A Phase II and Biomarker Study of Tivozanib With Gemcitabine Addition Upon Progression in Patients With Metastatic Refractory Renal Cell Carcinoma

If you agree to participate in this study you will be asked to undergo some screening tests and procedures to confirm that you are eligible. Many of these tests and procedures are likely to be part of regular cancer care and may be done even if it turns out that you do not take part in this study. If you have had some of these tests and procedures recently, they may or may not need to be repeated. The screening process will include the following: medical history, physical examination, measurement of vital signs, performance status assessment, electrocardiogram (EKG), echocardiogram (ECHO), CT or MRI, routine blood tests, urine sample, blood pregnancy test. If these tests show that you are eligible to participate in the research study, you will begin the study treatment. If you do not meet the eligibility criteria, you will not be able to participate in this research study. This study is broken into two segments. In the first segment, you will receive tivozanib alone. Every 28 days in this study is called a study "cycle". You will come to clinic once every 28 days (once a month), on 'day 1' of each 28 day cycle. Tivozanib is a pill that you take by mouth. You will take it once per day, in the morning, with a glass of water, with or without food. You will take tivozanib days 1-21 (the first three weeks) of each 28 day treatment cycle. You will be given a Study Drug Administration Diary to keep a brief record of the date and time when you take your dose of tivozanib. The study staff will explain to you how to complete your diary. This will be reviewed during yur visits by your doctor or a member of the study staff. This diary will be collected at your visit at the end of each cycle, and a new one will be given to you at the start of the next cycle. You will also have a pre-dose research blood draw (approximately 8 teaspoons of blood will be drawn) prior to your first dose of tivozanib, and after your first cycle of tivozanib. Your samples will not have personal information about you (such as your name and address) on them. On Day 1 of every cycle you will have: a medical history, physical exam, measurement of your vital signs, performance status assessment, routine blood tests to monitor your health, urine sample. Every other cycle (prior to cycle 3, 5, 7 etc). you will have a CT or MRI scan, EKG, ECHO. If your cancer gets worse while receiving tivozanib alone you may be eligible to participate in segment 2 of the study and receive tivozanib in combination with gemcitabine. You will come to the clinic on days 1 and 8 of each 28 day cycle. Gemcitabine will be given through a vein (intravenously, or IV) over a period of 30 minutes at the study clinic. This is called an infusion. You will receive the gemcitabine on days 1 and 8 of each treatment cycle. You will also have a pre-dose research blood draw (approximately 8 teaspoons of blood will be drawn) prior to your first cycle of tivozanib and gemcitabine in combination, after your first 28 days cycle of tivozanib and gemcitabine in combination, and if your cancer gets worse while receiving tivozanib and gemcitabine in combination. Your samples will not have personal information about you (such as your name and address) on them. If your doctor determines it is safe for you to have a biopsy, you will undergo a fresh tumor biopsy at the following time points: Prior to receiving your first 28 day cycle of tivozanib and gemcitabine in combination; and after two 28 day cycles (roughly 2 months) of receiving tivozanib and gemcitabine in combination. On Days 1 and 8 and at the end of study treatment you will undergo a medical history, physical examination, measurement of vital signs, performance status assessment, routine blood tests and a urine sample. If an unexpected or unwanted event happens during the study, you may be asked to have some extra tests or measurements. Some of the tests or measurements done during the study may have to be repeated if the results are not usable or are abnormal. If additional visits are required during your participation in this study, your study doctor may perform the following procedures and evaluations: medical history, vital sign measurements, physical exam, ECG, performance status, blood and urine tests and/or a review of your study drug administration diary. We would like to keep track of your medical condition indefinitely. If we do not hear from you, we would like to do this by calling no more than every three months to see how you are doing. Keeping in touch with you and checking your condition helps us look at the long-term effects of the research.