TKI258 in Castrate Resistant Prostate Cancer

Inclusion Criteria: 1. Histologically proven adenocarcinoma of the prostate with evidence for skeletal metastases on bone scan and/or CT scan. 2. Eastern Cooperative Oncology Group (ECOG) performance status \</= 2. (Karnofsky Performance Status \>/= 50%) 3. Serum testosterone levels \</= 50ng/ml 4. Ongoing gonadal androgen deprivation therapy with luteinizing hormone-releasing hormone (LHRH) analogues or orchiectomy. Patients, who have not had an orchiectomy, must be maintained on standard dosing of LHRH analogue therapy at appropriate frequency for the duration of the study. 5. Progression of disease despite androgen ablation (either documented osseous or soft tissue metastatic disease progression or by PSA criteria progression). a)Definition of Progressive disease by PSA evidence: a PSA level of at least 5 ng/ml which has risen on at least 2 successive occasions, at least 2 weeks apart. The participant will need a baseline test and a test to show that the PSA has increased. 6. Discontinue diethylstilbestrol (DES) for \>/= 4 weeks and antiandrogens \>/= 6 weeks prior to study drug. 7. Discontinue any steroids prescribed to specifically treat prostate cancer (for e.g as a secondary hormonal manipulation or for cord compression) \>/= 4 weeks prior to study drug. Steroids chronically prescribed for a non-cancer-related illness (e.g. asthma or COPD) that is well controlled with medical management are permissible to an equivalent of \< 10 mg Prednisone daily. 8. Antiandrogen Withdrawal: Patients who are receiving an antiandrogen as part of primary androgen ablation must demonstrate disease progression following discontinuation of antiandrogen. Disease progression after antiandrogen withdrawal is defined as 2 consecutive rising PSA values, obtained at least 2 weeks apart, or documented osseous or soft tissue progression. 9. For patients receiving flutamide, at least one of the PSA values must be obtained 4 weeks or more after flutamide discontinuation. 10. For patients receiving bicalutamide or nilutamide, at least one of the PSA values must be obtained 6 weeks or more after antiandrogen discontinuation 11. Laboratory Requirements: 1) Adequate adrenal function (absence of symptoms or electrolyte imbalances that indicate adrenal insufficiency); 2) White blood cell count (WBC) count \>/= 3,000/microl; 3) Absolute Neutrophil Count (ANC) \>/= 1,500/microl; 4) Hemoglobin \>/= 8.0 g/dL independent of transfusion; 5) Platelet count \>/= 75,000/microL; 6) Serum albumin \>/= 3.0 g/dL; 7) Serum creatinine \< 1.5 x ULN or a calculated creatinine clearance \> 60 mL/min (as calculated by Cockcroft-Gault method) 8) Serum potassium \>/= 3.5 mmol/L 12. No evidence of chronic or acute DIC (Disseminated Intravascular Coagulation) or bleeding tendency and no angina at rest. 13. Patient must be willing and able to comply with protocol requirements. All patients must sign an informed consent indicating that they are aware of the investigational nature of this study. Patients must also have signed an authorization for the release of their protected health information. Exclusion Criteria: 1. Histologic variants other than adenocarcinoma in the primary tumor 2. Abnormal liver functions consisting of any of the following: a) Serum bilirubin \>/= 1.5 \* upper limit of normal (ULN) b) AST and ALT \> 2.5 \* ULN 3. Therapy with other hormonal therapy, including any dose of Ketoconazole, finasteride (Proscar), dutasteride (Avodart) any herbal product known to decrease PSA levels (eg, Saw Palmetto and PC-SPES) within 4 weeks of study drug. 4. Requirement for corticosteroids greater than the equivalent of 7.5 mg of prednisone daily. 5. Therapy with samarium or strontium within 8 weeks prior to first dose of study drug. 6. Active infection or concomitant illness that is not controlled with medical management. 7. Prior radiation therapy completed \< 4 weeks or single fraction of palliative radiotherapy within 14 days prior to first dose of study drug. 8. Any currently active second malignancy, other than non-melanoma skin cancer. Patients are not considered to have a currently active malignancy, if they have completed therapy and are considered by their physician to be at least less than 30% risk of relapse over next 3 months. 9. Active psychiatric illnesses/social situations that would limit compliance with protocol requirements. 10. Active or uncontrolled autoimmune disease that may require corticosteroid therapy during study 11. Severely compromised immunological state, including being positive for the human immunodeficiency virus (HIV) 12. Acute or chronic hepatitis B or C 13. Chemotherapy and other investigational therapies (targeted or immunotherapy) will require a 4-week washout period before treatment initiation 14. Initiation of bisphosphonate therapy within 4 weeks prior to first dose of study drug. Patients on stable doses of bisphosphonates that show subsequent tumor progression may continue on this medication; however, patients are not allowed to initiate bisphosphonate therapy during the study. 15. Impaired cardiac function or clinically significant cardiac diseases, including any of the following: a.) History or presence of serious uncontrolled ventricular arrhythmias or presence of atrial fibrillation; b.) Clinically significant resting bradycardia (\< 50 beats per minute); c.) Left ventricular ejection fraction (LVEF) assessed by 2-D echocardiogram (ECHO) \< 50% or lower limit of normal (whichever is higher) or multiple gated acquisition scan (MUGA) \< 45% or lower limit of normal (whichever is higher); 16. (# 13 Conti'd) Any of the following within 6 months prior to study entry: myocardial infarction (MI), severe/unstable angina, Coronary Artery Bypass Graft (CABG), Congestive Heart Failure (CHF), Cerebrovascular Accident (CVA), Transient Ischemic Attack (TIA), Pulmonary Embolism (PE); e.) Uncontrolled hypertension defined by an SBP\>150 and/or a DBP\>100 mm Hg with or without anti-hypertensive medication; f.) Previous pericarditis; clinically significant pleural effusion in the previous 12 months or current ascites requiring 2 or more interventions per month. 17. History of pituitary or adrenal dysfunction 18. History of gastrointestinal disorders (medical disorders or extensive surgery) which may interfere with the absorption of the study drug. 19. Prior therapy with TKI258 20. Any acute toxicities due to prior chemotherapy and/or radiotherapy that have not resolved to a National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) (version 3.0) grade of \</= 1. Chemotherapy induced alopecia and grade 2 neuropathy is allowed. 21. Condition or situation which, in the investigator's opinion, may put the patient at significant risk, may confound the study results, or may interfere significantly with the patient's participation in the study. 22. Men whose partner is a woman of child-bearing potential, (i.e. biologically able to conceive), and who is not employing two forms of highly effective contraception. Highly effective contraception (e.g. male condom with spermicide, diaphragm with spermicide, intra-uterine device) must be used by both sexes during the study and must be continued for 8 weeks after the end of study treatment. Oral, implantable, or injectable contraceptives may be affected by cytochrome P450 interactions, and are therefore not considered effective for this study. Women of child-bearing potential is defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (e.g., who has had menses any time in the preceding 12 consecutive months).