Imiquimod Versus Photodynamic Therapy of Actinic Keratoses in Organ Transplant Recipients - Full Text View

Purpose

The purpose of this study is to compare two different therapies for actinic keratoses in organ transplant recipients with regard to efficacy and tolerability. The investiagtors are planning to examine treatment with Imiquimod 5% cream versus treatment with Methyl-aminolaevulinate 16% cream and subsequent irradiation with red light, so-called photodynamic therapy, in this patients' group. A secondary objective of our study is to investigate the reduction in the field cancerisation after both treatments using fluorescence diagnostic method and digital imaging.

Condition	Intervention	Phase
Actinic Keratoses	Other: photodynamic therapy Drug: imiquimod 5% cream	Phase 4

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Topical Imiquimod 5% Cream Therapy Versus Photodynamic Therapy With Methyl-aminolaevulinate 16% Cream of Actinic Keratoses in Organ Transplant Recipients

Resource links provided by NLM:

Drug Information available for: Aminolevulinic acid Aminolevulinic acid hydrochloride Methyl aminolevulinate Imiquimod

U.S. FDA Resources

Further study details as provided by Medical University of Vienna:

Primary Outcome Measures:

Clinical complete response rate of actinic keratoses [ Time Frame: 4 weeks after end of treatment ] [ Designated as safety issue: No ]
The clinical complete response rate of actinic keratoses is defined as a proportion of the number of actinic keratoses with a clinically determined complete clearance(no visible and/or palpable actinic keratoses) to the number of the actinic keratoses at baseline.

Secondary Outcome Measures:

clinical complete response rate of actinic keratoses [ Time Frame: 6 and 12 months after end of treatment ] [ Designated as safety issue: No ]
The clinical complete response rate of actinic keratoses is defined as a proportion of the number of actinic keratoses with a clinically determined complete clearance(no visible and/or palpable actinic keratoses) to the number of the actinic keratoses at baseline.
global reduction in the area of specific fluorescence [ Time Frame: 1, 6 and 12 months after end of treatment ] [ Designated as safety issue: No ]
Prior to photodynamic therapy an illumination of the treated area with a Wood light will be prepared (fluorescence diagnostik). The specific fluorescence will be detected and documented using the non-invasive fluorescence-imaging system Dyaderm, Biocam, Germany.
global patient's satisfaction [ Time Frame: 3, 6 and 12 months after end of treatment ] [ Designated as safety issue: Yes ]
The global patient's satisfaction will be determined by the patients themselves on a 10 cm visual analog scale. 0 means extremely unsatisfied, 1-3 means unsatisfied, 5-7 means moderately satisfied, 8-10 means highly satisfied.

Estimated Enrollment:	34
Study Start Date:	September 2012
Estimated Study Completion Date:	September 2014
Estimated Primary Completion Date:	September 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: photodynamic therapy Methyl-aminolaevulinate 16% cream (Metvix 160mg/g cream) will be applied 1 mm thick on the treated area, which has a maximal diameter of 8 cm2, and will be covered with a semipermeable dressing (Suprasorb F, Lohmann & Rauscher, Vienna, Austria)for 3 hours. Afterwards the cream leftovers will be removed by 0.9% NaCl solution. Following the treated area will be irradiated with heat-free visible red light at a peak wavelength of 630 nm with a single dose of 37 J/cm2 (Actilite model: CL128, PhotoCure, Norway). This treatment will be repeated in two weeks.	Other: photodynamic therapy Methyl-aminolaevulinate 16% cream (Metvix) will be applied on the treated area under occlusion for 3 hours. It follows irradiation with visible red light at a peak wavelength of 630 nm (Actilite CL128) with a single dose of 37 J/cm2. Other Name: Metvix 160mg/g cream photodynamic therapy
Active Comparator: imiquimod 5% cream 250 mg imiquimod 5% cream (Aldara 5% cream) will be applied over night, for a total of 3 nights in a week, for duration of 4 weeks.	Drug: imiquimod 5% cream 250 mg imiquimod 5% cream will be applied over night for a total of 3 nights in the week, for duration of 4 weeks Other Name: Aldara 5% cream

