Pazopanib or Pemetrexed and Crizotinib in Advanced Cancer

The goal of this clinical research study is to find the highest tolerable dose of the combination of Xalkori (crizotinib) either with Votrient (pazopanib) or Alimta (pemetrexed) or of the combination of 3 study drugs that can be given to patients with advanced cancer. The safety of these drug combinations will also be studied. Crizotinib is designed to block a protein called ALK, which is involved in cancer cell growth and survival. Pazopanib is designed to block the growth of blood vessels that supply nutrients needed for tumor growth. This may prevent or slow the growth of cancer cells. Pemetrexed is designed to block proteins that may cause tumors to grow. This is an investigational study. Crizotinib is FDA approved and commercially available for the treatment of locally advanced or metastatic non-small cell lung cancer. Pazopanib is FDA approved and commercially available for treatment of advanced renal cell carcinoma. Pemetrexed is FDA approved and commercially available for the treatment of non-small cell lung cancer. The combination of crizotinib with pazopanib, crizotinib with pemetrexed, pazopanib with pemetrexed, and giving all 3 drugs together to patients with advanced cancer is investigational. Up to 364 patients will take part in this study. All will be enrolled at MD Anderson.

Study groups: Dose escalation: If you are found to be eligible to take part in this study, your doctor will decide if you will receive one of the following drug combinations: * If you are in Group A, you will receive crizotinib and pazopanib. * If you are in Group B, you will receive crizotinib and pemetrexed. * If you are in Group C, you will receive pazopanib and pemetrexed. * If you are in Group D, you will receive crizotinib, pazopanib, and pemetrexed. Once it is decided which combination you will receive, you will be assigned to a dose level based on when you join the study. Up to 8 dose levels of crizotinib with pazopanib will be tested. Up to 6 dose levels of crizotinib with pemetrexed will be tested. Up to 6 dose levels of pazopanib with pemetrexed will be tested. Up to 8 dose levels of pazopanib with pemetrexed and crizotinib will be tested. Up to 6 participants will be enrolled at each dose level. The first group of participants will receive the lowest dose level. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose combination is found. Dose expansion: Once the highest tolerable dose of each study drug combination is found, up to 14 more participants may be enrolled to further study the safety of each combination of drugs at that dose. Study Drug Administration: Each study cycle is 21 days. Drugs should be taken and/or administered simultaneously. On days of pharmacokinetic testing (if you agree) you should take the drugs at least 1 hour before or 2 hours after a meal. If you are taking crizotinib, you will take it by mouth at the same time every day consistently either with or without food. It should be swallowed whole with a glass of water. You will take the drug every other day, 1 or 2 times a day. You will be told how often to take this drug. If you are taking pazopanib, you will take it by mouth at the same time every day with a glass of water. You should take it at least 1 hour before or 2 hours after a meal. If you receive pemetrexed: * You will receive it by vein on Day 1 of each cycle over about 10 minutes. * The day before your first dose of pemetrexed, you will start taking folic acid to help lower the risk of side effects. Although the study drug is designed to prevent the body from making folic acid that could help cancer grow and spread, some folic acid is needed to prevent side effects in non-cancerous tissue. You will take folic acid by mouth 1 time every day until at least 30 days after you received the last dose of pemetrexed. * The day before your first dose of pemetrexed, you will receive a vitamin B12 injection. You will receive an injection of Vitamin B12 about every 9 weeks after that. Vitamin B12 is given to help reduce the risks of side effects. * You will take dexamethasone by mouth 2 times a day on the day before, the day of, and the day after you receive pemetrexed. Study Visits: At every study visit, you will be asked about any other drugs or herbal supplements you are taking and about any side effects you may have. During Cycles 1 and 2, you will have weekly blood (about 1 tablespoon) collected for routine tests. During Week 1 of Cycles 2 and beyond: * Your medical history will be recorded, including any cancer symptoms. * You will have a physical exam, including measurement of your weight and vital signs. * Your performance status will be recorded. * Blood (about 1 tablespoon) and urine will be collected for routine tests. * If your doctor thinks it is needed, you will have an ECG to check your heart function. Every 6 weeks, or earlier if needed, blood (about 1 tablespoon) will be drawn for tumor marker testing. After about 6 weeks and then every 2-3 cycles after that, you will have a CT scan, x-ray, MRI scan, and/or PET scan to check the status of the disease. It may be done more often if your study doctor thinks it is needed. If you are able to become pregnant, you will have a blood (about 1 teaspoon) or urine pregnancy test every 2 cycles or at any time the study doctor thinks it is needed. Length of Study Participation: You may continue taking the study drugs for as long as the doctor thinks it is in your best interest. You will no longer be able to take the study drugs if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions. Your participation on the study will be over once you have completed the end-of-dosing and/or follow-up visits. End-of-Dosing Visit: Within 30 days after your last dose of study drugs, you will have an end-of-study visit. If you are having side effects at the time of this visit, you may have follow-up for a longer period of time. At this visit, the following tests or procedures may be performed: * Your medical history will be recorded, including any cancer symptoms. * You will be asked if you have had any side effects. * You will have a physical exam, including measurement of your weight and vital signs. * Your performance status will be recorded. * Blood (about 1 tablespoon) and urine will be collected for routine tests. * Blood (about 1 tablespoon) will be drawn for tumor marker testing. * If the doctor thinks it is needed, you will have an x-ray, CT scan, MRI scan, and/or PET/CT scan to check the status of the disease. * If your doctor thinks it is needed, you will have an ECG to check your heart function.