success at 12 months post treatment, defined as ≥75% reduction in the number of AK lesions in the treatment area (partial clearance), 12 months after finishing treatment
Secondary Outcome Measures: AK clearance rate, mean percentage change in AK lesions at 3 and 12 months post-treatment, 3 and 12 months after finishing treatment|Recurrence rate, New lesions and need for retreatment at 3 and 12 months post-treatment, 3 and 12 months after finishing treatment|Adverse effects, Patients experiencing moderate to severe adverse effects, During treatment and 3 months post-treatment|Treatment compliance, Patients who are fully compliant to the prescribed treatment regimen (5FU-CAL or 5FU monotherapy), During treatment|Patient satisfaction, Patients who express to be satisfied with their treatment, 3 and 12 months post-treatment|Quality of life, The mean score for quality of life on the Skindex-17 questionnaire. The Skindex-17 questionnaire has 17 items investigating the quality of life on different domains. The questions are answered on a five-point scale. A higher score represents a higher impact on QoL., Baseline, 1 week after finishing treatment and 3 and 12 months post-treatment
Other Outcome Measures: Long-term risk for cSCC, The long-term probability of developing a cSCC, at least 3 years post-treatment