metastatic renal cell carcinoma MedDRA version: 16.1 Level: LLT Classification code 10038409 Term: Renal cell carcinoma NOS System Organ Class: 100000004864
Conditions
Sponsors
Novartis Pharma GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients with advanced renal cell carcinoma of a histological or cytological confirmation of clear cell renal carcinoma. 2. Progression during or after a treatment with sunitinib or pazopanib given in a 1st line treatment situation for mRCC. 3. Patients scheduled for treatment with everolimus (Afinitor®). 4. Patients with at least one measurable lesion at baseline as per RECIST-criteria version 1.1. 5. Patients with ECOG PS 0-1. 6. Absolute neutrophile count = 1.5 x 109/L, platelets = 100 x 109/L, Hb > 9 g/dL (5.6 mmol/l). 7. serum bilirubin: = 1.5 x ULN, ALT and AST = 2.5x ULN. Patients with known liver metastases: AST and ALT = 5x ULN. 8. serum creatinine = 2.5 x ULN. 9. Urine protein of =65 years) yes F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
Exclusion criteria: 1. Patients who have received >1 prior systemic treatment for their metastatic RCC. Prior systemic treatment in an adjuvant setting is allowed. 2. Patients who have previously received systemic mTOR inhibitors (e.g. sirolimus, temsirolimus, everolimus). 3. Patients with a known hypersensitivity to everolimus or other rapamycins (sirolimus, temsirolimus) or to its excipients. 4. Patients within 4 weeks post-major surgery (e.g. intra-thoracic, intra-abdominal or intrapelvic), open biopsy or significant traumatic injury to avoid wound healing complications. Minor procedures and percutaneous biopsies or placement of vascular access device 7 days prior to study entry. 5. Patients who have had radiation therapy within 4 weeks prior to start of study treatment. Palliative radiotherapy to bone lesions within 2 weeks prior to study treatment start. 6. History or clinical evidence of central nervous system (CNS) metastases. Subjects who have previously treated CNS metastases (surgery ± radiotherapy, radiosurgery, or gamma knife) and meet all 3 of the following criteria are eligible: o are asymptomatic and o have had no evidence of active CNS metastases for = 3 months prior to enrolment (inactive/controlled CNS metastases are allowed) and o have no requirement for steroids or enzyme-inducing anticonvulsants (e.g. carbamazepine, phenobarbital, phenytoin) 7. Patients in anticipation of the need for major surgical procedure during the course of the study. 8. Patients with a serious non-healing wound, ulcer or bone fracture. 9. Patients with a history of seizure(s) not controlled with standard medical therapy. 10. Patients receiving chronic systemic treatment with corticosteroids (dose of >10 mg/day methylprednisone equivalent) or another immunosuppressive agent. Inhaled and topical steroids are acceptable. 11. Severely impaired lung function with a resting 02-saturation that is 88% or less on room air. 12. Poorly controlled diabetes as defined by fasting serum glucose >2.0 x ULN. 13. Impaired liver function classified as Child-Pugh class A, B, or C. 14. Active (acute or chronic) or uncontrolled infection of bacterial, mycotic or viral genesis. 15. Liver disease such as chronic active hepatitis or chronic persistent hepatitis. 16. Patients with positive history of severely impaired renal function or prior diagnosis of renal failure or proteinuria. 17. Patients with a known history of HIV seropositivity. 18. Patients with active bleeding. 19. Patients who have any severe and/or uncontrolled medical conditions that could affect their participation in the study, e.g. uncontrolled hypertension defined as systolic blood pressure >160 mmHg and/ or diastolic blood pressure >90 mmHg. 20. Patients who have a history of another primary malignancy and of treatment for = 3 years, with the exception of non-melanoma skin cancer and carcinoma in situ of the uterine cervix or breast, and localized cancer of the bladder (T1) or prostate (T1 - T2). 21. Female patients who are pregnant or breast feeding (pregnancy defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mIU/ml)), or adults of reproductive potential who are not using effective birth control methods (Pearl Index <1). If barrier contraceptives are being used, these must be continued throughout the trial by both sexes. Oral contraceptives that do not contain estrogen are acceptable for female patien
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to assess the efficacy of everolimus in patients with metastatic renal cell cancer whose disease progressed on or after prior first-line treatment with sunitinib or pazopanib. Efficacy will be measured by the rate of patients who are free of disease progression after 6 months of treatment with everolimus.;Secondary Objective: The secondary objectives of this study are to gather additional data on the efficacy and safety of everolimus in patients after prior treatment with sunitinib or pazopanib. To this end, the following will be evaluated: ? Estimate the progression-free survival of patients treated with everolimus after having progressed on or after first-line sunitinib or pazopanib therapy ? To assess overall survival of patients treated with everolimus after failure of first-line sunitinib or pazopanib therapy ? To assess overall response rate (ORR) according to RECIST-criteria (version 1.1) after failure of first-line sunitinib or pazopanib therapy ? To assess the duration of response after failure of first-line sunitinib or pazopanib therapy ? To assess the safety profile of everolimus after failure of first-line sunitinib or pazopanib therapy ;Primary end point(s): The primary objective of this study is to evaluate the efficacy of everolimus (Afinitor®) in patients with progressive renal cell carcinoma after failure of first-line sunitinib or pazopanib therapy.;Timepoint(s) of evaluation of this end point: 6 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary efficacy objectives are to evaluate progression-free survival (PFS), overall survival (OS), duration of response (CR/PR) and overall response rate (CR/PR). If not otherwise indicated, secondary efficacy variables will be analyzed for the FAS using radiologic assessments. Frequencies will be reported for proportions together with exact confidence intervals computed according to the Clopper-Pearson method. Time-to-event variables will be analyzed using the Kaplan-Meier method. Kaplan-Meier estimates will be presented together with appropriate confidence intervals. Furthermore, 25%, 50% (median time-to-event) and 75% percentiles will be displayed. The Kaplan-Meier curve will be presented graphically. For convenience, for all secondary efficacy analyses, two-sided 95% confidence intervals will be provided.;Timepoint(s) of evaluation of this end point: 6 months; overall survival after 4 years | — |
Countries
Germany
Contacts
Public ContactProject Leader
Novartis Pharma GmbH
Outcome results
None listed