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

Actinic Keratoses Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04875026
• Other study ID #: W00118 CR 401
• Secondary ID: 2020-000851-11
• Status: Completed
• Phase: Phase 4
• Start date: February 16, 2021
• Est. completion date: January 31, 2022

Study information

• Verified date: September 2022
• Source: Pierre Fabre Medicament
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 146
• Est. completion date: January 31, 2022
• Est. primary completion date: January 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

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

Related Conditions & MeSH terms

• Actinic Keratoses
• Keratosis
• Keratosis, Actinic

Intervention

Drug:
• 5-fluorouracil 4% (Tolak)
Application of Tolak once daily in the evening for 4 weeks

Device:
• Dexeryl
Application of Dexeryl once daily in the morning for 8 weeks

Locations

Country	Name	City	State
France	Private practice Maire	Arras
France	Chu de Nantes Hôtel-Dieu	Nantes
France	CHU Pau	Pau
France	CHU Poitiers	Poitiers
France	CHU St Etienne Hopital Nord	Saint-Étienne
Germany	Kath. Klinikum Bochum St. Josef-Hospital	Bochum
Germany	MVZ Dermatologisches Zentrum Bonn GmbH	Bonn
Germany	Private Practice Kurzen	Freising
Germany	Dermatologikum Hamburg	Hamburg
Germany	Private practice Quist	Mainz-Bretzenheim
Germany	CentroDerm Clinic	Witten
Germany	Hautarztpraxis	Witten
Italy	Uni Clinic Brescia	Brescia
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	Sapienza University of Rome - Polo Pontino	Terracina
Spain	Centre medic Congres	Barcelona
Spain	Hospital Alfredo Espinosa	Bilbao
Spain	Hospital Universitario Infanta Leonor	Madrid
Spain	Instituto Valenciano de Oncología,	Valencia
Spain	Hospital Marina Baixa	Villajoyosa

Sponsors (2)

Lead Sponsor	Collaborator
Pierre Fabre Medicament	Clinact

Countries where clinical trial is conducted

France,  Germany,  Italy,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Local Skin Reaction (LSR) total score	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).	at 4 weeks or Last Observation Carried Forward (LOCF)
Secondary	Local Skin Reaction (LSR) total score	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).	at 2 weeks (first follow-up)
Secondary	Local Skin Reaction (LSR) total score	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).	at 8 weeks (last follow up)
Secondary	Local Skin Reaction (LSR) items alone	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	at 2 weeks (first follow-up)
Secondary	Local Skin Reaction (LSR) items alone	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	at 4 weeks (second follow up)
Secondary	Local Skin Reaction (LSR) items alone	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	at 8 weeks (last follow up)
Secondary	Subjective signs at each visit	Patient questionnaire evaluating prurit (0-3), stinging/burning (0-3), pain (0-4). 0 is the best outcome, 10 is the worst outcome.	at 2 weeks (first follow-up)
Secondary	Subjective signs at each visit	Patient questionnaire evaluating prurit (0-3), stinging/burning (0-3), pain (0-4). 0 is the best outcome, 10 is the worst outcome.	at 4 weeks (second follow up)
Secondary	Subjective signs at each visit	Patient questionnaire evaluating prurit (0-3), stinging/burning (0-3), pain (0-4). 0 is the best outcome, 10 is the worst outcome.	at 8 weeks (last follow up)
Secondary	Local reactions according to Common Terminology Criteria for Adverse Event (CTCAE) grade 3 or 4	Intensity grading of adverse events	at 2 weeks (first follow-up)
Secondary	Local reactions according to Common Terminology Criteria for Adverse Event (CTCAE) grade 3 or 4	Intensity grading of adverse events	at 4 weeks (second follow up)
Secondary	Local reactions according to Common Terminology Criteria for Adverse Event (CTCAE) grade 3 or 4	Intensity grading of adverse events	at 8 weeks (last follow up)
Secondary	Adverse Events reported by patients or noticed by investigator		at 2, 4 and 8 weeks (first follow-up)
Secondary	Drop outs due to Adverse Events (AE) related to local skin reaction	discontinuation rate	at 2, 4 and 8 weeks (first follow-up)
Secondary	Use of rescue treatment		at 2 weeks (first follow-up)
Secondary	Use of rescue treatment		at 4 weeks (second follow up)
Secondary	Use of rescue treatment		at 8 weeks (last follow up)
Secondary	Treatment satisfaction (acceptability): measured by Treatment Satisfaction Questionnaire for Medication version 9 (TSQM-9)	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	at 4 weeks (end of treatment) or at Patient Withdrawal
Secondary	Treatment adherence	assessed by the participant using a self questionnaire	at 4 weeks
Secondary	Treatment adherence	assessed by the participant using a self questionnaire	at optional visit (when applicable), up to 8 weeks
Secondary	Health-related quality of life measured by actinic keratosis quality of life questionnaire (AKQoL)	actinic keratosis quality of life patient questionnaire, for Spain and Germany only. 0 is the best outcome, 27 is the worst outcome	at 8 weeks (last follow up)
Secondary	Rates of patients with complete and partial clearance rates		at 8 weeks (last follow up)
Secondary	Rates of patients with partial clearance rates		at 8 weeks (last follow up)
Secondary	Percentage change in number of AK lesions		at baseline
Secondary	Percentage change in number of AK lesions		at 2 weeks (first follow-up)
Secondary	Change in number of AK lesions		at 2 weeks (first follow-up)
Secondary	Percentage change in number of AK lesions		at 4 weeks (second follow up)
Secondary	Change in number of AK lesions		at 4 weeks (second follow up)
Secondary	Percentage change in number of AK lesions		at 8 weeks (last follow up)
Secondary	Change in number of AK lesions		at 8 weeks (last follow up)