Clinical trial NCT04875026: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Actinic Keratoses
Lead sponsor: Pierre Fabre Medicament
Sponsor class: INDUSTRY
Collaborators: name: Clinact
First posted: 2021-05-06
Enrollment: 146
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.


Eligibility criteria: 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

Primary outcomes:
measure: Local Skin Reaction (LSR) total score
timeFrame: at 4 weeks or Last Observation Carried Forward (LOCF)
Secondary outcomes:
measure: Local Skin Reaction (LSR) total score
timeFrame: at 2 weeks (first follow-up)
measure: Local Skin Reaction (LSR) total score
timeFrame: at 8 weeks (last follow up)
measure: Local Skin Reaction (LSR) items alone
timeFrame: at 2 weeks (first follow-up)
measure: Local Skin Reaction (LSR) items alone
timeFrame: at 4 weeks (second follow up)
measure: Local Skin Reaction (LSR) items alone
timeFrame: at 8 weeks (last follow up)
measure: Subjective signs at each visit
timeFrame: at 2 weeks (first follow-up)
measure: Subjective signs at each visit
timeFrame: at 4 weeks (second follow up)
measure: Subjective signs at each visit
timeFrame: at 8 weeks (last follow up)
measure: Local reactions according to Common Terminology Criteria for Adverse Event (CTCAE) grade 3 or 4
timeFrame: at 2 weeks (first follow-up)
measure: Local reactions according to Common Terminology Criteria for Adverse Event (CTCAE) grade 3 or 4
timeFrame: at 4 weeks (second follow up)
measure: Local reactions according to Common Terminology Criteria for Adverse Event (CTCAE) grade 3 or 4
timeFrame: at 8 weeks (last follow up)
measure: Adverse Events reported by patients or noticed by investigator
timeFrame: at 2, 4 and 8 weeks (first follow-up)
measure: Drop outs due to Adverse Events (AE) related to local skin reaction
timeFrame: at 2, 4 and 8 weeks (first follow-up)
measure: Use of rescue treatment
timeFrame: at 2 weeks (first follow-up)
measure: Use of rescue treatment
timeFrame: at 4 weeks (second follow up)
measure: Use of rescue treatment
timeFrame: at 8 weeks (last follow up)
measure: Treatment satisfaction (acceptability): measured by Treatment Satisfaction Questionnaire for Medication version 9 (TSQM-9)
timeFrame: at 4 weeks (end of treatment) or at Patient Withdrawal
measure: Treatment adherence
timeFrame: at 4 weeks
measure: Treatment adherence
timeFrame: at optional visit (when applicable), up to 8 weeks
measure: Health-related quality of life measured by actinic keratosis quality of life questionnaire (AKQoL)
timeFrame: at 8 weeks (last follow up)
measure: Rates of patients with complete and partial clearance rates
timeFrame: at 8 weeks (last follow up)
measure: Rates of patients with partial clearance rates
timeFrame: at 8 weeks (last follow up)
measure: Percentage change in number of AK lesions
timeFrame: at baseline
measure: Percentage change in number of AK lesions
timeFrame: at 2 weeks (first follow-up)
measure: Change in number of AK lesions
timeFrame: at 2 weeks (first follow-up)
measure: Percentage change in number of AK lesions
timeFrame: at 4 weeks (second follow up)
measure: Change in number of AK lesions
timeFrame: at 4 weeks (second follow up)
measure: Percentage change in number of AK lesions
timeFrame: at 8 weeks (last follow up)
measure: Change in number of AK lesions
timeFrame: at 8 weeks (last follow up)
Other outcomes:
Locations:
city: Arras
country: France
facility: Private practice Maire
city: Nantes
country: France
facility: Chu de Nantes Hôtel-Dieu
city: Pau
country: France
facility: CHU Pau
city: Poitiers
country: France
facility: CHU Poitiers
city: Saint-Étienne
country: France
facility: CHU St Etienne Hopital Nord
city: Bochum
country: Germany
facility: Kath. Klinikum Bochum St. Josef-Hospital
city: Bonn
country: Germany
facility: MVZ Dermatologisches Zentrum Bonn GmbH
city: Freising
country: Germany
facility: Private Practice Kurzen
city: Hamburg
country: Germany
facility: Dermatologikum Hamburg
city: Mainz-Bretzenheim
country: Germany
facility: Private practice Quist
city: Witten
country: Germany
facility: Hautarztpraxis
city: Witten
country: Germany
facility: CentroDerm Clinic
city: Brescia
country: Italy
facility: Uni Clinic Brescia
city: Catania
country: Italy
facility: Uni Clinic Catania
city: Coppito
country: Italy
facility: Uni Clinic L'Aquila
city: Genova
country: Italy
facility: Policlinico San Martino
city: Messina
country: Italy
facility: University of Messina
city: Modena
country: Italy
facility: Uni Clinic Modena
city: Napoli
country: Italy
facility: NAPLES VANVITELLI UNIVERSITI (Federico II Hospital)
city: Reggio Emilia
country: Italy
facility: Azienda Unità Sanitaria Locale - IRCCS
city: Roma
country: Italy
facility: Catholic University Fondazione Policlinico Universitario A. Gemelli
city: Terracina
country: Italy
facility: Sapienza University of Rome - Polo Pontino
city: Barcelona
country: Spain
facility: Centre medic Congres
city: Bilbao
country: Spain
facility: Hospital Alfredo Espinosa
city: Madrid
country: Spain
facility: Hospital Universitario Infanta Leonor
city: Valencia
country: Spain
facility: Instituto Valenciano de Oncología,
city: Villajoyosa
country: Spain
facility: Hospital Marina Baixa
Study officials:
affiliation: Kath. Klinikum Bochum St. Josef-Hospital
name: Eggert STOCKFLETH, Pr.
role: PRINCIPAL_INVESTIGATOR
References: