Renal cell carcinomas arise from the proximal tubal epithelium. Alternatively known as clear-cell cancer or renal adenocarcinoma, RCC is characterized by a distinct clear or granular cell appearance visible by light microscopy. The most common molecular abnormality in clear cell RCC is loss of Von Hippel-Lindau (VHL), which is found in about 50-70% of sporadic cases. MedDRA version: 9.1 Level: LLT Classification code 10050513 Term: Metastatic renal cell carcinoma
Conditions
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Age = 18 years old • Patients with metastatic carcinoma and with histological or cytological confirmation of clear cell RCC (tissue from the original diagnosis of renal cancer is acceptable). • Patients must have progression on or within 6 months of stopping treatment with a VEGF receptor tyrosine kinase inhibitor (sunitinib and/or sorafenib). Patients may have received one or both agents. • Prior therapy with cytokines (i.e., IL-2, Interferon) and/or VEGF-ligand inhibitors (i.e., bevacizumab) are permitted. • Prior vaccine therapy in the adjuvant setting is permitted. • Patients with at least one measurable lesion at baseline as per the RECIST criteria, either on physical exam or as determined by Computer Tomography (CT) Scan or Magnetic Resonance Imaging (MRI). If skin lesions are reported as target lesions, they must be documented (at baseline and at every physical exam) using color photography and a measuring device (such as a caliper) in clear focus to allow the size of the lesion (s) to be determined from the photograph. • Patients with a Karnofsky Performance Status = 70%. • Adequate bone marrow function as shown by: ANC = 1.5 x 109/L, Platelets = 100 x 109/L, Hb > 9 g/dL. • Adequate liver function: serum bilirubin: = 1.5 x ULN, ALT and AST = 2.5x ULN. Patients with known liver metastases: AST and ALT = 5x ULN. • Adequate renal function: serum creatinine = 1.5 x ULN. • Patients with a life expectancy = 3 months. Life expectancy should be judged in relation to other determining patient eligibility factors such as laboratory results, Karnofsky Performance Status etc.) • Women of childbearing potential must have had a negative serum or urine pre gnancy test within 7 days prior to the administration of the first study treatment. • Patients who give a written informed consent obtained according to local guidelines Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Patients currently receiving chemotherapy, immunotherapy, or radio-therapy or who have received these within 4 weeks of study entry. The wash-out period for Sunitinib and/or Sorafenib is at least 2 weeks from the first dose of the study medication. • Patients who have previously received mTOR inhibitors. • Patients receiving chronic treatment with corticosteroids or another immunosuppressive agent • Patients with a known history of HIV seropositivity • Patients with an active, bleeding diathesis or on oral anti-vitamin K medication (except low dose coumadin) • Patients with a known hypersensitivity to RAD001 (everolimus) or other rapamycins (sirolimus, temsirolimus) or to its excipients. •Patients with untreated CNS metastases or who have received treatment for CNS metastases within 6 months of study entry. Patients with treated CNS metastases, who are neurologically stable and off of corticosteroids for more than 6 months prior to study entry, are eligible to enter study. • Patients who have any severe and/or uncontrolled medical conditions such as: • unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction = 6 months prior to randomization, serious uncontrolled cardiac arrhythmia, • uncontrolled diabetes as defined by fasting serum glucose >1.5X ULN. • active or uncontrolled severe infection. • cirrhosis, chronic active hepatitis or chronic persistent hepatitis • severely impaired lung function • Patients who have a history of another primary malignancy = 3 years, with the exceptions of non-melanoma skin cancer, and carcinoma in situ of uterine cervix • Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods. If barrier contraceptives are being used, these must be continued throughout the trial by both sexes. • Patients who are using other investigational agents or who had received investigational drugs = 4 weeks prior to Visit 1. • Patients unwilling to or unable to comply with the protocol
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare progression-free survival (PFS) in patients who receive RAD001 plus BSC versus patients who receive Matching Placebo plus BSC.;Secondary Objective: • To compare the overall survival for patients who received RAD001 plus BSC versus Matching Placebo plus BSC • To compare the objective response rate and duration in patients who receive RAD001 plus BSC versus Matching Placebo plus BSC • To describe the safety profile of RAD001 when compared to Placebo • To assess disease related symptoms and overall QoL in patients treated with RAD001 plus BSC and to compare these patients reported outcomes to the Matching Placebo plus BSC treatment group. • To describe the pharmacokinetics of RAD001 in patients with renal cell cancer. • To explore the relationships between RAD001 blood levels and efficacy/safety endpoints.;Primary end point(s): progression-free survival | — |
Countries
Austria, France, Germany, Italy, Netherlands
Outcome results
None listed