TKI258 in Castrate Resistant Prostate Cancer

Inclusion Criteria

• Histologically proven adenocarcinoma of the prostate with evidence for skeletal metastases on bone scan and/or CT scan.
• Eastern Cooperative Oncology Group (ECOG) performance status /= 50%)
• Serum testosterone levels /= 4 weeks and antiandrogens >/= 6 weeks prior to study drug.
• 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 /= 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 60 mL/min (as calculated by Cockcroft-Gault method) 8) Serum potassium >/= 3.5 mmol/L
• No evidence of chronic or acute DIC (Disseminated Intravascular Coagulation) or bleeding tendency and no angina at rest.
• 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

• Histologic variants other than adenocarcinoma in the primary tumor
• 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
• 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.
• Requirement for corticosteroids greater than the equivalent of 7.5 mg of prednisone daily.
• Therapy with samarium or strontium within 8 weeks prior to first dose of study drug.
• Active infection or concomitant illness that is not controlled with medical management.
• Prior radiation therapy completed 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.
• History of pituitary or adrenal dysfunction
• History of gastrointestinal disorders (medical disorders or extensive surgery) which may interfere with the absorption of the study drug.
• Prior therapy with TKI258
• 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.
• 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.
• 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).