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

Actinic Keratosis (AK) Clinical Trial

Official title:

A Phase 4 Trial Comparing the Cumulative Incidence of SCC After Treatment With Ingenol Mebutate and Imiquimod for Multiple Actinic Keratoses on Face and Scalp. A Multi-centre, Randomised, Two-arm, Open Label, Active-controlled, Parallel Group, 36-month Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01926496
• Other study ID #: LP0041-63
• Secondary ID: 2012-003112-31
• Status: Completed
• Phase: Phase 4
• Start date: September 11, 2013
• Est. completion date: July 11, 2019

Study information

• Verified date: August 2020
• Source: LEO Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 485
• Est. completion date: July 11, 2019
• Est. primary completion date: July 11, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Signed Informed Consent Form (ICF) prior to any trial-related procedures

2. Subjects with 5 to 9 clinically typical, visible and discrete AKs within a contiguous 25 cm² treatment area on the face or scalp.

3. Subject at least 18 years of age

4. Female subjects must be of either:

1. Non-childbearing potential, or,

2. Childbearing potential, provided there is a confirmed negative urine pregnancy test

5. Female subjects of childbearing potential must be willing to use highly effective methods of contraception (Pearl index < 1%)

Exclusion Criteria:

1. 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

2. Selected treatment area lesions that have atypical clinical appearance (e.g., hypertrophic, hyperkeratotic or cutaneous horn).

3. History of SCC, BCC, malignant melanoma or other neoplasia in the selected treatment area.

4. 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

5. 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)

6. Organ transplant recipients

7. Immunosuppressed subjects (for example HIV patients)

8. Female subjects who are breastfeeding.

9. Subjects who are institutionalised by court order or by the local authority

10. 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)

Related Conditions & MeSH terms

• Actinic Keratosis (AK)
• Keratosis
• Keratosis, Actinic

Intervention

Drug:
• Ingenol Mebutate Gel, 0.015%
Ingenol mebutate gel 0.015 % (Picato®) applied on the selected treatment area. Retreatment if the treatment field is not completely cleared of AKs.
• Imiquimod Cream, 5%
Imiquimod 5% cream applied to the selected treatment area. Retreatment if the treatment field is not completely cleared of AKs

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
LEO Pharma

Countries where clinical trial is conducted

France,  Germany,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of SCC	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.	3 years
Secondary	Incidence of SCC and Other Neoplasia	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.	3 years
Secondary	Number of Participants With Complete Clearance of AK Lesions After Last Treatment	To compare the complete clearance of AK lesions in the selected treatment area after the last treatment cycle (at Week 8 or 16)	8-16 weeks
Secondary	Number of Participants With Partial Clearance of AK Lesions	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)	8-16 weeks
Secondary	Number of Participants With Complete Clearance of AK Lesions at 12 Months	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.	1 year