Clinical trial NCT01797315: Prevention of Skin Cancer in High Risk Patients After Conversion to a Sirolimus-based Immunosuppressive Protocol
Official title: Prevention of Skin Cancer in High Risk Patients After Conversion to a Sirolimus-based Immunosuppressive Protocol
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Renal Transplant Patients at High-risk for Skin Cancer
Lead sponsor: University Hospital of Berlin
Sponsor class: OTHER
First posted: 2013-02-22
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Transplant recipients have a high risk to develop skin malignancies. This effect depends on the one hand on the immunosuppressive drugs themselves and relates on the other hand on the dosage. 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.


Eligibility criteria: 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
* 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 (300 mg/dl), Triglycerides \> 4 mmol/l (350 mg/dl)
* Leucopenia \< 2500/nl
* Thrombocytopenia \< 90/nl
* Pregnancy or breastfeeding
* Women of childbearing age without highly effective contraception
* 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
* Acute infections (mycotic, viral or bacterial)
* Current intake of other substances with known nephrotoxicity
* Severe liver dysfunction
* Current intake of CY3A4-inhibitors (e.g. ketoconazole, voriconazole, itraconazole, telithromycin or clarithromycin) or CY3A4-inductors (rifampicin, rifabutin)
* sucrose-isomaltase deficiency, fructose intolerance, glucose-galactose intolerance
* azathioprine: known allergy to azathioprine or 6-mercaptopurine, severe bone marrow dysfunction, pancreatitis, vaccination with live vaccine
* tacrolimus: known allergy to tacrolimus
* mycophenolatmofetil: known allergy to mycophenolatmofetil, neutropenia, severe active gastrointestinal tract disease, Lesch-Nyhan syndrome or Kelley-Seegmiller syndrome, current intake of azathioprine
* cyclosporine: known allergy to cyclosporine, increased intracranial pressure

Primary outcomes:
measure: Progression of actinic keratosis or invasive squamous cell carcinoma (SCC) or incidence/reoccurrence of neoplastic skin tumors
timeFrame: at month 3
measure: Progression of actinic keratosis or invasive squamous cell carcinoma (SCC) or incidence/reoccurrence of neoplastic skin tumors
timeFrame: at month 6
measure: Progression of actinic keratosis or invasive squamous cell carcinoma (SCC) or incidence/reoccurrence of neoplastic skin tumors
timeFrame: at month 9
measure: Progression of actinic keratosis or invasive squamous cell carcinoma (SCC) or incidence/reoccurrence of neoplastic skin tumors
timeFrame: at month 12
measure: Progression of actinic keratosis or invasive squamous cell carcinoma (SCC) or incidence/reoccurrence of neoplastic skin tumors
timeFrame: at month 15
measure: Progression of actinic keratosis or invasive squamous cell carcinoma (SCC) or incidence/reoccurrence of neoplastic skin tumors
timeFrame: at month 18
measure: Progression of actinic keratosis or invasive squamous cell carcinoma (SCC) or incidence/reoccurrence of neoplastic skin tumors
timeFrame: at month 21
measure: Progression of actinic keratosis or invasive squamous cell carcinoma (SCC) or incidence/reoccurrence of neoplastic skin tumors
timeFrame: at month 24
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
References: