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 and relates on the other hand on the dosage. 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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Renal Transplant Patients at High-risk for Skin Cancer

Intervention / Treatment
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* Drug: Sirolimus


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 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 (300 mg/dl), Triglycerides > 4 mmol/l (350 mg/dl) Leucopenia < 2500/nl Thrombocytopenia < 90/nl Pregnancy or breastfeeding Women of childbearing age without highly effective contraception 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 Acute infections (mycotic, viral or bacterial) Current intake of other substances with known nephrotoxicity Severe liver dysfunction Current intake of CY3A4-inhibitors (e.g. ketoconazole, voriconazole, itraconazole, telithromycin or clarithromycin) or CY3A4-inductors (rifampicin, rifabutin) sucrose-isomaltase deficiency, fructose intolerance, glucose-galactose intolerance azathioprine: known allergy to azathioprine or 6-mercaptopurine, severe bone marrow dysfunction, pancreatitis, vaccination with live vaccine tacrolimus: known allergy to tacrolimus mycophenolatmofetil: known allergy to mycophenolatmofetil, neutropenia, severe active gastrointestinal tract disease, Lesch-Nyhan syndrome or Kelley-Seegmiller syndrome, current intake of azathioprine cyclosporine: known allergy to cyclosporine, increased intracranial pressure

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 |
| --- | --- |
| Active Comparator: Sirolimus<br>Patients who meet all inclusion criteria will be included into the study and randomised. If converted to Sirolimus (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. | Drug: Sirolimus<br> <br> * Other names: Rapamune®;|
| No Intervention: Standard therapy<br>Patients who will not receive SRL stay on their previous immunosuppressive therapy including one or more of the following drugs: azathioprine, cyclosporine, tacrolimus, mycophenolate-sodium and steroids. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression of actinic keratosis or invasive squamous cell carcinoma (SCC) or incidence/reoccurrence of neoplastic skin tumors | 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) | at month 3 | 
| Progression of actinic keratosis or invasive squamous cell carcinoma (SCC) or incidence/reoccurrence of neoplastic skin tumors | 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) | at month 6 | 
| Progression of actinic keratosis or invasive squamous cell carcinoma (SCC) or incidence/reoccurrence of neoplastic skin tumors | 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) | at month 9 | 
| Progression of actinic keratosis or invasive squamous cell carcinoma (SCC) or incidence/reoccurrence of neoplastic skin tumors | 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) | at month 12 | 
| Progression of actinic keratosis or invasive squamous cell carcinoma (SCC) or incidence/reoccurrence of neoplastic skin tumors | 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) | at month 15 | 
| Progression of actinic keratosis or invasive squamous cell carcinoma (SCC) or incidence/reoccurrence of neoplastic skin tumors | 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) | at month 18 | 
| Progression of actinic keratosis or invasive squamous cell carcinoma (SCC) or incidence/reoccurrence of neoplastic skin tumors | 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) | at month 21 | 
| Progression of actinic keratosis or invasive squamous cell carcinoma (SCC) or incidence/reoccurrence of neoplastic skin tumors | 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) | at month 24 |