Arms

Assigned Interventions

Experimental: photodynamic therapy

Methyl-aminolaevulinate 16% cream (Metvix 160mg/g cream) will be applied 1 mm thick on the treated area, which has a maximal diameter of 8 cm2, and will be covered with a semipermeable dressing (Suprasorb F, Lohmann & Rauscher, Vienna, Austria)for 3 hours. Afterwards the cream leftovers will be removed by 0.9% NaCl solution. Following the treated area will be irradiated with heat-free visible red light at a peak wavelength of 630 nm with a single dose of 37 J/cm2 (Actilite model: CL128, PhotoCure, Norway). This treatment will be repeated in two weeks.

Other: photodynamic therapy

Methyl-aminolaevulinate 16% cream (Metvix) will be applied on the treated area under occlusion for 3 hours. It follows irradiation with visible red light at a peak wavelength of 630 nm (Actilite CL128) with a single dose of 37 J/cm2.

Other Name: Metvix 160mg/g cream photodynamic therapy

Active Comparator: imiquimod 5% cream

250 mg imiquimod 5% cream (Aldara 5% cream) will be applied over night, for a total of 3 nights in a week, for duration of 4 weeks.

Drug: imiquimod 5% cream

250 mg imiquimod 5% cream will be applied over night for a total of 3 nights in the week, for duration of 4 weeks

Other Name: Aldara 5% cream

Detailed Description:

Organ transplant patients (OTP) require lifelong immunosuppressive therapy and consequently are prone to develop skin tumors, i.e skin cancer is the most frequent malignancy in organ transplant recipients. OTP frequently develop extensive areas of actinic damage, epidermal dysplasia, wich accounts for increased risk of aggressive skin cancer development in susceptible patients, and are referred to as "field cancerisation". Therefore the whole area of field cancerisation has to be treated. In our study we will treat this areas with two different methods and not only the single visible lesions of actinic keratoses.In this open prospective randomized intraindividual study one half of the patients' scalp or face will be treated with Imiquimod 5% cream for 4 weeks, 3 times a week, and the other half with Methyl-aminolaevulinate 16% cream photodynamic therapy, two applications in two weeks interval. The pre- and post treatment extension of field cancerisation will be assessed by means of a highly sensitive digital fluorescence imaging system.

Eligibility

Ages Eligible for Study:	18 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Age 18 years or older
Patients who had received a kidney, liver, lung or heart transplant more than 3 years prior to inclusion into the study
Patients who had been treated at least 6 months prior to study entry with a stable twofold or threefold immunosuppressive treatment
Patients who had clinically confirmed epithelial dysplasia (actinic keratoses) in at least two anatomically separated contralateral areas on the face and/or scalp with comparable size and extension and minimum distance of 5 cm

Exclusion Criteria:

Invasive squamous cell carcinoma or basal cell carcinoma in the treatment area
Known allergy to imiquimod and/or methyl-aminolaevulinate and/or one of the other components of the investigational products and/or peanut oil
Patients who have received retinoids, interferons or investigational drugs within 4 weeks of study initiation
Patients who are participating in othe dermatological study
Persistent Hepatitis B or C infections
Any evidence of systemic cancer
Patients who have received any systemic cancer chemotherapy or radiation therapy
Pregnant or lactating women
Patients

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01538901

Contacts

Contact: Stanislava Tzaneva, Doz. Dr.	0043140400 ext 7700	stanislava.tzaneva@meduniwien.ac.at
Contact: Alexandra Geusau, Prof. Dr.	0043140400 ext 7705	alexandra.geusau@meduniwien.ac.at

Locations

Austria
Medical University of Vienna, University Clinic of Dermatology	Not yet recruiting
Vienna, Austria, 1090
Contact: Stanislava Tzaneva, Doz. Dr. +43140400 ext 7700 stanislava.tzaneva@meduniwien.ac.at
Contact: Alexandra Geusau, Prof. Dr. +43140400 ext 7705 alexandra.geusau@meduniwien.ac.at
Principal Investigator: Alexandra Geusau, Prof. Dr.
Principal Investigator: Stanislava Tzaneva, Doz. Dr.
Medical University of Vienna	Recruiting
Vienna, Austria, 1090
Contact: Stanislava Tzaneva, MD +431404007702 stanislava.tzaneva@meduniwien.ac.at
Contact: Alexandra Geusau, MD +431404007703 alexandra.geusau@meduniwien.ac.at
Principal Investigator: Stanislava Tzaneva, MD

