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NCT Number: NCT06499415

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

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.

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Key information

Conditions

Actinic Keratoses Keratosis Keratosis, Actinic Neoplasms Precancerous Conditions Skin Diseases Skin and Connective Tissue Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Zuyderland Medical Center, Heerlen, Limburg, Netherlands

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

5FU-Calcipotriol

Drug

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

5-FU 50 MG/ML Topical Cream

Drug

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

Primary outcomes

  1. Treatment success at 12 months post-treatment

    Time frame: 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 outcomes

  1. AK clearance rate

    Time frame: 3 and 12 months after finishing treatment

    mean percentage change in AK lesions at 3 and 12 months post-treatment

  2. Recurrence rate

    Time frame: 3 and 12 months after finishing treatment

    New lesions and need for retreatment at 3 and 12 months post-treatment

  3. Adverse effects

    Time frame: During treatment and 3 months post-treatment

    Patients experiencing moderate to severe adverse effects

  4. Treatment compliance

    Time frame: During treatment

    Patients who are fully compliant to the prescribed treatment regimen (5FU-CAL or 5FU monotherapy)

  5. Patient satisfaction

    Time frame: 3 and 12 months post-treatment

    Patients who express to be satisfied with their treatment

  6. Quality of life before, during and after treatment

    Time frame: 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.

Other outcomes

  1. Long-term risk for cSCC

    Time frame: at least 3 years post-treatment

    The long-term probability of developing a cSCC

Study contacts

Contact information is provided by the study sponsor or research team.

Myrthe MG Moermans, MD

CONTACT

[email protected]

0031433877295

Sponsors and collaborators

Lead sponsor

Maastricht University Medical Center

Other

Registry information

Official study title

Combination Therapy of 5-Fluorouracil and CALcipotriol Versus 5-Fluorouracil in the Treatment of Actinic Keratosis: a Multicentre Randomized Controlled Clinical Trial

Acronym: CALM

Important dates

Study start
2024
Primary completion
2029
Study completion
2029
First posted
Jul 12, 2024
Registry last updated
May 11, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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