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

Pierre Fabre Medicament146 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

SUPPORTIVE_CARE

Masking

SINGLE

Enrollment

146

Conditions

Actinic Keratoses

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (27)

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-Etienne, France

Kath. Klinikum Bochum St. Josef-Hospital

Bochum, Germany

MVZ Dermatologisches Zentrum Bonn GmbH

Bonn, Germany

Private practice Quist

Bretzenheim, Germany

Private Practice Kurzen

Freising, Germany

Dermatologikum Hamburg

Hamburg, Germany

...and 17 more locations

Outcomes

Primary Outcomes

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).

Time frame: at 4 weeks or Last Observation Carried Forward (LOCF)

Secondary Outcomes

Local Skin Reaction (LSR) total score

Time frame: at 2 weeks (first follow-up)

Local Skin Reaction (LSR) total score

Time frame: at 8 weeks (last follow up)

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

Time frame: at 2 weeks (first follow-up)

Local Skin Reaction (LSR) items alone

Time frame: at 4 weeks (second follow up)

Local Skin Reaction (LSR) items alone

Time frame: at 8 weeks (last follow up)

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.

Time frame: at 2 weeks (first follow-up)

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.

Time frame: at 4 weeks (second follow up)

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.

Time frame: at 8 weeks (last follow up)

Local reactions according to Common Terminology Criteria for Adverse Event (CTCAE) grade 3 or 4

Intensity grading of adverse events

Time frame: at 2 weeks (first follow-up)

Local reactions according to Common Terminology Criteria for Adverse Event (CTCAE) grade 3 or 4

Intensity grading of adverse events

Time frame: at 4 weeks (second follow up)

Local reactions according to Common Terminology Criteria for Adverse Event (CTCAE) grade 3 or 4

Intensity grading of adverse events

Time frame: at 8 weeks (last follow up)

Adverse Events reported by patients or noticed by investigator

Time frame: at 2, 4 and 8 weeks (first follow-up)

Drop outs due to Adverse Events (AE) related to local skin reaction

discontinuation rate

Time frame: at 2, 4 and 8 weeks (first follow-up)

Use of rescue treatment

Time frame: at 2 weeks (first follow-up)

Use of rescue treatment

Time frame: at 4 weeks (second follow up)

Use of rescue treatment

Time frame: at 8 weeks (last follow up)

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

Time frame: at 4 weeks (end of treatment) or at Patient Withdrawal

Treatment adherence

assessed by the participant using a self questionnaire

Time frame: at 4 weeks

Treatment adherence

assessed by the participant using a self questionnaire

Time frame: at optional visit (when applicable), up to 8 weeks

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