Alisertib, Abiraterone Acetate and Prednisone in Treating Patients With Hormone-Resistant Prostate Cancer

Inclusion Criteria

• Age >/= 18 years and are capable of giving informed consent. 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performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
• Patients must have a pathologically confirmed diagnosis of prostate adenocarcinoma. Features of neuroendocrine phenotype are allowed.
• Patients must have evidence of metastatic disease.
• Patients are currently on Abiraterone treatment and the treatment dose has been stable for at least 4 weeks. There will be no further dose adjustment per treating physician.
• Patients with evidence of any of the following disease progression based on PCWG2 criteria while on abiraterone acetate and prednisone:
• Clinical progression (such as symptoms related to prostate cancer) with PSA progression (defined as 25% increase over baseline value with an increase in the absolute value of at least 2 ng/mL and a baseline PSA of 2 ng/ml or above).
• Progression of one dimension measurable soft tissue (nodal or visceral metastasis) assessed within 30 days prior to registration by a CT scan or MRI of the abdomen and pelvis as per RECIST criteria.
• Progression of bone disease (evaluable disease) or ( ≥ 2 new bone lesion(s)) by bone scan.
• Patients must have and ECOG performance status of ≤ 2.
• Patients must be on continuous LH-RH agonist or antagonist treatment or surgically castrated with castrate levels of testosterone ( 1.5 x ULN, calculated or measured creatinine clearance must be ≥ 40 mL/minute (Cockcroft-Gault).
• ANC > 1500/mm³, platelets > 100,000/mm³, Hgb > 9 g/dL. Values must be obtained without need for myeloid growth factor or platelet transfusion support within 14 days, however, erythrocyte growth factor is allowed as per published ASCO guidelines.
• Total bilirubin ≤ ULN, SGOT (AST) and SGPT (ALT) Grade 1 diarrhea, not controlled with appropriate treatment.
• History of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease requiring supplemental oxygen.
• Clinical and/or radiographic evidence of cerebral metastases. However, patients who have a history of central nervous system (CNS) metastasis but who have no radiographic or clinical evidence of residual tumor (eg, following complete surgical resection or stereotactic radiosurgery) are not excluded from participation in this study.
• Radiation therapy to more than 25% of the active bone marrow. Whole pelvic radiation is considered to be over 25%.
• 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.
• Serious medical or psychiatric illness 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.
• Currently active other malignancy excluding controlled non-melanoma skin cancer. Patients are considered NOT to have "currently active" malignancy if they have completed any necessary therapy and are considered by their physician to be at less than 30% risk of relapse.
• 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.
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