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

NCT ID: NCT06499415

Last Updated: 2025-05-11

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 232 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-09-04
• Study Completion Date: 2029-03-02

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.

Conditions

Actinic Keratoses

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

topical 5FU-CAL, twice daily, during 4 or 6 consecutive days

Treatment duration is based on treatment location

Group Type: EXPERIMENTAL

5FU-Calcipotriol

Intervention Type: DRUG

topical 5FU-CAL, twice daily, during 4 or 6 consecutive days, depending on the treatment location

topical 5FU, twice daily, 7 days a week, during 4 weeks

Group Type: ACTIVE_COMPARATOR

5-FU 50 MG/ML Topical Cream

Intervention Type: DRUG

topical 5FU, twice daily, 7 days a week, during 4 weeks

Interventions

5FU-Calcipotriol

topical 5FU-CAL, twice daily, during 4 or 6 consecutive days, depending on the treatment location

Intervention Type: DRUG

5-FU 50 MG/ML Topical Cream

topical 5FU, twice daily, 7 days a week, during 4 weeks

Intervention Type: DRUG

Eligibility Criteria

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

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Maastricht University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Zuyderland Medical Center

Heerlen, Limburg, Netherlands

Site Status: RECRUITING

Maastricht University Medical Center

Maastricht, Limburg, Netherlands

Site Status: RECRUITING

VieCuri Medical Center

Venlo, Limburg, Netherlands

Site Status: RECRUITING

Catharina Hospital Eindhoven

Eindhoven, North Brabant, Netherlands

Site Status: RECRUITING

Countries

Netherlands

Central Contacts

Myrthe MG Moermans, MD

Role: CONTACT

myrthe.moermans@mumc.nl

0031433877295

Facility Contacts

Myrthe MG Moermans, MD

Role: primary

myrthe.moermans@mumc.nl

0031433877295

Myrthe MG Moermans, MD

Role: primary

myrthe.moermans@mumc.nl

0031433877295

Myrthe MG Moermans, MD

Role: primary

myrthe.moermans@mumc.nl

0031433877295

Myrthe MG Moermans, MD

Role: primary

myrthe.moermans@mumc.nl

0031433877295

Other Identifiers

2024-511409-42-00

Identifier Type: -

Identifier Source: org_study_id