Back to resultsRisk of Squamous Cell Carcinoma on Skin Areas Treated With Ingenol Mebutate Gel, 0.015% and Imiquimod Cream, 5%
Primary Purpose
Actinic Keratosis (AK)
Status
Completed
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
Ingenol Mebutate Gel, 0.015%
Imiquimod Cream, 5%
Sponsored by
About this trial
This is an interventional treatment trial for Actinic Keratosis (AK)
Eligibility Criteria
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:
- Non-childbearing potential, or,
- 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)
Sites / Locations
- CHU Angers - Service de Dermatologie
- CHU Besançon - Hôpital Jean Minjoz
- HOPITAL AVICENNE - Service de Dermatologie
- CHRU de Brest - Hôpital Morvan - Service de Dermatologie
- CHU Albert Michallon - Service de Dermatologie, Pôle Pluridisciplinaire de Médecine
- Hôpital Claude Huriez - CHRU de Lille - Clinique de Dermatologie
- Hôpital de la Timone - Service de Dermatologie Vénérologie
- CHU de Nantes - Hôtel Dieu - Unité Fonctionnelle de Dermatologie Cancérologie
- HOPITAL DE L ARCHET II - Service de Dermatologie-Vénérologie
- Hôpital Caremeau
- HOPITAL COCHIN TARNIER - Service de Dermatologie
- Hôpital Saint Louis - Service de Dermatologie
- CHU BORDEAUX - Hôpital Haut-Lévêque
- CHU Poitiers - Service de Dermatologie
- C.H.U. de Saint-Etienne - Hôpital Nord
- Hôpital d'instruction des Armées Bégin - Clinique Dermatologique
- Hautarztpraxis Simon
- Hauttumorzentrum Bochum Universitätsklinikum der Ruhr-Universität-Bochum
- Praxis Streit Bucholz
- Dermatologisches Zentrum, Am Krankenhaus 1
- Klinikum Dortmund - Hautklinik
- Mensingderma
- Universitätsklinikum Leipzig Klinik für Dermatologie, Venerologie und Allergologie
- Hautpraxis Dr. Ina Schulze
- Hauttumorzentrum Münster
- Klinik für Dermatologie und Allergologie, Klinikum Vest, Behandlungszentrum, Knappschaftskrankenhaus Recklinghausen,
- Universitätklinikum Regensburg
- Praxis Dr. Hoffmann
- Praxis Derma Hübinger
- Universitätsklinikum Würzburg
- Ninewells Hospital
- Cumberland Infirmary
- Heavitree Hospital
- Brighton General Hospital
- Manchester Royal Infirmary
- Monklands Hospital
- Scunthorpe General Hospital
- Royal Gwent Hospital
- Harrogate District Hospital
- Scarborough Hospital
- Cannock Chase Hospital
- East Surrey Hospital
- Southlands Hospital
- St Luke's Hospital
- Chapel Allerton Hospital
- Hull Royal Infirmary
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Ingenol Mebutate
Imiquimod
Arm Description
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
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
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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)
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)
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01926496
Brief Title
Risk of Squamous Cell Carcinoma on Skin Areas Treated With Ingenol Mebutate Gel, 0.015% and Imiquimod Cream, 5%
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
Study Type
Interventional
2. Study Status
Record Verification Date
August 2020
Overall Recruitment Status
Completed
Study Start Date
September 11, 2013 (Actual)
Primary Completion Date
July 11, 2019 (Actual)
Study Completion Date
July 11, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
LEO Pharma
4. Oversight
Data Monitoring Committee
No
5. Study Description
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Actinic Keratosis (AK)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
485 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Ingenol Mebutate
Arm Type
Experimental
Arm Description
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
Arm Title
Imiquimod
Arm Type
Active Comparator
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Ingenol Mebutate Gel, 0.015%
Other Intervention Name(s)
Picato®
Intervention Description
Ingenol mebutate gel 0.015 % (Picato®) applied on the selected treatment area. Retreatment if the treatment field is not completely cleared of AKs.
Intervention Type
Drug
Intervention Name(s)
Imiquimod Cream, 5%
Other Intervention Name(s)
Aldara®
Intervention Description
Imiquimod 5% cream applied to the selected treatment area. Retreatment if the treatment field is not completely cleared of AKs
Primary Outcome Measure Information:
Title
Incidence of SCC
Description
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.
Time Frame
3 years
Secondary Outcome Measure Information:
Title
Incidence of SCC and Other Neoplasia
Description
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.
Time Frame
3 years
Title
Number of Participants With Complete Clearance of AK Lesions After Last Treatment
Description
To compare the complete clearance of AK lesions in the selected treatment area after the last treatment cycle (at Week 8 or 16)
Time Frame
8-16 weeks
Title
Number of Participants With Partial Clearance of AK Lesions
Description
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)
Time Frame
8-16 weeks
Title
Number of Participants With Complete Clearance of AK Lesions at 12 Months
Description
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.
Time Frame
1 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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:
Non-childbearing potential, or,
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rolf-Markus Szeimies, Prof.Dr.med.
