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

NCT04875026 | Completed Phase 4 FDA Drug FDA Device

• 2 other identifiers: W00118 CR 4012020-000851-11
• Study Type: interventional
• Target: 146
• Locations: 4 countries
• Sites: 27

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.

Conditions

Actinic Keratoses

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (29)

• Local Skin Reaction (LSR) total score

  at 2 weeks (first follow-up)

• Local Skin Reaction (LSR) total score

  at 8 weeks (last follow up)

• Local Skin Reaction (LSR) items alone

  at 2 weeks (first follow-up)

• Local Skin Reaction (LSR) items alone

  at 4 weeks (second follow up)

• Local Skin Reaction (LSR) items alone

  at 8 weeks (last follow up)

Study Arms (2)

5-fluorouracil 4% (Tolak) + Dexeryl

EXPERIMENTAL

This group will apply 5-FU once daily for 4 weeks, and Dexeryl once daily for 8 weeks.

Drug: 5-fluorouracil 4% (Tolak); Device: Dexeryl

5-fluorouracil 4% (Tolak)

OTHER

This group will only apply 5-FU once daily for 4 weeks.

Drug: 5-fluorouracil 4% (Tolak)

Interventions

5-fluorouracil 4% (Tolak) DRUG

Application of Tolak once daily in the evening for 4 weeks

5-fluorouracil 4% (Tolak); 5-fluorouracil 4% (Tolak) + Dexeryl

Dexeryl DEVICE

Application of Dexeryl once daily in the morning for 8 weeks

5-fluorouracil 4% (Tolak) + Dexeryl

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants are eligible only if all of the following criteria apply:
• Age
• Participant must be more than 18 years old inclusive, at the time of signing the informed consent.
• Type of Participant and Disease Characteristics
• Individuals with a clinical diagnosis of actinic keratosis (AK).
• 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.
• 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
• 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
• 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
• Affiliated to a social security system, or is a beneficiary (if applicable in the national regulation).

You may not qualify if:

• Participants are excluded from the study if any of the following criteria apply:
• Medical Conditions
• With AK lesions within treatment areas which are hyperkeratotic or which are clinically suspected to be squamous cell carcinoma (SCC).
• With pre-existing local skin reactions with a total score ≥ 3.
• History of hypersensitivity to the ingredients of Tolak® or Dexeryl®.
• With a known allergy to peanut or soya.
• Non postmenopausal or non surgically sterile woman considered as WOCBP, pregnant or breastfeeding women.
• Prior/Concomitant Therapy
• Under systemic 5-fluorouracil or any systemic cancer treatment within eight weeks prior to the study.
• 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.
• Treated with systemic steroids, immunosuppressants or immunomodulators within four weeks prior to the study.
• Under prescription retinoids or topical steroids in the treatment area(s) within four weeks prior to the study.
• With known dihydropyrimidinedehydrogénase (DPD) deficiency or under treatment with brivudine, sorivudine or analogues within 4 weeks prior to starting the study.
• Treated with glycolic acid products and alpha-hydroxy products in the treatment area(s) within four weeks prior to starting the study.
• Treated with chemical peeling products in the treatment area(s) within eight weeks prior to starting the study.

Sponsors & Collaborators

• Pierre Fabre Medicament: lead
• Clinact: collaborator

Study Sites (27)

Private practice Maire

Arras, France

Location

Chu de Nantes Hôtel-Dieu

Nantes, France

Location

CHU Pau

Pau, France

Location

CHU Poitiers

Poitiers, France

Location

CHU St Etienne Hopital Nord

Saint-Etienne, France

Location

Kath. Klinikum Bochum St. Josef-Hospital

Bochum, Germany

Location

MVZ Dermatologisches Zentrum Bonn GmbH

Bonn, Germany

Location

Private practice Quist

Bretzenheim, Germany

Location

Private Practice Kurzen

Freising, Germany

Location

Dermatologikum Hamburg

Hamburg, Germany

Location

Hautarztpraxis

Witten, 58453, Germany

Location

CentroDerm Clinic

Witten, Germany

Location

Uni Clinic Brescia

Brescia, Italy

Location

Uni Clinic Catania

Catania, Italy

Location

Uni Clinic L'Aquila

Coppito, Italy

Location

Policlinico San Martino

Genova, Italy

Location

University of Messina

Messina, Italy

Location

Uni Clinic Modena

Modena, Italy

Location

NAPLES VANVITELLI UNIVERSITI (Federico II Hospital)

Napoli, Italy

Location

Azienda Unità Sanitaria Locale - IRCCS

Reggio Emilia, Italy

Location

Catholic University Fondazione Policlinico Universitario A. Gemelli

Roma, Italy

Location

Sapienza University of Rome - Polo Pontino

Terracina, Italy

Location

Centre medic Congres

Barcelona, Spain

Location

Hospital Alfredo Espinosa

Bilbao, Spain

Location

Hospital Universitario Infanta Leonor

Madrid, Spain

Location

Instituto Valenciano de Oncología,

Valencia, Spain

Location

Hospital Marina Baixa

Villajoyosa, Spain

Location

MeSH Terms

Conditions

Keratosis, Actinic

Interventions

Fluorouracil

Condition Hierarchy (Ancestors)

Precancerous Conditions; Neoplasms; Keratosis; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Eggert STOCKFLETH, Pr.

  Kath. Klinikum Bochum St. Josef-Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Masking Details: This study is investigator-blinded
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2021
• First Posted: May 6, 2021
• Study Start: February 16, 2021
• Primary Completion: January 31, 2022
• Study Completion: January 31, 2022
• Last Updated: September 19, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

FR (5); DE (7); IT (10); ES (5)