Phase II Trial of Alisertib (MLN8237) in Salvage Malignant Mesothelioma

Inclusion Criteria: 1. Voluntary written informed consent 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performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care. 2. Female subject is either: post-menopausal for at least one year before the screening visit, or surgically sterilized, or willing to use an acceptable method of birth control (ie, a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study and at least 1 month after the last dose of alisertib. 3. Male subject, even if surgically sterilized (ie, status postvasectomy), agrees to use an acceptable barrier method for contraception (condom with a spermicidal agent), or completely abstain from heterosexual intercourse during the entire study treatment period through 4 months after the last dose of alisertib. 4. Absolute neutrophil count (ANC) \> 1500/mm3, platelets \> 100,000/mm3, Hgb \> 9 g/dL. 5. Total bilirubin \</= 1.5 x upper limit of normal (ULN), SGOT (AST) and SGPT (ALT)\< 2.5 x ULN. AST and/or ALT may be up to 5X ULN if with known liver mets 6. Adequate renal function as defined by: Calculated creatinine clearance must be \>/= 30 mL/minute 7. Eastern Cooperative Oncology Group (ECOG) performance status 0-2 8. Pathologic diagnosis of malignant mesothelioma (any primary site is acceptable) 9. Have unresectable malignant mesothelioma (any histology) 10. Received at least one prior pemetrexed-based chemotherapy for unresectable disease, unless within 3 months of receiving platinum-pemetrexed therapy for neoadjuvant or adjuvant treatment that has been unsuccessful. 11. Up to 4 prior lines of systemic therapy (biologic or chemotherapy) are allowed. Maintenance therapy after 4-6 cycles of front-line chemotherapy is still considered 1 line of therapy and is not considered 2 separate therapies. 12. Patients must have measurable disease by modified RECIST or RECIST. Examinations for assessment of measurable disease must have been completed within 28 days prior to registration. 13. Patient must be \>/= 18 years of age Exclusion Criteria: 1. Radiation therapy to more than 25% of the bone marrow. Whole pelvic radiation is considered to be over 25%. 2. Prior allogeneic bone marrow or organ transplantation 3. Known GI disease or GI procedures that could interfere with the oral absorption or tolerance of alisertib. Examples include, but are not limited to partial gastrectomy, history of small intestine surgery with significant removal of the small intestine, and celiac disease 4. Known history of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease. Patients who use CPAP or BIPAP at night and have controlled sleep apnea syndrome are allowed. 5. Requirement for constant administration of proton pump inhibitor, H2 antagonist, or pancreatic enzymes. Intermittent uses of antacids or H2 antagonists are allowed. 6. Systemic infection requiring IV antibiotic therapy within 14 days preceding the first dose of study drug, or other severe infection. 7. 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. 8. Female subject who is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum Beta-human chorionic gonadotropin (Beta-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women. 9. Patient has received other investigational drugs with 14 days before enrollment 10. Serious medical or psychiatric illness likely to interfere with participation in this clinical study. 11. Other severe acute or chronic medical or psychiatric condition, including uncontrolled diabetes, malabsorption, resection of the pancreas or upper small bowel, requirement for pancreatic enzymes, any condition that would modify small bowel absorption of oral medications, or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for enrollment in this study. 12. 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. 13. 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 alisertib and during the study. 14. Known history of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C. Testing is not required in the absence of clinical findings or suspicion. For guidance in defining active infection for hepatitis B, please refer to the WHO guidelines 15. Prior administration of an Aurora A kinase-targeted agent, including alisertib 16. Receipt of corticosteroids within 7 days prior to the first dose of study treatment, unless patient has been taking a continuous dose of no more than 15 mg/day of prednisone for at least 1 month prior to first dose of study treatment. Low dose steroid use for the control of nausea and vomiting will be allowed. Topical steroid use is permitted. Inhaled steroids are permitted. 17. Inability to swallow oral medication or inability or unwillingness to comply with the administration requirements related to alisertib. 18. Administration of myeloid growth factors or platelet transfusion within 14 days prior to the first dose of study treatment. 19. Persons who are incarcerated at time of enrollment (e.g., prisoners) or likely to become incarcerated during the study.