Combination Therapy of 5-Fluorouracil and CALcipotriol Versus 5-Fluorouracil in the Treatment of Actinic Keratosis

Phase 4

Recruiting

• Conditions: Actinic Keratoses
• Interventions: Drug: 5FU-Calcipotriol; Drug: 5-FU 50 MG/ML Topical Cream

• Registration Number: NCT06499415
• Lead Sponsor: Maastricht University Medical Center

Brief 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-07-05
• Study First Submitted QC: 2024-07-05
• Study First Posted: 2024-07-12
• Study Start: 2024-09-04
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-23
• Last Update Posted: 2024-10-26
• Primary Completion: 2029-03-02
• Study Completion: 2029-03-02

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 232

Inclusion Criteria

• 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

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Exclusion Criteria

• 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)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
topical 5FU-CAL, twice daily, during 4 or 6 consecutive days	5FU-Calcipotriol	Treatment duration is based on treatment location
topical 5FU, twice daily, 7 days a week, during 4 weeks	5-FU 50 MG/ML Topical Cream	-

Primary Outcome Measures

Name	Time	Method
Treatment success at 12 months post-treatment	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)

Secondary Outcome Measures

Name	Time	Method
AK clearance rate	3 and 12 months after finishing treatment	mean percentage change in AK lesions at 3 and 12 months post-treatment
Recurrence rate	3 and 12 months after finishing treatment	New lesions and need for retreatment at 3 and 12 months post-treatment
Adverse effects	During treatment and 3 months post-treatment	Patients experiencing moderate to severe adverse effects
Treatment compliance	During treatment	Patients who are fully compliant to the prescribed treatment regimen (5FU-CAL or 5FU monotherapy)
Patient satisfaction	3 and 12 months post-treatment	Patients who express to be satisfied with their treatment
Quality of life	Baseline, 1 week after finishing treatment and 3 and 12 months post-treatment	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.

Trial Locations

Locations (4)

Catharina Hospital Eindhoven; 🇳🇱 Eindhoven, Brabant, Netherlands

Zuyderland Medical Center; 🇳🇱 Heerlen, Limburg, Netherlands

Maastricht University Medical Center; 🇳🇱 Maastricht, Limburg, Netherlands

VieCuri Medical Center; 🇳🇱 Venlo, Limburg, Netherlands