Primary Objective:

• To estimate overall survival and early response as characterized by a drop in prostate specific antigen (PSA).
• To identify the PSA modulation in 40 selected patients with advanced prostate cancer and to correlate those findings with changes in bone remodeling markers.

Secondary Objectives:

• To explore the potential association between serum PSA and bone turnover markers with bone marrow fibroblast growth factor receptor 1 (FGF R 1) and fibroblast growth factor 9 (FGF9) while on TKI 258.
• To explore the predictive values of baseline FGF R 1, FGF9, and FGF signaling in serum and those in the bone marrow before and during treatment with TKI258.
• To collect and archive bone marrow biopsies and aspirates, serum and plasma in study patients for later hypothesis generating associations.
• To explore FGF R expression following eight weeks of TKI 258.

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.

Screening Tests:

Signing this consent form does not mean that you will be able to take part in this study. You will have "screening tests" to help the doctor decide if you are eligible to take part in this study. The following tests and procedures will be performed within 30 days before you begin taking the study drug:

• 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 electrocardiogram (ECG -- a test that measures the electrical activity of the heart) and an echocardiogram or multiple gated acquisition (MUGA) scan (heart function tests).

The following tests and procedures will be performed within 14 days before you begin taking the study drug:

• Your complete medical history will be recorded.
• You will have a physical exam, including measurement of your vital signs (blood pressure and pulse), height, and weight.
• You will be asked how well you are able to perform the normal activities of daily living (performance status).
• You will be asked about any drugs or treatments you may be receiving.
• Blood (about 3 tablespoons) and urine will be collected for routine tests. This blood will also be tested to measure your levels of cholesterol, certain hormones, and PSA.
• You will have a bone marrow aspiration and biopsy performed. To collect a bone marrow aspirate/biopsy, an area of the hip is numbed with anesthetic, and a small amount of bone marrow and bone is withdrawn through a large needle. Part of the marrow sample will be used for biomarker testing. Biomarkers are chemical "markers" in the tissue that may be related to your response to the study drug.

The study doctor will discuss the screening test results with you. If the screening tests show that you are not eligible to take part in the study, you will not be enrolled. Other treatment options will be discussed with you.

Study Drug Administration:

If you are found to be eligible to take part in this study, you will take 2 capsules of TKI258 2 times each day (4 total capsules each day) while you are on study.

Study Visits:

Every 28 days makes up 1 study "cycle."

On Day 1 of Cycles 1, 2, and every evenly numbered Cycle after this (Cycles 4, 6, and so on), 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) and urine will be collected for routine tests. This blood will also be tested to measure your PSA and cholesterol levels.

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 whenever the study doctor thinks they are needed 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 your levels of cholesterol, certain hormones, 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.
• 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 M. D. Anderson.

Inclusion Criteria:

1. Histologically proven adenocarcinoma of the prostate with tumor infiltration to the bone as seen on positive bone marrow biopsy and aspirate.
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. Presence of metastatic bone disease
7. Discontinue diethylstilbestrol (DES) or steroids treatment for >/= 4 weeks and for antiandrogens >/= 6 weeks
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) Hemoglobin >/= 8.0 g/dL independent of transfusion; 3) Platelet count >/= 75,000/microL; 4) Serum albumin >/= 3.0 g/dL; 5) Serum creatinine < 1.5 x ULN or a calculated creatinine clearance > 60 mL/min (as calculated by Cockroft-Gault method) 6) 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 x ULN b) AST and ALT >/= 2.5 x ULN, (for patients with known liver metastasis, AST and ALT </= 5 x ULN is allowed)
3. Therapy with other hormonal therapy, including any dose of megestrol acetate (Megace), Ketoconazole, finasteride (Proscar), dutasteride (Avodart) any herbal product known to decrease PSA levels (eg, Saw Palmetto and PC-SPES), or any systemic corticosteroid within 4 weeks prior to first dose of study drug.
4. Active infection or intercurrent illness that are not controlled
5. Unstable angina, myocardial infarction within the previous 6 months, or use of ongoing maintenance therapy for life-threatening ventricular arrhythmia, uncontrolled hypertension (blood pressure >140/90 mm Hg despite optimal medical therapy), New York Heart Association (NYHA) Class III or IV Congestive Heart Failure.
6. Prior radiation therapy completed < 4 weeks or single fraction of palliative radiotherapy within 14 days prior to first dose of study drug.
7. 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.
8. Active psychiatric illnesses/social situations that would limit compliance with protocol requirements.
9. Active or uncontrolled autoimmune disease that may require corticosteroid therapy during study
10. Severely compromised immunological state, including being positive for the human immunodeficiency virus (HIV)
11. Acute or chronic hepatitis B or C
12. Chemotherapy and other investigational therapies (targeted or immunotherapy) will require a 4-week washout period before treatment initiation
13. 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.
14. Long QT syndrome or bundle branch block or hemiblock or other history of life-threatening arrhythmia (unless the patient has been effectively treated for it and is considered stable). Participation in the study of patients with known nonpathologic right bundle branch block is at the discretion of the Principal Investigator.
15. Known brain metastasis
16. History of pituitary or adrenal dysfunction
17. History of gastrointestinal disorders (medical disorders or extensive surgery) which may interfere with the absorption of the study drug.
18. Prior therapy with TKI258
19. 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) grade of </= 1. Chemotherapy induced alopecia and grade 2 neuropathy is allowed.
20. 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.