Condition category
Date applied
Date assigned
Last edited
Retrospectively registered
Overall trial status
Recruitment status
No longer recruiting
Publication status

Plain English Summary

Not provided at time of registration

Trial website

Contact information



Primary contact

Dr J W de Fijter


Contact details

Leiden University Medical Centrw
Department of Nephrology
P.O. Box 9600
2300 RC
+31 (0)71 526 2169

Additional identifiers

EudraCT number number

Protocol/serial number


Study information

Scientific title

A randomised, prospective, open-label, multi-centre study comparing the efficacy and safety of conversion to sirolimus in stable renal or liver transplant recipients with a cutaneous squamous cell carcinoma



Study hypothesis

It is hypothesised that conversion to a regimen with Rapamune® (sirolimus), an effective immunosuppressive drug with antiproliferative properties, could diminish the recurrence rate of cutaneous squamous cell carcinoma (SCC). The potential usefulness of sirolimus in the prevention of (recurrent) skin carcinoma is suggested not only by in vitro and pre-clinical studies, but also by preliminary results from studies in renal transplant recipients.

Ethics approval

Approval received from the local medical ethics committee

Study design

Multicentre, randomised, double blind, active controlled, parallel group trial

Primary study design


Secondary study design

Randomised controlled trial

Trial setting


Trial type


Patient information sheet


Squamous cell carcinoma (SCC)


Sirolimus treatment arm: conversion to sirolimus:
1. At the time of randomisation the patient stops the purine antagonist (azathioprine or mycophenolate mofetil) or the calcineurin inhibitor (cyclosporine or tacrolimus) on day zero and starts the same day with sirolimus (day zero: loading dose; day one: maintenance dose). Between days five and seven 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 range of 5 - 10 ng/ml.

Intervention type



Not Specified

Drug names

Sirolimus (Rapamune®)

Primary outcome measure

To determine the recurrence rate of biopsy-confirmed cutaneous SCC with sirolimus (SRL)-based immunosuppression over a two year period of follow-up.

Secondary outcome measures

1. Number of hyperkeratotic skin lesions, located on: the dorsum of the hands, the forearms, the head.

Secondary safety:
2. Incidence and severity of biopsy-confirmed acute rejection
3. Treatment failure, defined as the occurrence of acute rejection or premature withdrawal from study medication for any reason
4. Differences in renal function as estimated by the Cockcroft-Gault equation in both renal and liver transplant recipients
5. Patient and graft survival

Overall trial start date


Overall trial end date


Reason abandoned (if study stopped)


Participant inclusion criteria

1. Organ (kidney or liver) transplant recipient with biopsy-confirmed cutaneous SCC
2. Aged over 18 years and at least 12 months post-transplantation
3. Stable graft function (estimated glomerular filtration rate [GFR] more than 20 ml/min) while on a maintenance regimen with a calcineurin inhibitor, azathioprine, mycophenolate mofetil or steroids for at least 12 weeks before randomisation
4. No acute rejection episode within 12 weeks prior to randomisation
5. All female patients at risk for pregnancy must have a negative serum pregnancy test before randomisation. 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 more than 3000/mm^3, platelet count more than 75,000/mm^3
7. Fasting triglycerides less than 3.95mmol/l, cholesterol less than 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

Participant type


Age group




Target number of participants


Participant 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 bilirubin level (for liver allograft recipient) at screening that has increased by more than 30% above the last value obtained at least 12 weeks earlier
4. Evidence of systemic infection at the time of randomisation
5. Prior or current use of SRL or any of its derivatives
6. Use of investigational agents for less than four weeks before randomisation, except for topical dermatological products as Aldara® (imiquimod) or Efudix® (5-fluoro-uracil)
7. Use of immunosuppressive agents (at the time of randomisation) other than calcineurin inhibitor, azathioprine, mycophenolate mofetil or prednisone
8. Current use of terfenadine, cisapride, astemizole, pimozide, or cimetidine; these drugs must be discontinued before randomisation
9. Positive past medical history for documented human immunodeficiency virus (HIV) infection

Recruitment start date


Recruitment end date



Countries of recruitment


Trial participating centre

Leiden University Medical Centrw
2300 RC

Sponsor information


Wyeth Pharmaceuticals B.V. (The Netherlands)

Sponsor details

P.O. Box 255
2130 AG
+31 (0)23 5672567

Sponsor type

Not defined



Funder type

Not defined

Funder name

Not provided at time of registration

Alternative name(s)

Funding Body Type

Funding Body Subtype


Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Basic results (scientific)

Publication list

1. 2013 results in

Publication citations

  1. Results

    Hoogendijk-van den Akker JM, Harden PN, Hoitsma AJ, Proby CM, Wolterbeek R, Bouwes Bavinck JN, de Fijter JW, Two-year randomized controlled prospective trial converting treatment of stable renal transplant recipients with cutaneous invasive squamous cell carcinomas to sirolimus., J. Clin. Oncol., 2013, 31, 10, 1317-1323, doi: 10.1200/JCO.2012.45.6376.

Additional files

Editorial Notes