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

Study Overview
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Brief Summary
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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.

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

Conditions
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Kidney Transplantation, Skin Cancer

Intervention / Treatment
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* Drug: Sirolimus
* Drug: Azathioprine
* Drug: Mycophenolate
* Drug: Ciclosporin
* Drug: Tacrolimus


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Patients will receive Sirolimus in addition to their previous immunosuppressive therapy. | Drug: Sirolimus<br>* Dosage form: coated tablet; Dosage: 4-8 micrograms/litre; Route of administration: oral use; Frequency: one tablet per day; Duration: 24 month<br>* Other names: Rapamune, ATC code: L04AA10;|
| Active Comparator: 2<br>Patients will stay on their previous immunosuppressive regimen. | Drug: Azathioprine<br>* Dosage form: Coated tablet; dosage: 1-4 milligrams/kilogram; Frequency: daily; Duration: 24 month<br>* Other names: ATC code: L04AX01;Drug: Mycophenolate<br>* Dosage form: Tablet; dosage: 2 gram; Frequency: daily; Duration: 24 month<br>* Other names: ATC code: L04AA06;Drug: Ciclosporin<br>* Dosage form: Capsule; Dosage: 50-80 micrograms/litre; Frequency: daily; Duration: 24 month<br>* Other names: ATC code: L04AA01;Drug: Tacrolimus<br>* Dosage form: Capsule; dosage: 3-5 micrograms/litre; Frequency: daily; Duration: 24 month<br>* Other names: ATC code: L04AA05;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression of actinic keratosis I and II to III or invasive squamous cell carcinoma (SCC) or incidence/reoccurrence of neoplastic skin tumors |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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renal transplant-patients with high-risk for skin cancer