None listed
Conditions
Interventions
Sirolimus treatment arm:
1. Conversion to sirolimus:
At the time of randomization the patient stops the purine antagonist (azathioprine or mycophenolate mofetil) or the calcineurin inhibitor (cyclos
day 1: maintenance dose).
Between day 5-7 a sirolimus trough level is measured and the dose adjusted to maintain/reach the defined range. (see below)
2. Sirolimus will be given as a loading dose of 8 mg, followed by a maintenance dose of 4 mg. The dose of sirolimus will be adjusted to achieve and maintain a whole blood trough concentration in the r
Sponsors
Wyeth
Eligibility
Inclusion criteria
Inclusion criteria: 1. Organ (kidney or liver) transplant recipient with ³1 biopsy-confirmed cutaneous SCC; 2. Age ³18 years and at least 12 months post-transplantation; 3. Stable graft function (estimated GFR ³20 ml/min) while on a maintenance regimen with a calcineurin inhibitor, azathioprine, mycophenolate mofetil or steroids for at least 12 weeks before randomization; 4. No acute rejection episode within 12 weeks prior to randomization; 5. All female patients at risk for pregnancy must have a negative serum pregnancy test before randomization. Female patients at risk for pregnancy must agree to use a medically acceptable method of contraception throughout the treatment period and for 12 weeks after discontinuation of study medication; 6. Total white blood cell count >3,000/mm3, platelet count >75,000/mm3; 7. Fasting triglycerides <3.95 mmol/l, cholesterol <7.8 mmol/l, with or without statins; 8. Signed, dated, and witnessed (institutional review board (IRB)- or independent ethics committee (IEC)-approved) informed consent before screening and before any tests are performed that are specific to the protocol.
Exclusion criteria
Exclusion criteria: 1. Metastatic cutaneous SCC; 2. Other malignancies (except for other skin cancers), documented after transplantation; 3. Serum creatinine (for renal allograft recipient) or bilirubine level (for liver allograft recipient) at screening that has increased by >30% above the last value obtained at least 12 weeks earlier; 4. Evidence of systemic infection at the time of randomization; 5. Prior or current use of SRL or any of its derivatives; 6. Use of investigational agents £ 4 weeks before randomization, except for topical dermatological products as Aldara (imiquimod) or Efudix (5-fluoro-uracil); 7. Use of immunosuppressive agents (at the time of randomization) other than calcineurine inhibitor, azathioprine, mycophenolate mofetil or prednisone; 8. Current use of terfenadine, cisapride, astemizole, pimozide, or cimetidine; these drugs must be discontinued before randomization; 9. Positive past medical history for documented human immunodeficiency virus (HIV) infection.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To determine the recurrence rate of biopsy-confirmed cutaneous SCC with sirolimus (SRL)-based immunosuppression over a 2 year period of follow-up. | — |
Secondary
| Measure | Time frame |
|---|---|
| Number of hyperkeratotic skin lesions, located on: the dorsum of the hands, the forearms, the head. Secondary Safety: 1. Incidence and severity of biopsy-confirmed acute rejection; 2. Treatment failure, defined as the occurrence of acute rejection or premature withdrawal from study medication for any reason; 3. Differences in renal function as estimated by the Cockcroft-Gault equation in both renal and liver transplant recipients; 4. Patient and graft survival. | — |
Contacts
Public ContactJ.W. Fijter, de
Leiden University Medical Center (LUMC), Department of Nephrology, C3-P22, P.O. Box 9600
Outcome results
None listed