Combination therapy of 5-Fluorouracil and Calcipotriol versus 5-Fluorouracil in the treatment of Actinic Keratosis: a multicentre randomized controlled clinical trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

University Hospital Maastricht

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17]

Trial duration

2 Sep 2024 → ongoing

Decision date (initial)

2024-06-13

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-511409-42-00

ClinicalTrials.gov

NCT06499415

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

The primary objective is to evaluate whether four or six day treatment with 5-Fluorouracil combined with calcipotriol is non-inferior to four weeks of 5-Fluorouracil monotherapy in terms of the 1-year probability of treatment success in patients with actinic keratosis. Treatment success is defined as ≥75% reduction in the number of AK lesions in the treatment area.

Secondary objectives 7

1. To compare the clearance rate in both treatment groups
2. To compare the recurrence rate in both groups
3. To compare adverse effects
4. To compare treatment compliance
5. To compare the patient satisfaction
6. To compare the quality of life
7. To investigate the long-term risk of cSCC development (exploratory objective)

Conditions and MedDRA coding

Actinic Keratosis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Adults above 18 years of age
2. Clinical and dermoscopical diagnosis of AK by a dermatologist, in one or more area(s): Face, ears, (balding) scalp OR Neck/Shawl area, including the sun-exposed chest area OR Upper extremities
3. Number of AK lesions ≥4 in a continuous treatment area of up to 100 cm2
4. AK Olsen grade I-III

Exclusion criteria 9

1. Previous field treatment for AK within 2cm of the treatment area, within 3 months
2. (non) melanoma skin cancer in treatment area
3. Mucosal lesions
4. Genetic skin cancer disorder
5. Women who are pregnant or breastfeeding
6. Previous allergy or intolerance to either 5Fluorouracil or calcipotriol
7. Patients with known contra-indications for calcipotriol use: previous diagnosis of hyper-calcemia, disturbed calcium metabolism, severe kidney or liver dysfunction
8. Concurrent use of oral capecitabine or any other topical or systemic chemopreventive agent for any indication
9. Limited understanding of the Dutch language and not being able to give informed consent

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The main trial endpoint is the proportion of patients achieving treatment success at 12 months post-treatment. Treatment success is defined as ≥75% reduction in the number of AK lesions in the treatment area (partial clearance).

Secondary endpoints 11

1. The proportion of patients achieving treatment success at 3 months post-treatment. Treatment success is defined as ≥75% reduction in the number of AK lesions in the treatment area (partial clearance).
2. The proportion of patients achieving 100% clearance of AK lesions (complete clearance) at 3 and 12 months post-treatment.
3. The mean percentage change in AK lesions compared to baseline, measured at 3 and 12 months post-treatment
4. The mean change in Actinic Keratosis Area and Severity Index (AKASI) score compared to baseline, measured at 3 and 12 months post-treatment
5. Recurrence rate, defined as the proportion of patients with new lesions at 3 and 12 months post-treatment
6. The proportion of patients who need retreatment within 12 months after finishing treatment
7. The proportion of patients experiencing moderate to severe adverse effects, as reported by the patients in their treatment diary and at 3 months post-treatment.
8. Patient satisfaction with treatment at 3 and 12 months post-treatment, expressed as the proportion of patients who indicate to be satisfied with their treatment.
9. Mean score for quality of life on the Skindex-17 questionnaire at baseline, 1 week after finishing treatment and 3 and 12 months post-treatment.
10. Treatment adherence expressed as proportion of patients with complete adherence to the prescribed treatment regimen.
11. Exploratory endpoint: the long-term probability of cSCC development, expressed as the 3-year cumulative probability of cSCC development.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

University Hospital Maastricht

Sponsor organisation

University Hospital Maastricht

Address

P Debyelaan 25

City

Maastricht

Postcode

6229 HX

Country

Netherlands

Scientific contact point

Organisation

University Hospital Maastricht

Contact name

drs. M.M.G. Moermans

Public contact point

Organisation

University Hospital Maastricht

Contact name

drs. M.M.G. Moermans

Locations

1 EU/EEA country · 4 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 17 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications