Skin Cancer
Conditions
Keywords
Renal transplant-patients with high-risk for skin cancer
Brief summary
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.
Detailed 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.
Interventions
DRUGSirolimus
Treatment arm Dosage: 4-8 micrograms/litre; Route of administration: oral use; Frequency: one tablet per day
DRUGAzathioprine
control arm Dosage form: Coated tablet; dosage: 1-4 milligrams/kilogram; Frequency: daily; Duration: 24 month
DRUGMycophenolate
Control arm Dosage form: Tablet; dosage: 2 gram; Frequency: daily; Duration: 24 month
DRUGCiclosporin
Control arm Dosage form: Capsule; Dosage: 50-80 micrograms/litre; Frequency: daily; Duration: 24 month
DRUGTacrolimus
Control arm Dosage form: Capsule; dosage: 3-5 micrograms/litre; Frequency: daily; Duration: 24 month
Sponsors
Charite University, Berlin, Germany
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Events of Reoccurrence of Skin Cancer | 24 month | 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) |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 1 Sirolimus Patients will receive Sirolimus in addition to their previous immunosuppressive therapy.
Sirolimus: Treatment arm Dosage adapted to serum level: 4-8 micrograms/litre; Route of administration: oral use; Frequency: once per day (Tablets) | 25 |
| 2 Standard Patients will stay on their previous immunosuppressive regimen.
Azathioprine: control arm Dosage form: Coated tablet; dosage: 1-4 milligrams/kilogram; Frequency: daily; Duration: 24 month
Mycophenolate: Control arm Dosage form: Tablet; dosage: 2 gram; Frequency: daily; Duration: 24 month
Ciclosporin: Control arm Dosage form: Capsule; Dosage adapted to serum level: 50-80 micrograms/litre; Frequency: daily; Duration: 24 month
Tacrolimus: Control arm Dosage form: Capsule; dosage adapted to serum level: 3-5 micrograms/litre; Frequency: daily; Duration: 24 month | 19 |
| Total | 44 |
Baseline characteristics
| Characteristic | 2 Standard | 1 Sirolimus | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 10 Participants | 8 Participants | 18 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants | 17 Participants | 26 Participants |
| Age, Continuous | 59.6 years | 64.4 years | 61.68 years |
| Region of Enrollment Germany | 19 Participants | 25 Participants | 44 Participants |
| Sex: Female, Male Female | 6 Participants | 7 Participants | 13 Participants |
| Sex: Female, Male Male | 13 Participants | 18 Participants | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 25 | 0 / 19 |
| other Total, other adverse events | 19 / 25 | 9 / 19 |
| serious Total, serious adverse events | 15 / 25 | 7 / 19 |
Outcome results
Primary
Number of Events of Reoccurrence of Skin Cancer
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)
Time frame: 24 month
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1 Sirolimus | Number of Events of Reoccurrence of Skin Cancer | 25 Event |
| 2 Standard | Number of Events of Reoccurrence of Skin Cancer | 19 Event |