Frequency and Intensity of Local Reactions in Patients Treated With 4% 5-FU vs 4% 5-FU Associated With an Emollient Cream: a Randomised, Controlled Clinical Trial

Phase 4

Completed

• Conditions: Actinic Keratoses
• Interventions: Drug: 5-fluorouracil 4% (Tolak); Device: Dexeryl

• Registration Number: NCT04875026
• Lead Sponsor: Pierre Fabre Medicament

Brief Summary

Transient local skin reactions with topical Actinic Keratosis treatments such as 5-FluoroUracil (5-FU) often lead to non-adhesion from patients and thus to treatment failure. In regards to 5-FU treatment, these local reactions are related to the pharmacological action of the molecule. The current therapeutic challenge is to reduce the local reactions induced by 5-FU without interfering with its efficacy, in particular by the use of an emollient cream.

The aim of the present study is to investigate how the use of an emollient, namely Dexeryl, could improve the local skin reactions occurring during 4 weeks of a 4% 5-FU treatment.

Detailed Description

Not available

Study Timeline

• Study Start: 2021-02-16
• Study First Submitted: 2021-03-18
• Study First Submitted QC: 2021-04-30
• Study First Posted: 2021-05-06
• Primary Completion: 2022-01-31
• Study Completion: 2022-01-31
• Status Verified: 2022-09
• Last Update Submitted: 2022-09-15
• Last Update Posted: 2022-09-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 146

Inclusion Criteria

Participants are eligible only if all of the following criteria apply:

Age

1. Participant must be more than 18 years old inclusive, at the time of signing the informed consent.

   Type of Participant and Disease Characteristics

2. Individuals with a clinical diagnosis of actinic keratosis (AK).

3. Individuals harboring 5 or more clinically recognizable (palpable and/or visible to unaided eye) AK lesions of the face, and/or ears and/or scalp. The AK lesions must be clinically typical non hypertrophic and/or nonhyperkeratotic.

4. Subject in good general condition and free of any disease state or condition which, in the investigator's opinion, could impair evaluation of actinic keratosis or could expose the subject to an unacceptable risk by study participation.

   Sex

5. Male or female. A Female participant is eligible to participate if she is not a woman of childbearing potential (WOCBP), defined as postmenopausal (cessation of menses >12 months) or surgically sterile (history of bilateral tubal ligation, bilateral oophorectomy, total hysterectomy).

   Informed Consent

6. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

   Ethical/Legal considerations

7. Affiliated to a social security system, or is a beneficiary (if applicable in the national regulation).

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Exclusion Criteria

Participants are excluded from the study if any of the following criteria apply:

Medical Conditions

1. With AK lesions within treatment areas which are hyperkeratotic or which are clinically suspected to be squamous cell carcinoma (SCC).

2. With pre-existing local skin reactions with a total score ≥ 3.

3. History of hypersensitivity to the ingredients of Tolak® or Dexeryl®.

4. With a known allergy to peanut or soya.

5. Non postmenopausal or non surgically sterile woman considered as WOCBP, pregnant or breastfeeding women.

   Prior/Concomitant Therapy

6. Under systemic 5-fluorouracil or any systemic cancer treatment within eight weeks prior to the study.

7. Under any other topical AK treatments or therapies (e.g., Cryotherapy or Photodynamic therapy) in the treatment area(s) within eight weeks prior to starting the study.

8. Treated with systemic steroids, immunosuppressants or immunomodulators within four weeks prior to the study.

9. Under prescription retinoids or topical steroids in the treatment area(s) within four weeks prior to the study.

10. With known dihydropyrimidinedehydrogénase (DPD) deficiency or under treatment with brivudine, sorivudine or analogues within 4 weeks prior to starting the study.

11. Treated with glycolic acid products and alpha-hydroxy products in the treatment area(s) within four weeks prior to starting the study.

12. Treated with chemical peeling products in the treatment area(s) within eight weeks prior to starting the study.

    Prior/Concurrent Clinical Study Experience

13. Is participating in another clinical trial

14. Has participated in another clinical trial within the last 30 days, has received treatment with known remnant effects or undergone investigation liable to interfere with the present clinical trial Other Exclusions

15. Is a family member of the Investigator or any associate, colleague, and employee assisting in the conduct of the study (secretary, nurse, technician,...)

16. Is in a position likely to represent a conflict of interest

17. Has forfeited his / her freedom by administrative or legal award or is under guardianship

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
5-fluorouracil 4% (Tolak) + Dexeryl	5-fluorouracil 4% (Tolak)	This group will apply 5-FU once daily for 4 weeks, and Dexeryl once daily for 8 weeks.
5-fluorouracil 4% (Tolak)	5-fluorouracil 4% (Tolak)	This group will only apply 5-FU once daily for 4 weeks.
5-fluorouracil 4% (Tolak) + Dexeryl	Dexeryl	This group will apply 5-FU once daily for 4 weeks, and Dexeryl once daily for 8 weeks.

