Risk of Squamous Cell Carcinoma on Skin Areas Treated With Ingenol Mebutate Gel, 0.015% and Imiquimod Cream, 5%

Phase 4

Completed

Conditions: Actinic Keratosis (AK)

Interventions: Drug: Imiquimod Cream, 5%
Drug: Ingenol Mebutate Gel, 0.015%

Registration Number: NCT01926496

Lead Sponsor: LEO Pharma

Brief Summary: The purpose of the study is to compare the risk of developing squamous skin cancer (SCC) or other types of cancer after treatment of AKs with ingenol mebutate gel or imiquimod cream. Subjects will be randomised to treatment with ingenol mebutate or imiquimod and will receive a second treatment cycle with the same treatment if the first treatment does not clear all AKs. Subjects will be followed over a period of three year (36 months) after first treatment

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 485

Inclusion Criteria

Signed Informed Consent Form (ICF) prior to any trial-related procedures
Subjects with 5 to 9 clinically typical, visible and discrete AKs within a contiguous 25 cm² treatment area on the face or scalp.
Subject at least 18 years of age
Female subjects must be of either:
1. Non-childbearing potential, or,
2. Childbearing potential, provided there is a confirmed negative urine pregnancy test
Female subjects of childbearing potential must be willing to use highly effective methods of contraception (Pearl index < 1%)

Exclusion Criteria

Location of the selected treatment area:
- on the periorbital skin
- on the perioral skin/around the nostrils
- within 5 cm of an incompletely healed wound
- within 10 cm of a suspected BCC or SCC or other neoplasia
Selected treatment area lesions that have atypical clinical appearance (e.g., hypertrophic, hyperkeratotic or cutaneous horn).
History of SCC, BCC, malignant melanoma or other neoplasia in the selected treatment area.
History or evidence of skin conditions other than the trial indication that would interfere with evaluation of the trial medication in the selected treatment area
Use of ingenol mebutate and/or imiquimod in and within 5 cm of the selected treatment area within 2 years prior to Screening (Visit 1)
Organ transplant recipients
Immunosuppressed subjects (for example HIV patients)
Female subjects who are breastfeeding.
Subjects who are institutionalised by court order or by the local authority
In the opinion of the investigator, the subject is unlikely to comply with the Clinical Study Protocol (e.g. alcoholism, drug dependency or psychotic state)

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Imiquimod	Imiquimod Cream, 5%	Arm B: Imiquimod 5% cream applied 3 days per week for 4 weeks to the selected treatment area followed by 4 weeks' rest. Retreatment for another 4 weeks if the treatment field is not completely cleared of AKs at Week 8
Ingenol Mebutate	Ingenol Mebutate Gel, 0.015%	Arm A: Ingenol mebutate gel 0.015% applied daily for 3 consecutive days to the selected treatment area followed by 8 weeks' rest. Retreatment for another 3 consecutive days if the treatment field is not completely cleared of AKs at Week 8

Primary Outcome Measures

Name	Time	Method
Incidence of SCC	3 years	Cumulative incidence of SCC after treatment with ingenol mebutate gel and imiquimod cream.\> The primary response criterion is diagnosis of SCC (defined as invasive SCC i.e. excludes SCC in situ) in the treatment field across the 3-year trial period.\> Kaplan-Meier estimate based on time to SCC or censoring.

Secondary Outcome Measures

Name	Time	Method
Incidence of SCC and Other Neoplasia	3 years	Cumulative incidence of SCC and other neoplasia after treatment with ingenol mebutate gel and imiquimod cream.\> The secondary response criterion is diagnosis of SCC and other neoplasia in the treatment field across the 3-year trial period.\> Kaplan-Meier estimate based on time to SCC and other neoplasia, or censoring.
Number of Participants With Partial Clearance of AK Lesions	8-16 weeks	To compare the partial (at least 75%) clearance of AK lesions in the selected treatment area after the last treatment cycle (at Week 8 or 16)
Number of Participants With Complete Clearance of AK Lesions After Last Treatment	8-16 weeks	To compare the complete clearance of AK lesions in the selected treatment area after the last treatment cycle (at Week 8 or 16)
Number of Participants With Complete Clearance of AK Lesions at 12 Months	1 year	To compare the complete clearance of AK lesions at 12 months, defined as no AK lesions in the selected treatment area at any time from the last treatment cycle at Week 8 or 16 through to Month 12.

