Prevention of Skin Cancer in High Risk Patients After Conversion to a Sirolimus-Based Immunosuppressive Protocol - Full Text View

Sponsored by:	Charite University, Berlin, Germany
Information provided by:	Charite University, Berlin, Germany
ClinicalTrials.gov Identifier:	NCT00866684

Purpose

Transplant recipients have a high risk to develop skin malignancies. This effect depends on the one hand on the immunosuppressive drugs themselves (i.e., azathioprine) and relates on the other hand on the dosage (i.e., calcineurin-inhibitors). Based on the encouraging results of previous, retrospective studies on patients treated with Sirolimus (SRL), these patients should be switched to an immunosuppressive regime including SRL, decreasing the dosage of calcineurin-inhibitors or converting from former immunosuppression. A conversion to a SRL-based therapy is effective in immunosuppression and safe regarding graft and patient survival.

This study was designed to assess whether a switch to a SRL-immunosuppressive therapy decreases the incidence/reoccurrence of skin neoplasm.

Condition	Intervention	Phase
Kidney Transplantation Skin Cancer	Drug: Sirolimus Drug: Azathioprine Drug: Mycophenolate Drug: Ciclosporin Drug: Tacrolimus	Phase IV

Study Type:	Interventional
Study Design:	Prevention, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	Prevention of Skin Cancer in High Risk Patients After Conversion to a Sirolimus-Based Immunosuppressive Protocol

Resource links provided by NLM:

MedlinePlus related topics: Cancer Kidney Transplantation Skin Cancer

Drug Information available for: Sirolimus Azathioprine sodium salt Cyclosporine Cyclosporin Tacrolimus anhydrous Tacrolimus Azathioprine

U.S. FDA Resources

Further study details as provided by Charite University, Berlin, Germany:

Primary Outcome Measures:

Progression of actinic keratosis I and II to III or invasive squamous cell carcinoma (SCC) or incidence/reoccurrence of neoplastic skin tumors [ Designated as safety issue: No ]

Secondary Outcome Measures:

Patient and graft survival rates, Incidence of non-cutaneous cancers and of selected AEs, Development of renal function, Renal biopsy changes, Development of proteinuria after conversation to SRL, Incidence and development of actinic keratosis I and II [ Designated as safety issue: Yes ]

Estimated Enrollment:	280
Study Start Date:	January 2007
Estimated Study Completion Date:	July 2011
Estimated Primary Completion Date:	January 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Patients will receive Sirolimus in addition to their previous immunosuppressive therapy.	Drug: Sirolimus Dosage form: coated tablet; Dosage: 4-8 micrograms/litre; Route of administration: oral use; Frequency: one tablet per day; Duration: 24 month
2: Active Comparator Patients will stay on their previous immunosuppressive regimen.	Drug: Azathioprine Dosage form: Coated tablet; dosage: 1-4 milligrams/kilogram; Frequency: daily; Duration: 24 month Drug: Mycophenolate Dosage form: Tablet; dosage: 2 gram; Frequency: daily; Duration: 24 month Drug: Ciclosporin Dosage form: Capsule; Dosage: 50-80 micrograms/litre; Frequency: daily; Duration: 24 month Drug: Tacrolimus Dosage form: Capsule; dosage: 3-5 micrograms/litre; Frequency: daily; Duration: 24 month

Arms

Assigned Interventions

1: Experimental

Patients will receive Sirolimus in addition to their previous immunosuppressive therapy.

Drug: Sirolimus

Dosage form: coated tablet; Dosage: 4-8 micrograms/litre; Route of administration: oral use; Frequency: one tablet per day; Duration: 24 month

2: Active Comparator

Patients will stay on their previous immunosuppressive regimen.

Drug: Azathioprine

Dosage form: Coated tablet; dosage: 1-4 milligrams/kilogram; Frequency: daily; Duration: 24 month

Drug: Mycophenolate

Dosage form: Tablet; dosage: 2 gram; Frequency: daily; Duration: 24 month

Drug: Ciclosporin

Dosage form: Capsule; Dosage: 50-80 micrograms/litre; Frequency: daily; Duration: 24 month

Drug: Tacrolimus

Dosage form: Capsule; dosage: 3-5 micrograms/litre; Frequency: daily; Duration: 24 month

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Recipients of renal allograft with current actinic keratosis I or II or successfully treated actinic keratosis III (inclusion possible immediately after completed wound healing from surgical excision), invasive squamous cell carcinoma (SCC), basal cell carcinoma and/or premalignant neoplastic skin lesions
Age 18 years and older
Minimum period of 6 month after renal transplantation
Stable renal function and a calculated creatinine clearance of at least 40 ml/min
Written informed consent
Proteinuria ≤ 800 mg/d at time of enrolment
Successfully treated solid tumor (no recurrence or metastasis in the last 2 years)

Exclusion Criteria:

Current Sirolimus- or Everolimus- intake
Instable graft function (creatinine clearance < 40 ml/min)
Graft rejection within the 3 previous months
Proteinuria > 800 mg/d
Non-controlled hyperlipidemia (Cholesterol >7,8 mmol/l, Triglycerides > 4)
Leucopenia < 2500/nl
Thrombocytopenia < 90/nl
Pregnancy or breastfeeding
Women of childbearing age without highly effective contraception (= defined as those which result in a low failure rate (i.e. less than 1 % per year))
Known allergy to macrolides
Current participation in other studies
Refusal to sign informed consent form
Neoplasm other than defined as inclusion criteria
All contraindications to SRL (see package insert, appendix)
Persons who are detained officially or legally to an official institute

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00866684

Locations

Germany
Charité Universitätsmedizin, Klinik für Dermatologie, Venerologie und Allergologie
Berlin, Germany, 10117
Germany, Bavaria
Klinikum der LMU München, Medizinische Poliklinik Innenstadt
München, Bavaria, Germany, 80336
Klinikum der LMU München, Klinik und Poliklinik für Dermatologie
München, Bavaria, Germany, 80337
Universität Regensburg, Nephrologie Innere Medizin II
Regensburg, Bavaria, Germany, 93053
Klinikum rechts der Isar, Klinik und Poliklinik für Dermatologie und Allergologie
München, Bavaria, Germany, 80802
Universität Regensburg, Dermatologie
Regensburg, Bavaria, Germany, 93053
Klinikum rechts der Isar, II. Medizinische Klinik und Poliklinik
München, Bavaria, Germany, 81675
Universitätsklinikum Erlangen, Hautklinik
Erlangen, Bavaria, Germany, 91052
Universitätsklinikum Erlangen, Medizinische Klinik IV
Erlangen, Bavaria, Germany, 91054
Germany, North Rhine-Westphalia
Universitätsklinikum Münster, Med. Klinik und Poliklinik D
Münster, North Rhine-Westphalia, Germany, 48149
Universitätsklinikum Münster, Klinik und Poliklinik für Hautkrankheiten
Münster, North Rhine-Westphalia, Germany, 48149
HELIOS Klinikum Wuppertal, Zentrum für Dermatologie, Allergologie und Umweltmedizin
Wuppertal, North Rhine-Westphalia, Germany, 42283
Kliniken der Stadt Köln, Medizinische Klinik I
Köln, North Rhine-Westphalia, Germany, 51109
Germany, Schleswig-Holstein
Universitätsklinikum Schleswig-Holstein, Klinik für Dermatologie, Venerologie und Allergologie
Kiel, Schleswig-Holstein, Germany, 24105
Universitätsklinikum Schleswig-Holstein, Klinik für Nieren- und Hochdruckkrankheiten
Kiel, Schleswig-Holstein, Germany, 24105

Sponsors and Collaborators

Charite University, Berlin, Germany

Investigators

Principal Investigator:

Petra Reinke, Prof. Dr.

Charité Universitätsmedizin Berlin

More Information

No publications provided

Responsible Party:	Charité Universitätsmedizin Berlin, Nephrologie u. internistische Intensivmed. ( Petra Reinke, Prof. Dr. med. )
Study ID Numbers:	PROSKIN 01
Study First Received:	March 19, 2009
Last Updated:	May 18, 2009
ClinicalTrials.gov Identifier:	NCT00866684 History of Changes
Health Authority:	Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Charite University, Berlin, Germany:

renal transplant-patients with high-risk for skin cancer

Study placed in the following topic categories:

Sirolimus
Antimetabolites
Anti-Infective Agents
Cyclosporine
Skin Diseases
Immunologic Factors
Tacrolimus
Skin Neoplasms

Cyclosporins
Immunosuppressive Agents
Anti-Bacterial Agents
Azathioprine
Antifungal Agents
Mycophenolate mofetil
Antirheumatic Agents

Additional relevant MeSH terms:

Antimetabolites
Sirolimus
Anti-Infective Agents
Cyclosporine
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Tacrolimus
Antibiotics, Antineoplastic
Cyclosporins
Anti-Bacterial Agents

Azathioprine
Neoplasms by Site
Therapeutic Uses
Antifungal Agents
Dermatologic Agents
Skin Diseases
Enzyme Inhibitors
Skin Neoplasms
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Antirheumatic Agents

ClinicalTrials.gov processed this record on August 25, 2009