Primary Outcome Measures

Name	Time	Method
Local Skin Reaction (LSR) total score	at 4 weeks or Last Observation Carried Forward (LOCF)	Investigator-assessed score: 6 objective items scored from 0-4 (erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, erosion/ulceration) for a minimal score of 0 (best outcome possible), and a maximal score of 24 (worst outcome possible).

Secondary Outcome Measures

Name	Time	Method
Rates of patients with complete and partial clearance rates	at 8 weeks (last follow up)
Rates of patients with partial clearance rates	at 8 weeks (last follow up)
Percentage change in number of AK lesions	at 8 weeks (last follow up)
Treatment satisfaction (acceptability): measured by Treatment Satisfaction Questionnaire for Medication version 9 (TSQM-9)	at 4 weeks (end of treatment) or at Patient Withdrawal	The TSQM-9 questionnaire includes nine questions that assess patients' satisfaction by providing score on three scales: effectiveness (questions 1 to 3), convenience (questions 4 to 6) and global satisfaction (questions 7 to 9). The scores of each scale range from 0 to 100, where a higher score indicates a greater satisfaction
Local Skin Reaction (LSR) total score	at 8 weeks (last follow up)	Investigator-assessed score: 6 objective items scored from 0-4 (erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, erosion/ulceration) for a minimal score of 0 (best outcome possible), and a maximal score of 24 (worst outcome possible).
Subjective signs at each visit	at 8 weeks (last follow up)	Patient questionnaire evaluating prurit (0-3), stinging/burning (0-3), pain (0-4). 0 is the best outcome, 10 is the worst outcome.
Local reactions according to Common Terminology Criteria for Adverse Event (CTCAE) grade 3 or 4	at 8 weeks (last follow up)	Intensity grading of adverse events
Drop outs due to Adverse Events (AE) related to local skin reaction	at 2, 4 and 8 weeks (first follow-up)	discontinuation rate
Use of rescue treatment	at 8 weeks (last follow up)
Treatment adherence	at optional visit (when applicable), up to 8 weeks	assessed by the participant using a self questionnaire
Health-related quality of life measured by actinic keratosis quality of life questionnaire (AKQoL)	at 8 weeks (last follow up)	actinic keratosis quality of life patient questionnaire, for Spain and Germany only. 0 is the best outcome, 27 is the worst outcome
Change in number of AK lesions	at 8 weeks (last follow up)
Local Skin Reaction (LSR) items alone	at 8 weeks (last follow up)	Presence/absence/intensity of each item of the LSR: 6 objective items scored from 0-4 (erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, erosion/ulceration). For each item, 0 is the best outcome possible, 4 is the worst
Adverse Events reported by patients or noticed by investigator	at 2, 4 and 8 weeks (first follow-up)

Trial Locations

Locations (27)

Kath. Klinikum Bochum St. Josef-Hospital; 🇩🇪 Bochum, Germany

MVZ Dermatologisches Zentrum Bonn GmbH; 🇩🇪 Bonn, Germany

CHU St Etienne Hopital Nord; 🇫🇷 Saint-Étienne, France

Private Practice Kurzen; 🇩🇪 Freising, Germany

Hautarztpraxis; 🇩🇪 Witten, Germany

Chu de Nantes Hôtel-Dieu; 🇫🇷 Nantes, France

Private practice Quist; 🇩🇪 Mainz-Bretzenheim, Germany

Centre medic Congres; 🇪🇸 Barcelona, Spain

Instituto Valenciano de Oncología,; 🇪🇸 Valencia, Spain

Private practice Maire; 🇫🇷 Arras, France

Dermatologikum Hamburg; 🇩🇪 Hamburg, Germany

CHU Pau; 🇫🇷 Pau, France

CHU Poitiers; 🇫🇷 Poitiers, France

Hospital Universitario Infanta Leonor; 🇪🇸 Madrid, Spain

Hospital Alfredo Espinosa; 🇪🇸 Bilbao, Spain

Hospital Marina Baixa; 🇪🇸 Villajoyosa, Spain

Uni Clinic Brescia; 🇮🇹 Brescia, Italy

Sapienza University of Rome - Polo Pontino; 🇮🇹 Terracina, Italy

Uni Clinic Catania; 🇮🇹 Catania, Italy

Uni Clinic L'Aquila; 🇮🇹 Coppito, Italy

Policlinico San Martino; 🇮🇹 Genova, Italy

University of Messina; 🇮🇹 Messina, Italy

Uni Clinic Modena; 🇮🇹 Modena, Italy

NAPLES VANVITELLI UNIVERSITI (Federico II Hospital); 🇮🇹 Napoli, Italy

Azienda Unità Sanitaria Locale - IRCCS; 🇮🇹 Reggio Emilia, Italy

Catholic University Fondazione Policlinico Universitario A. Gemelli; 🇮🇹 Roma, Italy

CentroDerm Clinic; 🇩🇪 Witten, Germany