Trial Locations

Locations (46): Ninewells Hospital
🇬🇧
Dundee, Angus, United Kingdom
Scunthorpe General Hospital
🇬🇧
Scunthorpe, Lincolnshire, United Kingdom
East Surrey Hospital
🇬🇧
Redhill, Surrey, United Kingdom
HOPITAL AVICENNE - Service de Dermatologie
🇫🇷
Bobigny, France
Manchester Royal Infirmary
🇬🇧
Manchester, Greater Manchester, United Kingdom
Hôpital Saint Louis - Service de Dermatologie
🇫🇷
Paris, France
HOPITAL DE L ARCHET II - Service de Dermatologie-Vénérologie
🇫🇷
Nice, France
Universitätsklinikum Leipzig Klinik für Dermatologie, Venerologie und Allergologie
🇩🇪
Leipzig, Germany
CHU de Nantes - Hôtel Dieu - Unité Fonctionnelle de Dermatologie Cancérologie
🇫🇷
Nantes, France
Hautarztpraxis Simon
🇩🇪
Berlin, Germany
Brighton General Hospital
🇬🇧
Brighton, East Sussex, United Kingdom
Hull Royal Infirmary
🇬🇧
Hull, United Kingdom
HOPITAL COCHIN TARNIER - Service de Dermatologie
🇫🇷
Paris, France
Praxis Streit Bucholz
🇩🇪
Buchholz, Germany
Hautpraxis Dr. Ina Schulze
🇩🇪
Markkleeberg, Germany
Chapel Allerton Hospital
🇬🇧
Leeds, West Yorkshire, United Kingdom
Mensingderma
🇩🇪
Hamburg, Germany
Hôpital Caremeau
🇫🇷
Nimes, France
CHU BORDEAUX - Hôpital Haut-Lévêque
🇫🇷
Pessac, France
C.H.U. de Saint-Etienne - Hôpital Nord
🇫🇷
Saint-Etienne, France
Praxis Derma Hübinger
🇩🇪
Wuppertal, Germany
Monklands Hospital
🇬🇧
Airdrie, Lanarkshire, United Kingdom
Hauttumorzentrum Münster
🇩🇪
Münster, Germany
Southlands Hospital
🇬🇧
Shoreham-by-Sea, West Sussex, United Kingdom
St Luke's Hospital
🇬🇧
Bradford, West Yorkshire, United Kingdom
Heavitree Hospital
🇬🇧
Exeter, Devon, United Kingdom
Harrogate District Hospital
🇬🇧
Harrogate, North Yorkshire, United Kingdom
Royal Gwent Hospital
🇬🇧
Newport, Monmouthshire, United Kingdom
Scarborough Hospital
🇬🇧
Scarborough, North Yorkshire, United Kingdom
CHU Poitiers - Service de Dermatologie
🇫🇷
Poitiers, France
Klinikum Dortmund - Hautklinik
🇩🇪
Dortmund, Germany
Klinik für Dermatologie und Allergologie, Klinikum Vest, Behandlungszentrum, Knappschaftskrankenhaus Recklinghausen,
🇩🇪
Recklinghausen, Germany
CHU Angers - Service de Dermatologie
🇫🇷
Angers, France
CHU Besançon - Hôpital Jean Minjoz
🇫🇷
Besançon, France
CHRU de Brest - Hôpital Morvan - Service de Dermatologie
🇫🇷
Brest, France
CHU Albert Michallon - Service de Dermatologie, Pôle Pluridisciplinaire de Médecine
🇫🇷
Grenoble, France
Hôpital Claude Huriez - CHRU de Lille - Clinique de Dermatologie
🇫🇷
Lille, France
Hôpital de la Timone - Service de Dermatologie Vénérologie
🇫🇷
Marseille, France
Hôpital d'instruction des Armées Bégin - Clinique Dermatologique
🇫🇷
St Mandé, France
Hauttumorzentrum Bochum Universitätsklinikum der Ruhr-Universität-Bochum
🇩🇪
Bochum, Germany
Dermatologisches Zentrum, Am Krankenhaus 1
🇩🇪
Buxtehude, Germany
Praxis Dr. Hoffmann
🇩🇪
Witten, Germany
Universitätklinikum Regensburg
🇩🇪
Regensburg, Germany
Universitätsklinikum Würzburg
🇩🇪
Würzburg, Germany
Cumberland Infirmary
🇬🇧
Carlisle, Cumbria, United Kingdom
Cannock Chase Hospital
🇬🇧
Cannock, Staffordshire, United Kingdom