Sponsors and Collaborators

Medical University of Vienna

Investigators

Principal Investigator:	Stanislava Tzaneva, Doz. Dr.	Medical University of Vienna, University Clinic of Dermatology, Division of General Dermatology
Principal Investigator:	Alexandra Geusau, Prof. Dr.	Medical University of Vienna, Division of Immunology, Allergy and Infectious Diseases

More Information

Publications:

Ulrich C, Bichel J, Euvrard S, Guidi B, Proby CM, van de Kerkhof PC, Amerio P, Rønnevig J, Slade HB, Stockfleth E. Topical immunomodulation under systemic immunosuppression: results of a multicentre, randomized, placebo-controlled safety and efficacy study of imiquimod 5% cream for the treatment of actinic keratoses in kidney, heart, and liver transplant patients. Br J Dermatol. 2007 Dec;157 Suppl 2:25-31.

Dragieva G, Prinz BM, Hafner J, Dummer R, Burg G, Binswanger U, Kempf W. A randomized controlled clinical trial of topical photodynamic therapy with methyl aminolaevulinate in the treatment of actinic keratoses in transplant recipients. Br J Dermatol. 2004 Jul;151(1):196-200.

Stockfleth E, Ulrich C, Meyer T, Christophers E. Epithelial malignancies in organ transplant patients: clinical presentation and new methods of treatment. Recent Results Cancer Res. 2002;160:251-8.

Stern RS, Bolshakov S, Nataraj AJ, Ananthaswamy HN. p53 mutation in nonmelanoma skin cancers occurring in psoralen ultraviolet a-treated patients: evidence for heterogeneity and field cancerization. J Invest Dermatol. 2002 Aug;119(2):522-6.

Geusau A, Dunkler D, Messeritsch E, Sandor N, Heidler G, Rödler S, Ankersmit J, Zuckermann A, Tschachler E. Non-melanoma skin cancer and its risk factors in an Austrian population of heart transplant recipients receiving induction therapy. Int J Dermatol. 2008 Sep;47(9):918-25.

Fernández-Guarino M, Harto A, Sánchez-Ronco M, Pérez-García B, Marquet A, Jaén P. [Retrospective, descriptive, observational study of treatment of multiple actinic keratoses with topical methyl aminolevulinate and red light: results in clinical practice and correlation with fluorescence imaging]. Actas Dermosifiliogr. 2008 Dec;99(10):779-87. Spanish.

Responsible Party:	Stanislava Tzaneva, Doz. Dr., Medical University of Vienna
ClinicalTrials.gov Identifier:	NCT01538901 History of Changes
Other Study ID Numbers:	IPDTAKOTR/V06/28.12.11
Study First Received:	February 19, 2012
Last Updated:	September 6, 2012
Health Authority:	Austria: Austrian Agency for Health and Food Safety (AGES)

Keywords provided by Medical University of Vienna:

actinic keratoses
organ transplant recipients
photodynamic therapy
imiquimod

Additional relevant MeSH terms:

Keratosis
Keratosis, Actinic
Skin Diseases
Precancerous Conditions
Neoplasms
Aminolevulinic Acid
Methyl 5-aminolevulinate
Imiquimod
Photosensitizing Agents

Radiation-Sensitizing Agents
Physiological Effects of Drugs
Pharmacologic Actions
Dermatologic Agents
Therapeutic Uses
Adjuvants, Immunologic
Immunologic Factors
Antineoplastic Agents
Interferon Inducers

ClinicalTrials.gov processed this record on May 23, 2013

Imiquimod Versus Photodynamic Therapy of Actinic Keratoses in Organ Transplant Recipients (AKtransplant)