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

Phase 4
Completed
Conditions
Skin Neoplasms
Kidney Transplantation
Interventions
Registration Number
NCT00129961
Lead Sponsor
Wyeth is now a wholly owned subsidiary of Pfizer
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
86
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
2cyclosporine or tacrolimusContinuation of a CNI-based regimen
1sirolimusConversion to a sirolimus-based regimen
Primary Outcome Measures
NameTimeMethod
New Biopsy-Confirmed Nonmelanoma Skin Cancer (NMSC) Lesions Per Subject Per Yearup to 24 months

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.

Secondary Outcome Measures
NameTimeMethod
Time to First Biopsy Confirmed New NMSC Lesion.up to 24 months

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.

Number of Lesion Free Subjectsup to 24 months

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.

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 Lesionsup to 24 months

Number of subjects with at least 1 biopsy-confirmed new squamous cell carcinoma (SCC) or basal cell carcinoma (BCC).

Number of Recurrent NMSC Lesions Per Subject-yearup to 24 months

Recurrent NMSC lesions is defined as recurring at the site of a previously treated lesion.

Subjects Reporting Incidence of Metastatic Disease Related to NMSC.up to 24 months

The number of subjects with metastatic disease related to NMSC.

Death Due to NMSCup to 24 months
Number of Subjects Who Discontinue Assigned Therapyup to 24 months
Nankivell-Calculated Glomerular Filtration Rate (GFR)At 24 months (week 104)

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.

Serum Creatinine LevelAt 24 months (Week 104)

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.

Number of Participants That Diedup to 24 months
Graft Survival Measured by Graft Lossup to 24 months

Graft loss was defined as physical loss (nephrectomy), functional loss (necessitating maintenance dialysis for \>8 consecutive weeks), retransplant, or death.

Number of Subjects With Biopsy-Confirmed Acute Rejectionup to 24 months
Spot Urine Protein:Creatinine RatioAt 24 months (Week 104)

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.

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