Metastatic Renal Cell Carcinoma MedDRA version: 9.1 Level: LLT Classification code 10050513 Term: Metastatic renal cell carcinoma
Conditions
Sponsors
GlaxoSmithKline Research & Development Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Part I 1. Histologically or cytologically confirmed unresectable RCC with a clear cell component. 2. Experienced documented evidence of radiological progression based on [RECIST] while on first line (or greater) RCC therapy and within 6 months prior to the first dose of study medication (bevacizumab). 3. Evidence of unidimensionally measurable disease. 4. Free of any malignant disease other than RCC for at least 5 years prior to the first dose of (bevacizumab) in this study, with the exception of the following: Cervical carcinoma in situ, Melanoma in situ,Basal or squamous cell carcinoma of the skin 5. ECOG Performance Status of 0 to 1. 6. Resolution of all acute toxic effects of prior chemotherapy, radiotherapy, or surgical procedures to NCI CTCAE Grade 1 or less. 7. Adequate organ function, as defined by the protocol. 8. Males and females = 18 years of age at screening. Part II 1. The subject met all eligibility criteria in Part I of the study. 2. The subject would derive continued therapeutic benefit from anti-angiogenic therapy. 3. There are no safety concerns that would present an unacceptable benefit-risk profile for treatment with pazopanib. 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. Cancer metastatic to the central nervous system or leptomeningeal carcinomatosis. 2. Previous treatment with bevacizumab or pazopanib. 3. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to bevacizumab or pazopanib or components of bevacizumab or pazopanib (other than active drugs). 4. Anticancer therapy (radiotherapy, chemotherapy, or immunotherapy) within 28 days prior to the first dose of study medication and through completion of all study procedures. 5. Use of an investigational agent within 28 days or 5 half-lives, whichever is longer, prior to the first dose of study medication. 6. Assessable disease is unsuitable for biopsy or the patient is unwilling or not sufficiently fit to undergo serial biopsies. 7. Major surgical procedure or traumatic injury within 28 days prior to the first dose of study medication (bevacizumab). 8. Evidence of active bleeding or bleeding diathesis, or any serious, non-healing wound, ulcer, or bone fracture. 9. Hemoptysis within 6 weeks of the first dose of study medication. 10. Use of therapeutic doses of warfarin within 5 half-lives of the first dose of study medication and during treatment in the study 11. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 hemorrhage within 28 days of the first dose of study medication. 12. Clinically significant gastrointestinal abnormalities. 13. Known endobronchial lesions or involvement of large pulmonary vessels by tumor. 14. Active or uncontrolled infection at the time of first dose of study medication. 15. Prolongation of corrected QT interval (QTc) >480 milliseconds (msec). 16. Positive test result for (HIV) antibody. 17. Any of the following within 6 months prior to the first dose of study medication (bevacizumab): Cardiac angioplasty or stenting, Severe and/or unstable angina, Myocardial infarction, Coronary artery bypass graft (CABG), Class III or IV congestive heart failure, Symptomatic peripheral vascular disease, Cardiac dysrhythmias of NCI CTCAE Grade 2 or greater and atrial fibrillation of any grade. 18. History of cerebrovascular accident or transient ischemic attack 19. Poorly controlled hypertension. 20. History of pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months. 21. Internal metal medical devices or other metal items that may place the subject's health at risk and/or interfere with MRI scans. 22. History of hypersensitivity to gadolinium or other intravenous dye contrast agents. 23. History of hypersensitivity to iodine-based contrast agents or history of severe asthma. 24. Pregnant or lactating females. 25. Any serious and/or unstable pre-existing medical, psychiatric, or other condition.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To estimate the pharmacodynamic effect of bevacizumab (10mg/kg q2w) on various tumour characteristics in subjects with renal cell carcinoma who experience tumour progression on previous first-line (or greater) therapy.;Secondary Objective: To compare the pharmacodynamic effects of repeat-dose bevacizumab (10mg/kg q2w) versus repeat-dose pazopanib (800 mg qd) in subjects with renal cell carcinoma who experience tumour progression on previous first-line (or greater) therapy. To evaluate the safety and tolerability of repeat-dose bevacizumab (10mg/kg q2w) in subjects with renal cell carcinoma who experience tumour progression on previous first-line (or greater) therapy. To evaluate the safety and tolerability of repeat-dose pazopanib (200mg twice weekly to 1200 mg qd) in subjects with renal cell carcinoma who experience tumour progression on previous first-line (or greater) therapy. ;Primary end point(s): Primary pharmacodynamic endpoints for bevacizumab in Part I will include the following, as data permit: 1. Tumour size, as measured by the sum of the longest diameters of all target lesions on CT and expressed as a percent reduction from baseline. 2. Tumour perfusion, as assessed by the estimation of Ktrans by DCE-MRI. | — |
Countries
United Kingdom
Outcome results
None listed