Aurora A Kinase Inhibitor MLN8237 in Treating Patients With Unresectable Stage III-IV Melanoma

Inclusion Criteria: * Stage IIIc or IV histologically proven melanoma (confirmed by Vanderbilt pathologists), that is not curable by standard surgery, radiation therapy, or chemotherapy. No available effective therapy (i.e.; therapy known to be curative,). Non-biopsied (resected) tumor sites must be measurable for therapy. * Patients on stage 2 of the enrollment must have tumor sites that are easily biopsied and be willing to undergo pre- and post-treatment (around day 8 +/- 3 days) tumor biopsies. * Adequate performance status for the study, ECOG 0-1 * Adequate baseline organ system function, including 1. Absolute neutrophil count (ANC) ≥ 1500 cells/mm3 without growth factor support 2. Hemoglobin ≥ 9.0g/dL (without need for transfusion support within 30 days; growth factor allowed) 3. Platelet count ≥100,000 cells/mm3 without transfusion or growth factor requirement 4. INR\<1.5, 5. Creatinine \< 1.5x institutional upper limit of normal (IULN), and/or an adequate renal function as defined by: Calculated creatinine clearance must be ≥ 40 mL/minute (Cockcroft-Gault). 6. Aspartate and alanine aminotransferase \< 2.5 x institutional upper limit of normal (IULN), bilirubin \< 1.5x IULN * Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study and for 3 months after the completion of the study. Male subject agrees to use an acceptable method for contraception for the duration of the study and for 3 months after the completion of the study * A single regimen of prior chemotherapy for metastatic melanoma is allowed. Patients also may have received other immunotherapy or biologic therapy (including kinase inhibitors, antibodies to checkpoints CTLA4, PD1, PDL1, etc.) for metastatic melanoma and there is a limit of three therapy regimens * No prior Aurora kinase inhibitor * Completed prior chemotherapy a minimum of 4 weeks previously (6 weeks for BCNU and/or mitomycin C), 4 weeks for prior immune therapy, 6 weeks for antibodies to checkpoints CTLA4, PD1, PDL1, etc, and 2 weeks for targeted agents (i.e. inhibitors of MEK, BRAF, Akt, PI3K, mTORC1/2) or localized radiation therapy. All treatment All treatment related toxicity must have resolved to grade 2 or less or to a baseline level as well. * Patients cannot receive concomitant radiation therapy at enrollment. While on protocol limited palliative radiotherapy extending over a small bone marrow field (10%) is allowed. * Patients with brain metastases are allowed only if they are off systemic corticosteroids and stable for a minimum of 8 weeks. * Patients must be 18 years of age or above and voluntary written informed consent must be obtained before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care. * Subject must be able to take oral medication and to maintain a fast as required before and after MLN8237 administration. Exclusion Criteria * Uncontrolled or serious infection * Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant. * Patients with thromboembolic disease cannot be on coumadin, but low molecular heparins are allowed. * Radiation therapy to more than 25% of the bone marrow. Whole pelvic radiation is considered to be over 25%. * Prior allogeneic bone marrow or organ transplantation. * Concurrent therapy for cancer. * Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy. * Inability to comply with protocol-specified procedures (i.e., treatment, monitoring, or follow-up) * Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women. * Patients with GI absorptive problems making it unlikely to absorb study medication or more likely to experience GI toxicities. * Patient is HIV-positive and is receiving combination antiretroviral therapy. * Treatment with clinically significant enzyme inducers, such as the enzyme-inducing antiepileptic drugs phenytoin, carbamazepine or phenobarbital, or rifampin, rifabutin, rifapentine or St. John's wort within 14 days prior to the first dose of MLN8237 and during the study * Other serious medical problem that in the view of the investigator makes therapy difficult to comply with or difficult to interpret toxicity * If applicable, patient has ≥ Grade 2 peripheral neuropathy within 14 days before enrollment. * Serious medical or psychiatric illness likely to interfere with participation in this clinical study. * Patient has received other investigational drugs with 14 days before enrollment