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

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.

Study Overview

• Status: Terminated
• Conditions: Kidney Transplantation; Skin Cancer
• Intervention / Treatment: Drug: Sirolimus; Drug: Azathioprine; Drug: Mycophenolate; Drug: Ciclosporin; Drug: Tacrolimus

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 4

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; 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; Other Names: Rapamune, ATC code: L04AA10
Active Comparator: 2; Patients will stay on their previous immunosuppressive regimen.	Drug: Azathioprine; Dosage form: Coated tablet; dosage: 1-4 milligrams/kilogram; Frequency: daily; Duration: 24 month; Other Names: ATC code: L04AX01; Drug: Mycophenolate; Dosage form: Tablet; dosage: 2 gram; Frequency: daily; Duration: 24 month; Other Names: ATC code: L04AA06; Drug: Ciclosporin; Dosage form: Capsule; Dosage: 50-80 micrograms/litre; Frequency: daily; Duration: 24 month; Other Names: ATC code: L04AA01; Drug: Tacrolimus; Dosage form: Capsule; dosage: 3-5 micrograms/litre; Frequency: daily; Duration: 24 month; Other Names: ATC code: L04AA05

What is the study measuring?

Primary Outcome Measures

Outcome Measure
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
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

Collaborators and Investigators

• Sponsor: Charite University, Berlin, Germany
• Investigators: Principal Investigator: Petra Reinke, Prof. Dr., Charite University, Berlin, Germany

Study record dates

Study Major Dates

• Study Start: January 1, 2007
• Primary Completion (Actual): January 1, 2011
• Study Completion (Actual): July 1, 2011

Study Registration Dates

• First Submitted: March 19, 2009
• First Submitted That Met QC Criteria: March 19, 2009
• First Posted (Estimate): March 20, 2009

Study Record Updates

• Last Update Posted (Estimate): September 2, 2015
• Last Update Submitted That Met QC Criteria: September 1, 2015
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Keywords: renal transplant-patients with high-risk for skin cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Skin Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Calcineurin Inhibitors; Azathioprine; Tacrolimus; Sirolimus; Cyclosporine; Cyclosporins
• Other Study ID Numbers: PROSKIN 01