Patients with metastatic clear cell carcinoma of the kidney 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: 1. Age = 18 years old 2. Patients with metastatic renal cell carcinoma and with histological or cytological confirmation of clear cell RCC (pathology report based on the tissue from the original diagnosis of renal cell cancer is acceptable). Any percentage of clear cell histology is acceptable. 3. Patients with at least one measurable lesion at baseline as per the RECIST criteria. 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. 4. Patients who had a prior partial or complete nephrectomy. Partial nephrectomy is allowed only if the resection margins were clearly negative. 5. Patients with a Karnofsky Performance Status =70%. 6. Adequate bone marrow function as shown by: ANC = 1.5 x 109/L, Platelets = 100 x 109/L, Hb >9 g/dL. 7. 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. 8. Adequate renal function: serum creatinine = 2.0 x ULN. 9. INR and PTT 2 weeks at time of randomization.) 10. Adequate lipid profile: total cholesterol =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Patients within 4 weeks post-major surgery (e.g., intra-thoracic, intra-abdominal or intra-pelvic), open biopsy, or significant traumatic injury to avoid wound healing complications. Minor procedures and percutaneous biopsies or placement of vascular access device require 7 days prior to study entry. 2. Patients who had radiation therapy within 28 days prior to start of study treatment (palliative radiotherapy to bone lesions allowed within 2 weeks prior to study treatment start). 3. Patients in anticipation of the need for major surgical procedure during the course of the study. 4. Patients with a serious non-healing wound, ulcer, or bone fracture. 5. Patients with a history of seizure(s) not controlled with standard medical therapy. 6. Patients who have received prior systemic treatment for their metastatic RCC. Adjuvant immunotherapy (vaccines acceptable, but no cytokines) completed 3 months prior to study treatment start is acceptable. 7. Patients who received prior therapy with VEGF pathway inhibitor (even in the adjuvant setting), such as sunitinib, sorafenib, and bevacizumab. 8. Patients who have previously received systemic mTOR inhibitors (sirolimus, temsirolimus, everolimus). 9. Patients with a known hypersensitivity to RAD001 (everolimus) or other rapamycins (sirolimus, temsirolimus) or to its excipients. 10. Patients with evidence of current central nervous system (CNS) metastases or spinal cord compression. 11. Patients with a history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment. 12. Patients with proteinuria at screening as demonstrated by either: • Urine protein: creatinine (UPC) ratio ? 1.0 at screening. • Urine dipstick for proteinuria = 2+ (patients discovered to have =2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate = 1g of protein in 24 hours to be eligible). 13. Patients with inadequately controlled hypertension (defined as a blood pressure of > 150 mmHg systolic and/or > 100 mmHg diastolic on medication), or any prior history of hypertensive crisis or hypertensive encephalopathy. 14. Patients receiving ongoing or with recent (within 10 days prior to study treatment start) need for full therapeutic dose of oral or parenteral anticoagulants or chronic daily treatment with aspirin (> 325 mg/day) or clopidogrel (>75 mg/day). 15. Patients receiving chronic systemic treatment with corticosteroids (dose of = 10 mg/day methylprednisone equivalent) or another immunosuppressive agent. Inhaled and topical steroids are acceptable. 16. Patients with a known history of HIV seropositivity. 17. Patients with hypersensitivity to interferon alfa-2a or any component of the product. 18. Patients with an active, bleeding diathesis or coagulopathy or recurrent thromboembolism (>1 episode of DVT/PE during the past year). 19. Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as: • unstable angina pectoris, symptomatic congestive heart failure (NYHA II, III, IV), myocardial infarction = 6 months prior to first study treatment, serious uncontrolled cardiac arrhythmia, cerebrovascular accidents = 6 months before study treatment start • severely impaired lung function as defined as spirometry and DLCO that is 50% of the normal predicted value and/or 02 saturation that is 88% or less at rest on room air
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the treatment effect on progression-free survival (PFS) of RAD001 plus bevacizumab versus patients who receive IFN and bevacizumab based on an estimation of the chance of success of a possible subsequent phase III study.;Secondary Objective: • To estimate the overall survival (OS) treatment effect in patients who receive RAD001 plus bevacizumab versus patients who receive IFN and bevacizumab. • To estimate the objective response rate and response duration differences in patients who receive RAD001 plus bevacizumab versus patients who receive IFN and bevacizumab. • To describe the safety profile of RAD001 plus bevacizumab versus IFN and bevacizumab. • To compare patient reported outcomes on quality of life (QoL) from patients treated with RAD001 plus bevacizumab versus patients treated with IFN and bevacizumab. • To measure the exposure of RAD001 in patients randomized to the treatment combination of RAD001 and bevacizumab.;Primary end point(s): Progression-free survival (PFS). Progression-free survival (PFS) is the time from the date of randomization to the date of event defined as the first documented progression or death due to any cause. If a patient has not had an event, progression-free survival is censored at the date of last adequate tumor assessment. | — |
Countries
Belgium, Czech Republic, France, Germany, Hungary, Italy, Netherlands, Slovakia, Spain, United Kingdom
Outcome results
None listed