renal cell cancer
Conditions
Interventions
Study treatment will start on Day 1, Cycle 1 until progression of disease (per
the investigator), unacceptable toxicity, death or discontinuation from the
study for any other reason. A treatment cyc
bevacizumab
kidney carcinoma
RAD001
Sponsors
Novartis
Eligibility
Age
18 Years to 64 Years
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 with progressive metastatic renal cell carcinoma (by RECIST criteria) requiring treatment. 5. Patients who had a prior partial or complete nephrectomy. Partial nephrectomy is allowed only if the resection margins were clearly negative. 6. Patients with a Karnofsky Performance Status >=70%. 7. Adequate bone marrow function as shown by: ANC >= 1.5 x 109/L, Platelets >= 100 x 109/L, Hb >9 g/dL. 8. Adequate liver function: serum bilirubin: 2 weeks at time of randomization.) 11. Adequate lipid profile: total cholesterol
Exclusion criteria
Exclusion criteria: 1. Patients within 4 weeks post-major surgery (e.g., intra-thoracic, intraabdominal 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 4 weeks 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 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 IFN 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary: To assess the treatment effect on progression-free survival (PFS) of patients who receive RAD001 plus bevacizumab versus patients who receive IFN plus bevacizumab, in order to estimate the chance of success of a possible subsequent phase III study. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary: • To estimate the overall survival (OS) treatment effect in patients who receive RAD001 plus bevacizumab versus patients who receive IFN plus bevacizumab. • To estimate the objective response rate and response duration differences in patients who receive RAD001 plus bevacizumab versus patients who receive IFN plus bevacizumab. • To describe the safety profile of RAD001 plus bevacizumab versus IFN plus bevacizumab. • To estimate patient reported outcomes on quality of life (QoL) from patients treated with RAD001 plus bevacizumab versus patients treated with IFN plus bevacizumab. • To measure the exposure of RAD001 in patients randomized to the treatment combination of RAD001 plus bevacizumab. Exploratory: • To determine the effects of RAD001 on plasma angiogenic molecules e.g., VEGF, basic FGF, PLGF, sVEGFR1, and sVEGFR2 and other markers of hypoxia e.g., LD isoenzyme 5 and carbonic anhydrase IX (CA9). • To characterize pre-treatment tumor samples by immunohistochemical and genetic analyses for activation of the mTOR and angiogenic/hypoxia pathways. • Relationships between response and RAD001 Cmin will be explored. RAD001 Cmin represents the minimum exposure of the drug in blood during daily administration. Exploration of the relationship between RAD001 Cmin and response helps to determine the minimum effective concentration of RAD001 in the target patient population. | — |
Countries
Netherlands
Outcome results
None listed