The goal of this clinical research study is to learn if a decrease in the levels of prostate specific antigen (PSA) may be linked with the status of prostate cancer that has spread to the bones. Researchers also want to learn how changes in your blood PSA level might affect the rebuilding of healthy bones while you are being treated with TKI258 for prostate cancer.

The Study Drug:

TKI258 is designed to perform several anti-tumor functions, including cutting off the blood supply to tumors. Researchers think this may help slow or stop the growth of prostate cancer.

Study Drug Administration:

If you are found to be eligible to take part in this study, you will take 4 capsules of TKI258 1 time each day for 5 days in a row followed by 2 days of rest (Days 1-5, 8-12, 15-19, and 22-26 of each 28-day study "cycle"). You should take the TKI258 capsules with about 8 ounces of water and at least 1 hour before a meal (breakfast) or at least 2 hours following a meal (breakfast). If you want, you may take the drug with a meal that has fewer than 500 calories and 20 grams of fat.

Study Visits:

Every 28 days makes up 1 study "cycle."

On Day 1 of Cycle 1 and all cycles after that, the following tests and procedures will be performed:

• Your complete medical history will be recorded.
• You will be asked about any drugs or treatments you may be receiving.
• You will be asked about any side effects you may have experienced.
• You will have a physical exam, including measurement of your vital signs and weight.
• Your performance status will be evaluated.
• Blood (about 2 tablespoons) will be collected for routine tests. This blood will also be tested to measure your PSA.
• You will have a triplicate ECG (3 ECGs in a row) before you take the study drug. You will also have 1 ECG about 6 hours after you take the study drug.

On Day 12 (+/- 3 days) of Cycles 1 and 2, and day 26 of Cycle 1 (+/- 3 days) blood (about 1 tablespoon) will be collected for routine tests. Part of the Cycle 2 blood draw will be used to measure the amount of TKI258 in your system. Note that the Day 26 of Cycle 1 visit could end up being scheduled on the same day as the Day 1 of Cycle 2 visit described above.

On Day 1 of Cycle 2 and every odd numbered Cycle after this (Cycles 3, 5, 7and so on), the following tests and procedures will be performed:

• Blood (about 2 teaspoons) will be collected for routine tests.
• Urine will be collected to test for markers relating to your bone.

At the end of every cycle (about Day 26), you will have an ECG.

Every 3 Cycles (about every 12 weeks), the following tests and procedures will be performed:

• Blood (about 1 teaspoon) will be drawn to measure your levels of heart enzymes
• You will have an echocardiogram or MUGA scan like the one you had at the screening visit to check your heart function.

About 7-10 weeks after your first dose of study drug, you will have another bone marrow biopsy and aspiration performed to check the status of the disease and for biomarker testing.

CT and/or bone scans will be performed every 8 weeks for the first 6 months and every 3 months after that to check the status of the disease.

Length of Study:

You may remain on study for as long as you are benefiting. You will be taken off study if intolerable side effects occur or if the disease gets worse.

End-of-Study Visit:

Within 4 weeks after your last dose of the study drug, you will return to the clinic for an end-of-study visit. The following tests and procedures will be performed:

• You will have a physical exam, including measurement of your vital signs, and weight.
• Your performance status will be evaluated.
• You will be asked about any drugs or treatments you may be receiving.
• You will be asked about any side effects you have experienced since you last visit.
• Blood (about 3 tablespoons) and urine will be collected for routine tests. This blood will also be tested to measure certain hormones, heart enzymes, and PSA.
• You will have a chest x-ray, bone scan, and either a computed tomography (CT) or magnetic resonance imaging (MRI) scan of your abdomen and pelvis to check the status of the disease.
• You will have an ECG and either an echocardiogram or a MUGA scan.
• You will have a bone marrow biopsy and aspiration performed to check the status of the disease and for biomarker testing.

Long-Term Follow-up:

Once you are no longer on this study, the research staff will check up on you about every 3 months. This update will consist of a phone call, an e-mail, or a review of your medical and/or other records. You will not have any extra tests, procedures, or study visits. If contacted by phone, the call would only last about 5 minutes.

This is an investigational study. TKI258 is not FDA approved or commercially available. It is being used in this study for research purposes only.

Up to 40 patients will take part in this study. All will be enrolled at MD Anderson.

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 \

From the time of enrollment until 30 days beyond the date of the last study drug administration