E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Squamous cell carcinoma (SCC) and other malignancies in renal transplanted recipients |
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E.1.1.1 | Medical condition in easily understood language |
Squamous cell carcinoma and other malignancies in renal transplanted recipients |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10041823 |
E.1.2 | Term | Squamous cell carcinoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective is to investigate whether initiation of everolimus and discontinuation/ minimization of calcineurin inhibitors (CNI) in maintenance renal transplant patients with at least one earlier diagnosed SCC incident within the last two years prior to inclusion, will reduce the risk of new SCC incidents (per definition, SCC includes SCC in situ (Mb Bowen) and keratoacanthoma (KA) like SCC). |
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E.2.2 | Secondary objectives of the trial |
• Compare time to first SCC event between the two groups (Kaplan Meyer of SCC survival time)
• To compare the risk of developing SCCs at 24 months
• To compare the risk of developing new skin cancers except SCC at 24 months
• To compare the risk of developing cancer except skin cancer at 24 months
• To compare the rate of biopsy proven acute rejections (BPAR) at 24 months
• To compare patient and graft survival at 24 months
• To compare estimated glomerular filtration rate (eGFR) using Modification of Diet in Renal Disease (MDRD) formula between the two groups at 24 months
• To compare adverse event rates
• To compare rates of incidence and type of infections
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female kidney transplant recipients or combined kidney/pancreas transplant recipients aged 18 years or older
2. Patient transplanted at least 12 months prior to enrollment/inclusion
3. Patient has experienced at least one SCC (per definition, SCC includes SCC in situ (Mb Bowen) and keratoacanthoma (KA) like SCC) within the last 2 years
4. Patients receiving a standard immunosuppressive treatment with CNI, +/- mycophenolate acid (MPA), +/- steroids and/or +/- azathioprine (AZA)
5. Patient willing and capable of giving written informed consent for study participation
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E.4 | Principal exclusion criteria |
1. Patients with any present malignancy (other than SCC, basal cell carcinoma or melanoma skin cancer; thickness ≤ 1 mm)
2. Patients who have received an unlicensed drug or therapy within one month prior to study entry or if such therapy is to be instituted post-transplantation
3. Patients with an eGFR (MDRD formula) of < 20 mL/min
4. Patients with on-going treatment for rejection
5. Patients with a hemoglobin count < 8.0 g/dL (5.0 mmol/L); and/or a platelet count < 50x10^9/L and/or white blood cell count ≤ 2.5x10^9/L
6. Patients with total cholesterol (TC) ≥ 9 mmol/L and/or triglycerides (TG) ≥ 6 mmol/L despite lipid lowering treatment
7. Patients with a spot urinary albumin/creatinine ratio ≥ 50 mg/mmol
8. Patient with a current clinically severe systemic infection
9. Patients treated with everolimus or sirolimus within the past 12 months
10. Patients unable to participate in the study for the full 24-months period
11. Female patients of childbearing potential not able to present a negative pregnancy test prior to randomization
12. Nursing mothers
13. Known hypersensitivity to any of the study drugs (or excipients) or to macrolides
14. Patients with high immunological risk profile
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the proportion of patients who developed at least one new SCC during the 24 month study period. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Suspected new SCCs will be assessed at least every 6 months or by indication during a period of 24 months |
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E.5.2 | Secondary end point(s) |
1. Suspected new skin cancers; Skin biopsy to be performed according to standard procedure and parameteres to be recorded are type of malignant skin cancer, SCC in situ (Mb Bowen), and Actinictic keratosis.
2. New malignancies exept skin cancers
3. Renal function analysed as eGFR ( Modification of Diet in Renal Disease formula)
4. Acute rejection episodes
5. Graft loss (suspected if the patient start dialysis and is not subsequently to be removed)
6. Adverse events rates
7. Rates of incidence and types of infections
6. Patient survival |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
These end points will be assessed at the following timepoints;
1. At visit 2 (baseline), and visit 7-11 or at least every 3-6 months. Suspected new SCC incidents will be assessed by indication (if applicable).
2. At visit 2 - visit 11.
3. At visit 1 (enrollment visit) - visit 11.
4. At visit 3-11 (if applicable)
5. At visit 3-11 (if applicable)
6. At visit 2-11
7. At visit 3-11 (if applicable)
6. At visit 11 (24 months) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
This is an open-label study. The Pathologist assessing the biopsy will be blinded to treatment arms. |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 7 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |