Metastatic renal cell carcinoma MedDRA version: 9.1 Level: LLT Classification code 10050513 Term: Metastatic renal cell carcinoma
Conditions
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written informed consent (informed consent document to be approved by the institution’s Independent Ethics Committee and consent obtained prior to any study-specific procedure) 2. Age =18 years 3. Able to comply with the protocol 4. Subject with histologically and/or cytologically confirmed, mRCC, with majority (>50%) of conventional clear-cell type is mandatory. (Subjects with predominantly papillary or sarcomatoid features, and subjects with chromophobe, oncocytoma, collecting duct tumours, Bellini tumours or transitional cell carcinoma are not allowed). Tumours of mixed histology should be categorised by the predominant cell type. 5. Prior total nephrectomy for primary RCC. Partial nephrectomy is allowed only if the resection margins were clearly negative. 6. At least one measurable or non-measurable lesion (as per RECIST criteria). 7. Eastern Cooperative Oncology Group (ECOG) PS 0-2 (Karnofsky Performance Status (KPS) = 70) 8. Good or intermediate prognosis disease as defined by Motzer score 9. Life expectancy =12 weeks 10. Adequate haematological function: a. Absolute neutrophil count (ANC) =1.5 x 10 9/L AND b. Platelet count =100 x 10 9/L AND c. Haemoglobin =8 g/dL (may be obtained by the use of erythropoietin or transfusion for anaemia) 11. Adequate liver function: a. Total bilirubin 2 weeks at time of enrolment. 14. Female patients should not be pregnant or breast-feeding. Women of child bearing potential (i.e. a woman who is biologically capable of becoming pregnant) must have a negative serum pregnancy test within 7 days prior to enrolment into the study. If a serum pregnancy test is not performed within 7 days prior to the first dose of bevacizumab, a confirmatory urine test (within 7 days prior to the first dose of bevacizumab) is required. Patients (men and women) must agree to use medically accepted contraceptive methods with their partners throughout the study and for 6 months after the last dose of bevacizumab and/or IFN (whichever is administered last). 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: 1. Prior systemic treatment for mRCC disease (including neo-adjuvant therapy) 2. Current or previously treated central nervous system (CNS) metastases or spinal cord compression 3. Major surgery (incl. open biopsy) or radiation therapy within 28 days prior to enrolment. (Palliative radiotherapy to painful bone lesions is not allowed within 14 days prior to enrolment). Subject must have recovered from prior surgery (> 28 days) and radiation (> 28 days - 14 days if palliative radiotherapy to painful bone lesions). 4. Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to enrolment 5. Significant cardiovascular disease defined as congestive heart failure (NYHA Class II, III, or IV – see Appendix 3), unstable angina pectoris, or myocardial infarction within 6 months prior to enrolment. 6. 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 7. History of stroke or transient ischaemic attack within 6 months prior to enrolment 8. Significant vascular disease (e.g., aortic aneurysm, aortic dissection), or symptomatic peripheral vascular disease 9. Evidence or history of recurrent thromboembolism (>1 episode of deep venous thrombosis/peripheral embolism) during the past 2 years, bleeding diathesis or coagulopathy 10. Chronic daily intake of aspirin >325 mg/day or clopidogrel >75 mg/day 11. History of abdominal or tracheo-oesophageal fistula, gastrointestinal perforation, or intraabdominal abscess within 6 months prior to study enrolment 12. Serious, non-healing wound, ulcer, or bone fracture 13. Immuno-compromised patients, including known seropositivity for human immunodeficiency virus (HIV) 14. Chronic treatment with corticosteroids (dose of >10 mg/day methylprednisolone equivalent) excluding inhaled steroids or substitution therapy 15. Known hypersensitivity to any component of the investigational drugs or excipients 16. Current active second malignancy other than non-melanoma skin cancers and post-treatment for localised prostate cancer. Patients are not considered to have a currently active malignancy if they are in complete remission for >3 years prior to study 17. Any other significant medical illness or medically significant abnormal laboratory finding that would, in the investigator’s judgment, make the patient inappropriate for this study, or would increase the risk associated with the patients’ participation in the study. 18. Treatment with any other investigational agent, or participation in another clinical trial within 28 days prior to enrolment. 19. Prior treatment with bevacizumab for any indication
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the PFS and safety of bevacizumab (10 mg/kg i.v. every two weeks) in combination with a low dose of IFN (3 MIU s.c. three times per week) administered until disease progression as first-line treatment of mRCC, and compare these results to the ‘bevacizumab in combination with IFN 9 MIU s.c. three times per week arm’ in the AVOREN trial. Safety comparison is based on the assessment of adverse events of special interest such as fatigue, asthenia, malaise, influenza-like illness and pyrexia.;Secondary Objective: -To assess the efficacy of bevacizumab in combination with IFN 3MIU s.c. three times per week as measured by best ORR (as defined by RECIST criteria) and OS. -To make an historical comparison between ORR and OS of bevacizumab in combination with IFN 3 MIU s.c. t.i.w, and the ORR and OS of bevacizumab in combination with IFN 9 MIU s.c. t.i.w, reported in the AVOREN trial (BO17705, the pivotal study for registration of bevacizumab in mRCC) -To characterise the safety profile of bevacizumab in combination with IFN 3 MIU s.c. t.i.w, administered until disease progression in terms of, Grade 3-5 AE rate, overall AE rate and SAE rate -To make a historical comparison between the safety profile of bevacizumab in combination with IFN obtained in this study and the safety profile of bevacizumab in combination with IFN reported in the AVOREN trial. ;Primary end point(s): The primary endpoint of this study is to assess the rate of PFS and evaluate the safety of bevacizumab in combination with IFN 3 MIU s.c. three times per week until disease progression as first-line treatment of mRCC. | — |
Countries
Czech Republic, Estonia, Finland, Germany, Greece, Italy, Lithuania, Netherlands, Portugal, Sweden, United Kingdom
Outcome results
None listed