Title Phase II study of oral PRednisone 5 mg bid plus EVerolimus in patients with metastatic renal cell cancer after failure of vascular endothelial growth factor receptor-tyrosine kinase inhibitor (PREV study).~Short Title/ Acronym PREV Protocol Code IRST189.04 Phase Phase 2 Study Design This is a multicenter prospective study that includes all patients with metastatic RCC pre- treated with VEGFR TKI in eight Italian cancer centers.~Study Duration 2 years of recruitment and 1 year of follow-up Study Center(s) multi-center: 8 centers involved~Objectives Primary objective:~To evaluate the safety and tolerability of prednisone 5 mg bid and everolimus 10 mg/day in RCC.~Secondary objectives:~To evaluate the activity and the clinical outcome of these patients.~Exploratory objectives:~To evaluate the influence of prednisone on trough concentration of everolimus and correlation with the incidence of side effects, in particular stomatitis and non-infectious pneumonitis.~Infiammation markers such as pentraxin 3 (PTX3), IL-6, TGF-β and neutrophil-lymphocyte ratio will be correlated with clinical outcome (ORR, PFS, OS).~Number of Subjects 42 subjects Diagnosis and Main Inclusion Criteria Patients with mRCC who failed at least one VEGFR TKI.~Main Inclusion Criteria:~Patients with renal cell carcinoma who failed at least one VEGFR TKI~Patients with adequate bone marrow function~Patients with adequate liver function~Patients with adequate renal function Diagnosis and Main Inclusion Criteria (continued) Main exclusion criteria:~CNS disease OR patients with presence or history of central nervous system (CNS) lymphoma~Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent (except corticosteroids with a daily dosage equivalent to prednisone ≤ 20 mg for adrenal insufficiency). However, patients receiving corticosteroids must be on a stable dose for ≥ 4 weeks prior to the first dose of everolimus. Topical or inhaled corticosteroids are permitted.~Patients with a known hypersensitivity to everolimus or other rapamycins (sirolimus, temsirolimus) or to its excipients~Patients with uncontrolled hyperlipidemia (≥ Grade 3 hyperlipidemia despite optimal supportive medical therapy)~Patients with an active, bleeding diathesis~Previous organ transplantation~Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study Study Product, Dose, Route, Regimen and duration of administration Everolimus is formulated as tablets of 5-10 mg strength, blister-packed under aluminium foil in units of 10 tablets. Prednisone will be dispensed to patients at the dose of 5 mg twice daily (BID). Everolimus at dose of 10 mg (one 10 mg tablet or two 5 mg tablets). Both drugs will be self-administered orally, continuously from Day 1 (Visit 2) until progression of disease, unacceptable toxicity, death or discontinuation for any other reason.~A treatment cycle consists of 28 days. Reference therapy Not applicable Statistical Methodology This is a multicenter prospective study that includes all patients with metastatic RCC pre- treated with VEGFR TKI in eight Italian cancer centers.~The study will be analyzed on an intent-to-treat basis. Secondary parameters will be analyzed exploratively for the intent-to-treat population.
This is a multicenter prospective study that includes all patients with metastatic Renal Cell Cancer (RCC) pre- treated with VEGFR TKI in eight Italian cancer centers.~Everolimus is formulated as tablets of 5-10 mg strength, blister-packed under aluminium foil in units of 10 tablets. Prednisone will be dispensed to patients at the dose of 5 mg twice daily (BID). Everolimus at dose of 10 mg (one 10 mg tablet or two 5 mg tablets). Both drugs will be self-administered orally, continuously from Day 1 (Visit 2) until progression of disease, unacceptable toxicity, death or discontinuation for any other reason.~A treatment cycle consists of 28 days.