Study Evaluating the Effect of Sirolimus on Non-Melanoma Skin Cancer in Kidney Transplant Recipients

Study Overview
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Brief Summary
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The purpose of this study is to determine the effect of sirolimus on the prevention of new non-melanoma skin cancer (NMSC) in kidney transplant recipients.

Official Title
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A Randomized, Open-Label Study to Compare the Rate of New Non-Melanoma Skin Cancer in Maintenance Renal Allograft Recipients Converted to a Sirolimus-based Regimen Versus Continuation of a Calcineurin Inhibitor-based Regimen

Conditions
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Skin Neoplasms, Kidney Transplantation

Intervention / Treatment
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* Drug: sirolimus
* Drug: cyclosporine or tacrolimus


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Kidney transplant at least 1 year prior Subjects with a functioning renal allograft with calculated glomerular filtration rate (GFR) ≥40mL/min (Nankivell method) and proteinuria ≤500mg/day. Stable on cyclosporine or tacrolimus-based multi-drug immunosuppressive regimen History of NMSC within last 3 years Exclusion Criteria: History of other cancer within last 3 years NMSC with metastatic disease or more than 20 NMSC lesions in last 12 months Multiple organ transplant

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Conversion to a sirolimus-based regimen | Drug: sirolimus<br> <br> |
| Active Comparator: 2<br>Continuation of a CNI-based regimen | Drug: cyclosporine or tacrolimus<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| New Biopsy-Confirmed Nonmelanoma Skin Cancer (NMSC) Lesions Per Subject Per Year | The number of new biopsy-confirmed NMSC lesions per subject per year was calculated by summarizing the total number of new BCC and SCC lesions reported over the observation period and standardizing it to an annual rate by multiplying by 365 and dividing by days on study. | up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to First Biopsy Confirmed New NMSC Lesion. | The time to first biopsy confirmed new NMSC lesion starts at 1 day post randomization to biopsy and/or treatment of newly confirmed NMSC lesion. | up to 24 months | 
| Number of Lesion Free Subjects | The overall number of subjects who were lesion free were compared between treatment groups with the Cochran Mantel Haenszel test stratified by baseline NMSC stratum. Within each stratum, the Fisher exact test was used to compare the proportions of lesion free subjects between treatment groups. | up to 24 months | 
| Percentage of Patients With New Biopsy-confirmed NMSC: Squamous Cell Carcinoma (SCC) and Basal Cell Carcinoma (BCC) |  | up to 24 months | 
| Grade Distribution of NMSC Lesions | Number of subjects with at least 1 biopsy-confirmed new squamous cell carcinoma (SCC) or basal cell carcinoma (BCC). | up to 24 months | 
| Number of Recurrent NMSC Lesions Per Subject-year | Recurrent NMSC lesions is defined as recurring at the site of a previously treated lesion. | up to 24 months | 
| Subjects Reporting Incidence of Metastatic Disease Related to NMSC. | The number of subjects with metastatic disease related to NMSC. | up to 24 months | 
| Death Due to NMSC |  | up to 24 months | 
| Number of Subjects Who Discontinue Assigned Therapy |  | up to 24 months | 
| Nankivell-Calculated Glomerular Filtration Rate (GFR) | GFR is an index of kidney function. GFR describes the flow rate of filtered fluid through the kidney. GFR can be measured directly or estimated using established formulas. For this study, GFR was calculated using Nankivell. A normal GFR is > 90 mL/min, although children and older people usually have a lower GFR. Lower values indicate poor kidney function. A GFR <15 is consistent with kidney failure. | At 24 months (week 104) | 
| Serum Creatinine Level | Serum creatinine is an indicator of kidney function. Creatinine is a substance formed from the metabolism of creatinine, commonly found in blood, urine, and muscle tissue. It is removed from the blood by the kidneys and excreted in urine. An increased level of creatinine in the blood indicates decreased kidney function. Normal adult blood levels of creatinine are 0.5 to 1.1 mg/dL for females and 0.6 to 1.2 mg/dL for males, however the normal values are age-dependent as elderly patients typically have smaller muscle mass. | At 24 months (Week 104) | 
| Number of Participants That Died |  | up to 24 months | 
| Graft Survival Measured by Graft Loss | Graft loss was defined as physical loss (nephrectomy), functional loss (necessitating maintenance dialysis for >8 consecutive weeks), retransplant, or death. | up to 24 months | 
| Number of Subjects With Biopsy-Confirmed Acute Rejection |  | up to 24 months | 
| Spot Urine Protein:Creatinine Ratio | Subjects' urine protein:creatinine ratios were summarized by each scheduled visit, and the nonparametric Wilcoxon rank sum test was used to compare the difference between groups. | At 24 months (Week 104) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Kidney, Transplant, Skin Cancer