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Prevention of Skin Cancer in High Risk Patients After Conversion to a Sirolimus-based Immunosuppressive Protocol

Registration Number
NCT00866684
Lead Sponsor
Charite University, Berlin, Germany
Brief Summary

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.

Detailed Description

Patients who meet all inclusion criteria will be included into the study and randomised. If converted to SRL, patients will take SRL according to the investigator's instructions and medication label, once daily preferably 4 hours after calcineurin-inhibitor medication or in case without calcineurin-inhibitor co-medication in the morning. The dose of SRL will be correlated to the former immunosuppressive therapy according to the study's conversion protocol.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
44
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
1 SirolimusSirolimusPatients will receive Sirolimus in addition to their previous immunosuppressive therapy.
2 StandardAzathioprinePatients will stay on their previous immunosuppressive regimen.
2 StandardMycophenolatePatients will stay on their previous immunosuppressive regimen.
2 StandardCiclosporinPatients will stay on their previous immunosuppressive regimen.
2 StandardTacrolimusPatients will stay on their previous immunosuppressive regimen.
Primary Outcome Measures
NameTimeMethod
Number of Events of Reoccurrence of Skin Cancer24 month

Progression of actinic keratosis I and II to III or invasive squamous cell carcinoma (SCC) or incidence/reoccurrence of neoplastic skin tumors (namely SCC, basal cell carcinoma, keratoacanthoma, Bowen's disease, precancerous keratoses, actinic keratoses III)

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (15)

Universitätsklinikum Erlangen, Medizinische Klinik IV

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Erlangen, Bavaria, Germany

Universitätsklinikum Münster, Klinik und Poliklinik für Hautkrankheiten

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Münster, North Rhine-Westphalia, Germany

Universitätsklinikum Münster, Med. Klinik und Poliklinik D

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Münster, North Rhine-Westphalia, Germany

Universitätsklinikum Schleswig-Holstein, Klinik für Nieren- und Hochdruckkrankheiten

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Kiel, Schleswig-Holstein, Germany

Universitätsklinikum Schleswig-Holstein, Klinik für Dermatologie, Venerologie und Allergologie

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Kiel, Schleswig-Holstein, Germany

Kliniken der Stadt Köln, Medizinische Klinik I

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Köln, North Rhine-Westphalia, Germany

HELIOS Klinikum Wuppertal, Zentrum für Dermatologie, Allergologie und Umweltmedizin

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Wuppertal, North Rhine-Westphalia, Germany

Universitätsklinikum Erlangen, Hautklinik

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Erlangen, Bavaria, Germany

Klinikum der LMU München, Klinik und Poliklinik für Dermatologie

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München, Bavaria, Germany

Klinikum der LMU München, Medizinische Poliklinik Innenstadt

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München, Bavaria, Germany

Klinikum rechts der Isar, Klinik und Poliklinik für Dermatologie und Allergologie

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München, Bavaria, Germany

Universität Regensburg, Dermatologie

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Regensburg, Bavaria, Germany

Klinikum rechts der Isar, II. Medizinische Klinik und Poliklinik

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München, Bavaria, Germany

Universität Regensburg, Nephrologie Innere Medizin II

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Regensburg, Bavaria, Germany

Charité Universitätsmedizin, Klinik für Dermatologie, Venerologie und Allergologie

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Berlin, Germany

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