Actinic KeratosesPhase 4CALMNCT06499415
Combination Therapy of 5-Fluorouracil and CALcipotriol Versus 5-Fluorouracil in the Treatment of Actinic Keratosis
A Phase 4 study testing 5FU-Calcipotriol and 5-FU 50 MG/ML Topical Cream in people with Actinic Keratoses, run by Maastricht University Medical Center at 4 sites in Netherlands.
Trial 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%. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Actinic Keratoses
- What is being tested?
- 5FU-Calcipotriol and 5-FU 50 MG/ML Topical Cream
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 232 participants
- Where
- 4 sitesNetherlands
- Study dates
- 4 Sep 2024to 1 Sep 2026
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 11Show fewer
- 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)
Trial locations and contacts
4 sites in 1 country.
Netherlands4 sites
Catharina Hospital Eindhoven
Eindhoven, North Brabant, 5623 EJ
Zuyderland Medical Center
Heerlen, Limburg, 6419 HC
Maastricht University Medical Center
Maastricht, Limburg, 6229 HX
VieCuri Medical Center
Venlo, Limburg, 5912 BL
About this study
Official title: Combination Therapy of 5-Fluorouracil and CALcipotriol Versus 5-Fluorouracil in the Treatment of Actinic Keratosis: a Multicentre Randomized Controlled Clinical Trial
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
- Being tested
- 5FU-Calcipotriol, 5-FU 50 MG/ML Topical Cream
- Keywords
- 5-Fluorouracil, Calcipotriol
- Medical subject headings
- Keratosis, Actinic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
5FU-CalcipotriolDrug
topical 5FU-CAL, twice daily, during 4 or 6 consecutive days, depending on the treatment location
5-FU 50 MG/ML Topical CreamDrug
topical 5FU, twice daily, 7 days a week, during 4 weeks
| Study group | Role | What they receive |
|---|---|---|
| topical 5FU-CAL, twice daily, during 4 or 6 consecutive days | Experimental | Treatment duration is based on treatment location Receives: Drug: 5FU-Calcipotriol |
| topical 5FU, twice daily, 7 days a week, during 4 weeks | Active comparator | Not described Receives: Drug: 5-FU 50 MG/ML Topical Cream |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 12 months after finishing treatment
Secondary outcomes (6)
AK clearance rate
mean percentage change in AK lesions at 3 and 12 months post-treatment
Measured: 3 and 12 months after finishing treatment
Recurrence rate
New lesions and need for retreatment at 3 and 12 months post-treatment
Measured: 3 and 12 months after finishing treatment
Adverse effects
Patients experiencing moderate to severe adverse effects
Measured: During treatment and 3 months post-treatment
Treatment compliance
Patients who are fully compliant to the prescribed treatment regimen (5FU-CAL or 5FU monotherapy)
Measured: During treatment
Patient satisfaction
Patients who express to be satisfied with their treatment
Measured: 3 and 12 months post-treatment
Quality of life before, during and after 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.
Measured: Baseline, 1 week after finishing treatment and 3 and 12 months post-treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jul 2024
- Study start4 Sep 2024
- Primary completion1 Sep 2026
- Study completion1 Sep 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Actinic KeratosesStudies of the same condition, open and under way.
- More trials run by Maastricht University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 232 participants (actual)
Sponsor and investigators
- Lead sponsor
- Maastricht University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06499415
- Sponsor's protocol ID
- 2024-511409-42-00
- Acronym
- CALM
- Status last verified
- Oct 2026
- First submitted
- 5 Jul 2024
- Last updated
- 29 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Combination Therapy of 5-Fluorouracil and CALcipotriol Versus 5-Fluorouracil in the Treatment of Actinic Keratosis: a Multicentre Randomized Controlled Clinical Trial
- ClinicalTrials.gov ID
- NCT06499415
- Acronym / sponsor ID
- CALM / 2024-511409-42-00
- Conditions
- Actinic Keratoses
- Keywords
- 5-Fluorouracil, Calcipotriol
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 232 participants (actual)
- Lead sponsor
- Maastricht University Medical CenterUniversity, hospital or other
- Study start
- 4 Sep 2024 (actual)
- Primary completion
- 1 Sep 2026 (actual)
- Study completion
- 1 Sep 2026 (actual)
- First posted
- 12 Jul 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| topical 5FU-CAL, twice daily, during 4 or 6 consecutive days | Experimental | Drug: 5FU-CalcipotriolTreatment duration is based on treatment location |
| topical 5FU, twice daily, 7 days a week, during 4 weeks | Active comparator | Drug: 5-FU 50 MG/ML Topical Cream |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Adults above 18 years of age
- Clinical and dermoscopical diagnosis of AK by a dermatologist, in one or more area(s):
- Number of AK lesions ≥4 in a continuous treatment area of up to 100 cm2
- AK Olsen grade I-III
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 5FU-Calcipotrioltopical 5FU-CAL, twice daily, during 4 or 6 consecutive days, depending on the treatment location | Drug | topical 5FU-CAL, twice daily, during 4 or 6 consecutive days |
| 5-FU 50 MG/ML Topical Creamtopical 5FU, twice daily, 7 days a week, during 4 weeks | Drug | topical 5FU, twice daily, 7 days a week, during 4 weeks |
Primary outcome
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)
6 secondary outcomes
AK clearance rate
Time frame: 3 and 12 months after finishing treatment
Recurrence rate
Time frame: 3 and 12 months after finishing treatment
Adverse effects
Time frame: During treatment and 3 months post-treatment
Treatment compliance
Time frame: During treatment
Patient satisfaction
Time frame: 3 and 12 months post-treatment
Quality of life before, during and after treatment
Time frame: Baseline, 1 week after finishing treatment and 3 and 12 months post-treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Oct 2026.
- Individual participant dataSharing planned: No
Related trials for Actinic Keratoses
RecruitingPhase 3
Study of Reformulated Levulan Kerastick Plus PDT for Actinic Keratosis on Upper Extremities
Actinic Keratosis
RecruitingPhase 3
Study of Reformulated Levulan Kerastick Plus PDT for Actinic Keratosis on Face and Scalp
Actinic Keratosis
Active, not recruitingPhase 3
A Pilot Clinical Trial Comparing Topical Fluorouracil to Fluorouracil Plus Calcipotriene Field Treatments in Patients With Multiple Actinic Keratoses
Multiple Actinic Keratoses
RecruitingPhase 3
Basal Cell Carcinoma Chemoprevention Trial
Basal Cell Carcinoma
Active, not recruitingPhase 4
Cryotherapy in Combination With Red Light PDT for Actinic Keratosis of Full Face
Actinic Keratoses
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing 5FU-Calcipotriol and 5-FU 50 MG/ML Topical Cream in people with Actinic Keratoses, run by Maastricht University Medical Center at 4 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Treatment success at 12 months post-treatment (time frame: 12 months after finishing treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Oct 2026.