Clinical trial NCT06499415: Combination Therapy of 5-Fluorouracil and CALcipotriol Versus 5-Fluorouracil in the Treatment of Actinic Keratosis
Official title: Combination Therapy of 5-Fluorouracil and CALcipotriol Versus 5-Fluorouracil in the Treatment of Actinic Keratosis: a Multicentre Randomized Controlled Clinical Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Actinic Keratoses
Keywords: 5-Fluorouracil
Calcipotriol
Lead sponsor: Maastricht University Medical Center
Sponsor class: OTHER
First posted: 2024-07-12
Enrollment: 232
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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)

Primary outcomes:
measure: Treatment success at 12 months post-treatment
timeFrame: 12 months after finishing treatment
Secondary outcomes:
measure: AK clearance rate
timeFrame: 3 and 12 months after finishing treatment
measure: Recurrence rate
timeFrame: 3 and 12 months after finishing treatment
measure: Adverse effects
timeFrame: During treatment and 3 months post-treatment
measure: Treatment compliance
timeFrame: During treatment
measure: Patient satisfaction
timeFrame: 3 and 12 months post-treatment
measure: Quality of life before, during and after treatment
timeFrame: Baseline, 1 week after finishing treatment and 3 and 12 months post-treatment
Other outcomes:
measure: Long-term risk for cSCC
timeFrame: at least 3 years post-treatment
Locations:
city: Eindhoven
country: Netherlands
facility: Catharina Hospital Eindhoven
state: Brabant
city: Heerlen
country: Netherlands
facility: Zuyderland Medical Center
state: Limburg
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Center
state: Limburg
city: Venlo
country: Netherlands
facility: VieCuri Medical Center
state: Limburg
Study officials:
References: