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

Civil Hospices of Lyon

Status and phase

Completed

Phase 3

Conditions

Cardiac Transplantation

Skin Cancer

Treatments

Drug: Everolimus

Study type

Interventional

Funder types

Other

Identifiers

NCT00799188

2007.489/32

Details and patient eligibility

About

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.

Full 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

Enrollment

175 patients

Sex

All

Ages

18 to 65 years old

Volunteers

No Healthy Volunteers

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