Selumetinib and Olaparib in Solid Tumors

Study Groups: If you are found to be eligible to take part in this study, you will be assigned to a phase depending on when you join the study. Up to 30 participants will be enrolled in Phase 1, and up to 60 participants will be enrolled in Phase 2. If you are enrolled in Phase 1, the dose of the study drugs you receive will depend on when you join this study. Up to 3 dose level combinations of selumetinib and olaparib will be tested. The first group of participants will receive the lowest dose level of each study drugs. Each new group will receive a higher dose of either selumetinib or olaparib study drugs than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose combination of the study drugs is found. If you are enrolled in Phase 2, you will receive the highest study drug combination that was tolerated in Phase 1. Study Drug Administration: Each study cycle is 28 days. You will take both selumetinib and olaparib by mouth 2 times each day, about 12 hours apart (1 dose in the morning, 1 dose in the evening). You should fast (have nothing to eat or drink except water) for at least 2 hours before and 1 hour after your dose. If you vomit or miss a dose, you should not retake the dose. Wait and take your next scheduled dose. Depending on the dose level of selumetinib you are receiving, you may only take the study drug on Days 1-5 of each week. The study doctor will tell you how often you should take selumetinib. You will be given a study drug diary to record when you take each dose. The study staff will show you how to fill it out. You will wait to take your morning dose of study drugs at the clinic on certain days. The study staff will remind you before each of these clinic visits. Length of Treatment: You may continue to receive the study drugs for as long as the study doctor thinks it is in your best interest. You will no longer be able to receive the study drugs if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions. Your active participation on the study will be over after the 30-day follow-up visit; however, you will be contacted by phone every 3 months to check on you and the status of the disease. Study Visits: On Days 1 and 15 of Cycle 1: * You will have a physical exam * Blood (about 3 tablespoons) will be drawn for routine and PD testing. * If you are in Phase 1, part of this sample on Day 1 will be used for pharmacokinetic (PK) testing. PK testing measures the amount of study drug in the body at different time points. * If you are in Phase 2, part of this sample will be used for tumor marker testing. * You will have an EKG. * On Day 15, if you are in Phase 2, you will have a tumor biopsy for PD testing, including genetic testing. On Day 8 of Cycle 1: * You will have a physical exam. * Blood (about 3 tablespoons) will be drawn for routine and PD tests. If you are in Phase 2, part of this sample will be used for tumor marker testing. * You will have an EKG. On Day 22 of Cycle 1: * You will have a physical exam. * Blood (about 3 tablespoons) will be drawn for routine and PD tests. If you are in Phase 2 and have endometrial or ovarian cancer, part of this blood will be used for tumor marker testing. On Day 1 of Cycle 2: * You will have a physical exam. * You will have an eye exam. * Blood (about 3 tablespoons) will be drawn for routine and PD tests. * If you are in Phase 1, part of this blood will be used for PK testing. * If you are in Phase 2, part of this blood will be used for tumor marker testing. On Day 26 of Cycle 2, you will have an MRI or a CT scan. On Day 1 of Cycles 3 and beyond: * You will have a physical exam * Blood (about 3 tablespoons) will be drawn for routine and PD tests. If you are in Phase 2, part of this blood will be used for tumor marker testing. Starting on Day 1 of Cycle 4 and every 3 cycles after that, you will have an ECHO. During Cycles 4 and 6 and then every 3 cycles after that (Cycles 9, 12, 15, and so on), you will have MRI or a CT scan. At any time the study doctor thinks it is needed, you may have some or all of these tests repeated to check on your health. End-of-Treatment Visit: Within 7 days after your last dose of study drugs: * You will have a physical exam. * Blood (about 3 tablespoons) will be drawn for routine and PD tests. * If it has been more than 28 days since the last scan, you will have an MRI or CT scan. Follow-Up: About 30 days after your last study drug dose: * You will have a physical exam. * Blood (about 2 tablespoons) will be drawn for routine tests. You may be called by a member of the study staff every 3 months to ask how you are doing and if you have had any side effects. This call should last about 5-10 minutes.