Sequential Two-agent Assessment in Renal Cell Carcinoma Therapy: The START Trial

The goal of this clinical research study is to compare 6 different 2-drug "sequences" of everolimus, bevacizumab, or pazopanib to learn how they may affect metastatic kidney cancer. For the 2-drug sequence, participants will receive 1 of these drugs and may start taking another of these drugs after that. Researchers will also study the safety of these 2-drug sequences.

The Study Drugs: Everolimus is designed to block the growth of cancer cells, which may cause cancer cells to die. Bevacizumab is designed to block the growth of blood vessels that supply nutrients necessary for tumor growth. This may prevent or slow down the growth of cancer cells. Pazopanib is designed to block a protein that may cause uncontrolled tumor growth. Blocking this protein may prevent cancer from growing and spreading. Study Drug Administration: If you are found to be eligible to take part in this study, you will be randomly assigned (as in the roll of dice) to 1 of 6 groups. There is an equal chance of being assigned to each group. * Group 1 will receive pazopanib, possibly followed by bevacizumab. * Group 2 will receive pazopanib, possibly followed by everolimus. * Group 3 will receive everolimus, possibly followed by bevacizumab. * Group 4 will receive everolimus, possibly followed by pazopanib. * Group 5 will receive bevacizumab, possibly followed by pazopanib. * Group 6 will receive bevacizumab, possibly followed by everolimus. If the disease gets worse while you receive your first assigned drug, you will stop taking the drug. Then if you are not having side effects, you will start taking your second assigned drug 2-4 weeks later. Everolimus is taken by mouth 1 time per day (at about the same time each day). Bevacizumab is given by vein over 30-90 minutes, 1 time every 2 weeks. Pazopanib is taken by mouth 1 time per day (at about the same time each day on an empty stomach). You may be able to receive the bevacizumab doses at your local doctor's office. Ask your study doctor about this. Study Visits: Every week during Weeks 1-4, your blood pressure will be checked (either at home, at the clinic, or by your local doctor) if you are taking pazopanib or bevacizumab. If you are checking your own blood pressure at home, you should keep a log to write down your blood pressure. Bring the log to your next clinic visit. Every 2 weeks, urine will be collected for routine tests if you are receiving bevacizumab. Every 4 weeks: * You will have a physical exam, including measurement of your weight and vital signs. * Your performance status will be recorded. * You will be asked about any drugs you may be taking. * You will be asked about any side effects you may have had. * Blood (about 3 tablespoons) will be drawn for routine tests. If you are receiving everolimus, you will fast (have nothing to eat or drink except water) starting the night before these tests. The doctor will discuss this with you. * Urine will be collected for routine tests if you are receiving everolimus or pazopanib. Every 8 weeks, the following tests and procedures will be performed. If you are receiving the study treatment at your local doctor's office, you must return to MD Anderson for these tests and procedures. * Blood (about 3 teaspoons) will be drawn for routine tests. If you are receiving pazopanib, this blood will also be used to check your thyroid function. * You will have CT scans of the chest and abdomen to check the status of the disease. * You will fill out 5 questionnaires about the quality of your life and about how you are feeling. This should take about 30 minutes. Every year, you will have an MRI of the brain to check the status of the disease. Every year, you will have an ECHO or MUGA scan to check the health of your heart. Anytime the doctor decides it is needed, you will have scans such as a CT scan of the pelvis, an MRI scan of the abdomen or brain, ECHO or MUGA scan, and/or a bone scan. After 1 year, if the disease has not gotten worse, you may have less clinic visits and tests. Length of Participation: You may continue taking a study drug for as long as the doctor thinks it is in your best interest. You will no longer be able to take a study drug if intolerable side effects occur, or if the disease gets worse after you take your second assigned study drug. End-of-Treatment Visit: When you are finished taking the study drug(s): * You will have a physical exam, including measurement of your weight and vital signs. * You will be asked about any drugs you may be taking. * You will be asked about any side effects you may have had. Long-Term Follow-Up: After your End-of-Treatment visit, the study staff will contact you by phone, e-mail, or you will come in for a clinic visit. You will be asked about how you are feeling and any side effects you may have had. Each follow-up will take about 5 minutes. Follow-up will take place every 3 months for the first 2 years, every 6 months for the third year, and 1 time a year after that. The last follow-up will be about 5 years after the last patient is enrolled. This is an investigational study. Everolimus, bevacizumab, and pazopanib are all FDA approved and commercially available for kidney cancer. The investigational part of this study is to find out which order these drugs should be given in. Up to 240 patients will be enrolled in this study. All will be enrolled at MD Anderson.