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

NCT06499415 | Recruiting Phase 4

• 1 other identifier: 2024-511409-42-00
• Study Type: interventional
• Target: 232
• Locations: 1 country
• Sites: 4

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

Keywords

5-Fluorouracil; Calcipotriol

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• 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

Other Outcomes (1)

• Long-term risk for cSCC

  at least 3 years post-treatment

Study Arms (2)

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

EXPERIMENTAL

Treatment duration is based on treatment location

Drug: 5FU-Calcipotriol

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

ACTIVE COMPARATOR

Drug: 5-FU 50 MG/ML Topical Cream

Interventions

5FU-Calcipotriol DRUG

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

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

5-FU 50 MG/ML Topical Cream DRUG

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

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Maastricht University Medical Center: lead

Study Sites (4)

Zuyderland Medical Center

Heerlen, Limburg, 6419 HC, Netherlands

RECRUITING

Maastricht University Medical Center

Maastricht, Limburg, 6229 HX, Netherlands

RECRUITING

VieCuri Medical Center

Venlo, Limburg, 5912 BL, Netherlands

RECRUITING

Catharina Hospital Eindhoven

Eindhoven, North Brabant, 5623 EJ, Netherlands

RECRUITING

MeSH Terms

Conditions

Keratosis, Actinic

Interventions

Fluorouracil

Condition Hierarchy (Ancestors)

Precancerous Conditions; Neoplasms; Keratosis; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Central Study Contacts

Myrthe MG Moermans, MD

CONTACT

0031433877295; myrthe.moermans@mumc.nl

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The investigator, who is also a physician and will evaluate treatment effect, is blinded to the allocated treatment
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 5, 2024
• First Posted: July 12, 2024
• Study Start: September 4, 2024
• Primary Completion (Estimated): March 2, 2029
• Study Completion (Estimated): March 2, 2029
• Last Updated: May 11, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

NL (4)