Organizational Affiliation
Klinik für Dermatologie und Allergologie
Official's Role
Principal Investigator
Facility Information:
Facility Name
CHU Angers - Service de Dermatologie
City
Angers
ZIP/Postal Code
49933
Country
France
Facility Name
CHU Besançon - Hôpital Jean Minjoz
City
Besançon
ZIP/Postal Code
25030
Country
France
Facility Name
HOPITAL AVICENNE - Service de Dermatologie
City
Bobigny
ZIP/Postal Code
93009
Country
France
Facility Name
CHRU de Brest - Hôpital Morvan - Service de Dermatologie
City
Brest
ZIP/Postal Code
29609
Country
France
Facility Name
CHU Albert Michallon - Service de Dermatologie, Pôle Pluridisciplinaire de Médecine
City
Grenoble
ZIP/Postal Code
38043
Country
France
Facility Name
Hôpital Claude Huriez - CHRU de Lille - Clinique de Dermatologie
City
Lille
ZIP/Postal Code
59037
Country
France
Facility Name
Hôpital de la Timone - Service de Dermatologie Vénérologie
City
Marseille
ZIP/Postal Code
13385
Country
France
Facility Name
CHU de Nantes - Hôtel Dieu - Unité Fonctionnelle de Dermatologie Cancérologie
City
Nantes
ZIP/Postal Code
44093
Country
France
Facility Name
HOPITAL DE L ARCHET II - Service de Dermatologie-Vénérologie
City
Nice
ZIP/Postal Code
06202
Country
France
Facility Name
Hôpital Caremeau
City
Nimes
ZIP/Postal Code
30029
Country
France
Facility Name
HOPITAL COCHIN TARNIER - Service de Dermatologie
City
Paris
ZIP/Postal Code
75006
Country
France
Facility Name
Hôpital Saint Louis - Service de Dermatologie
City
Paris
ZIP/Postal Code
75475
Country
France
Facility Name
CHU BORDEAUX - Hôpital Haut-Lévêque
City
Pessac
ZIP/Postal Code
33604
Country
France
Facility Name
CHU Poitiers - Service de Dermatologie
City
Poitiers
ZIP/Postal Code
86021
Country
France
Facility Name
C.H.U. de Saint-Etienne - Hôpital Nord
City
Saint-Etienne
ZIP/Postal Code
42055
Country
France
Facility Name
Hôpital d'instruction des Armées Bégin - Clinique Dermatologique
City
St Mandé
ZIP/Postal Code
94160
Country
France
Facility Name
Hautarztpraxis Simon
City
Berlin
ZIP/Postal Code
10827
Country
Germany
Facility Name
Hauttumorzentrum Bochum Universitätsklinikum der Ruhr-Universität-Bochum
City
Bochum
ZIP/Postal Code
44791
Country
Germany
Facility Name
Praxis Streit Bucholz
City
Buchholz
ZIP/Postal Code
21244
Country
Germany
Facility Name
Dermatologisches Zentrum, Am Krankenhaus 1
City
Buxtehude
ZIP/Postal Code
21614
Country
Germany
Facility Name
Klinikum Dortmund - Hautklinik
City
Dortmund
ZIP/Postal Code
44137
Country
Germany
Facility Name
Mensingderma
City
Hamburg
ZIP/Postal Code
22391
Country
Germany
Facility Name
Universitätsklinikum Leipzig Klinik für Dermatologie, Venerologie und Allergologie
City
Leipzig
ZIP/Postal Code
04103
Country
Germany
Facility Name
Hautpraxis Dr. Ina Schulze
City
Markkleeberg
ZIP/Postal Code
04416
Country
Germany
Facility Name
Hauttumorzentrum Münster
City
Münster
ZIP/Postal Code
48149
Country
Germany
Facility Name
Klinik für Dermatologie und Allergologie, Klinikum Vest, Behandlungszentrum, Knappschaftskrankenhaus Recklinghausen,
City
Recklinghausen
ZIP/Postal Code
45657
Country
Germany
Facility Name
Universitätklinikum Regensburg
City
Regensburg
ZIP/Postal Code
93053
Country
Germany
Facility Name
Praxis Dr. Hoffmann
City
Witten
ZIP/Postal Code
58453
Country
Germany
Facility Name
Praxis Derma Hübinger
City
Wuppertal
ZIP/Postal Code
42105
Country
Germany
Facility Name
Universitätsklinikum Würzburg
City
Würzburg
ZIP/Postal Code
97080
Country
Germany
Facility Name
Ninewells Hospital
City
Dundee
State/Province
Angus
Country
United Kingdom
Facility Name
Cumberland Infirmary
City
Carlisle
State/Province
Cumbria
Country
United Kingdom
Facility Name
Heavitree Hospital
City
Exeter
State/Province
Devon
Country
United Kingdom
Facility Name
Brighton General Hospital
City
Brighton
State/Province
East Sussex
Country
United Kingdom
Facility Name
Manchester Royal Infirmary
City
Manchester
State/Province
Greater Manchester
Country
United Kingdom
Facility Name
Monklands Hospital
City
Airdrie
State/Province
Lanarkshire
Country
United Kingdom
Facility Name
Scunthorpe General Hospital
City
Scunthorpe
State/Province
Lincolnshire
Country
United Kingdom
Facility Name
Royal Gwent Hospital
City
Newport
State/Province
Monmouthshire
Country
United Kingdom
Facility Name
Harrogate District Hospital
City
Harrogate
State/Province
North Yorkshire
Country
United Kingdom
Facility Name
Scarborough Hospital
City
Scarborough
State/Province
North Yorkshire
Country
United Kingdom
Facility Name
Cannock Chase Hospital
City
Cannock
State/Province
Staffordshire
Country
United Kingdom
Facility Name
East Surrey Hospital
City
Redhill
State/Province
Surrey
Country
United Kingdom
Facility Name
Southlands Hospital
City
Shoreham-by-Sea
State/Province
West Sussex
Country
United Kingdom
Facility Name
St Luke's Hospital
City
Bradford
State/Province
West Yorkshire
Country
United Kingdom
Facility Name
Chapel Allerton Hospital
City
Leeds
State/Province
West Yorkshire
Country
United Kingdom
Facility Name
Hull Royal Infirmary
City
Hull
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
Risk of Squamous Cell Carcinoma on Skin Areas Treated With Ingenol Mebutate Gel, 0.015% and Imiquimod Cream, 5%
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