CERTICOEUR: A Secondary Prevention Study of Skin Cancers in Heart Transplant Patients. Everolimus Versus Calcineurin Inhibitors Multicenter Trial

Study Overview
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Brief Summary
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Heart transplant is a recognized therapeutic strategy in refractory heart failure. Its success is however hampered by severe cancer occurrence and recurrence. The new m-tor inhibiting drugs Sirolimus and Everolimus have shown potential for reducing the incidence of cancer in animal models. They are potent immunosuppressant, antiproliferative and antiangiogenic drugs. This open labelled randomized multicenter study aims at evaluating the beneficial antineoplastic effect of Everolimus in 159 heart transplant patients suffering of recurrent skin cancer. Primary objective is to demonstrate a reduction in the number of new skin cancers. Secondary end point will be time of recurrence, incidence of non skin cancer, graft function following switch (including death), renal function evolution following calcineurin inhibitors reduction or withdrawal, Everolimus tolerance profile, schemes of calcineurin inhibitors reduction management in centers.

Detailed Description
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Open labelled randomized Everolimus vs reduction of calcineurin inhibitors trial. 2:1 randomization design October 10, 2008 159 patients (106 everolimus vs 53 calcineurin inhibitors reduction) 175 patients (117 vs 58) X Not yet recruiting 0 recruiting 0 no longer recruiting Number of skin tumors per patients requiring surgery with histology control within 2 years Within 2 years of Follow up: New skin cancer Number of patients with new skin cancers Time of recurrence Number and histology of other types of skin cancer Graft function (including acute rejection, graft loss, death) Renal function evolution as assessed using Cockcroft creatinine clearance and proteinuria Adverse events and serious adverse events Non skin cancer (Number and diagnostic) Schemes of calcineurin inhibitors reduction/withdrawal Immune response assessment through regulatory or effector function of blood and in situ T lymphocytes at baseline and following immunosuppression switch

Official Title
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CERTICOEUR a Secondary Prevention Study of Skin Cancers in Heart Transplant Patients. An Open Labelled Randomized Everolimus vs Calcineurin Inhibitors Multicenter Trial

Conditions
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Cardiac Transplantation, Skin Cancer

Intervention / Treatment
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* Drug: Everolimus


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: First orthotopic heart transplant after 1st year No rejection within previous 6 Months Occurrence of squamous cell carcinoma, basal cell carcinoma, in situ carcinoma, Bowen disease, premalignant keratosis Recurrence of skin cancers leading to immunosuppressive regimen modifications Removal of a skin lesion in the past three years Above 18 yrs and under contraceptive drugs if applicable Informed consent given Health coverage ongoing Exclusion Criteria: Other non simultaneously transplanted organ recent biopsy proven acute rejection Proteinuria > 1g/l Ongoing infectious disease HIV positivity, Chronic active Hepatitis B or C. Abnormal blood tests: transaminases >= 3UNL, Bilirubin > 34 mmol.l, albumin<35 g/l, spontaneous INR >1,3 Hemoglobin >= 8 g/dl, White Blood Count<= 2 giga/l, platelet count <= 50 giga/l Hypercholesterolemia>= 9 mmol/l, hypertriglyceridemia >= 8,5 mmol/l despite treatment History of macrolid or mTor inhibitor intolerance Previous cancer other than skin in the year prior to enrollment Medical or surgical condition unsuitable for the trial Breast feeding Positive pregnancy test Severe psychiatric disorder Communication or language disability

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: 1<br>reduction of immunosuppression | |
| Experimental: 2<br>switch to Everolimus : 50% reduction of calcineurin inhibitors (ciclosporine or tacrolimus) | Drug: Everolimus<br>* 50% reduction of calcineurin inhibitors daily dose followed by further decrease or withdrawal. Everolimus will be introduced and tapered to a trough level of 6 to 10 microg/l.<br>* Other names: Certican;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of skin tumors per patients requiring surgery with histology control within 2 years |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| New skin cancer |  | 2 years | 
| Number of patients with new skin cancers |  | 2 years | 
| Time of recurrence |  | 2 years | 
| Number and histology of other types of skin cancer |  | 2 years | 
| Graft function (including acute rejection, graft loss, death) |  | 2 years | 
| Renal function evolution as assessed using Cockcroft creatinine clearance and proteinuria |  | 2 years | 
| Adverse events and serious adverse events |  | 2 years | 
| Non skin cancer (Number and diagnostic) |  | 2 years | 
| Schemes of calcineurin inhibitors reduction/withdrawal |  | 2 years | 
| Immune response assessment through regulatory or effector function of blood and in situ T lymphocytes at baseline and following immunosuppression switch |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cardiac Transplantation, Skin cancer, Everolimus