Clinical trial NCT00799188: CERTICOEUR: A Secondary Prevention Study of Skin Cancers in Heart Transplant Patients. Everolimus Versus Calcineurin Inhibitors Multicenter Trial
Official title: CERTICOEUR a Secondary Prevention Study of Skin Cancers in Heart Transplant Patients. An Open Labelled Randomized Everolimus vs Calcineurin Inhibitors Multicenter Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Cardiac Transplantation
Skin Cancer
Keywords: Cardiac Transplantation
Skin cancer
Everolimus
Lead sponsor: Hospices Civils de Lyon
Sponsor class: OTHER
First posted: 2008-11-27
Enrollment: 175
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: * 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

Eligibility criteria: 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

Primary outcomes:
measure: Number of skin tumors per patients requiring surgery with histology control within 2 years
timeFrame: 2 years
Secondary outcomes:
measure: New skin cancer
timeFrame: 2 years
measure: Number of patients with new skin cancers
timeFrame: 2 years
measure: Time of recurrence
timeFrame: 2 years
measure: Number and histology of other types of skin cancer
timeFrame: 2 years
measure: Graft function (including acute rejection, graft loss, death)
timeFrame: 2 years
measure: Renal function evolution as assessed using Cockcroft creatinine clearance and proteinuria
timeFrame: 2 years
measure: Adverse events and serious adverse events
timeFrame: 2 years
measure: Non skin cancer (Number and diagnostic)
timeFrame: 2 years
measure: Schemes of calcineurin inhibitors reduction/withdrawal
timeFrame: 2 years
measure: Immune response assessment through regulatory or effector function of blood and in situ T lymphocytes at baseline and following immunosuppression switch
timeFrame: 2 years
Other outcomes:
Locations:
city: Lyon
country: France
facility: HOSPICES CIVILS de LYON
Study officials:
affiliation: Hospices Civils de Lyon
name: LAURENT SEBBAG, MD
role: PRINCIPAL_INVESTIGATOR
References: