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

Charité University Medicine Berlin

Status and phase: Terminated; Phase 4

Conditions: Skin Cancer

Treatments: Drug: Ciclosporin; Drug: Sirolimus; Drug: Azathioprine; Drug: Mycophenolate; Drug: Tacrolimus

Study type: Interventional

Funder types: Other

Identifiers

NCT00866684

PROSKIN 01

Details and patient eligibility

About

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.

Full 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.

Enrollment: 44 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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44 participants in 2 patient groups

1 Sirolimus

Experimental group

Description:

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

Treatment:

Drug: Sirolimus

2 Standard

Active Comparator group

Description:

Patients will stay on their previous immunosuppressive regimen.

Treatment:

Drug: Tacrolimus

Drug: Mycophenolate

Drug: Azathioprine

Drug: Ciclosporin