This is a Phase II open-label study evaluating the preliminary efficacy and safety of bafetinib administered as 240 mg orally twice daily in subjects with Hormone Refractory Prostate Cancer.

Inclusion Criteria:

• Males age ≥18 years.
• Histologically confirmed diagnosis of adenocarcinoma of the prostate.
• Hormone-refractory prostate cancer having progressed despite androgen deprivation therapy that resulted in a castrated level of testosterone (<50 ng/dL) or orchiectomy; with or without evidence of measurable or evaluable disease.
• PSA increase defined as 2 consecutive rises; first increase in PSA occurred a minimum of 1 week from the reference value; increase in PSA should be at least 25% above the reference value and absolute PSA value should be >5 ng/mL.
• May have received no more than 1 prior chemotherapy regimen. Prior immunomodulatory therapy (sipuleucel-t (Provenge), interferon) is allowed.
• Must be taking a single agent LHRH agonist or antagonist, unless previously underwent orchiectomy.
• ECOG performance status 0-2.
• Able to swallow pills.
• Able to provide written, voluntary informed consent, comply with trial procedures, and have accessibility to the site.

Exclusion Criteria:

• Chemotherapy, antibody therapy, major surgery or irradiation within 4 weeks of study enrollment
• Exposure to any investigational agent within 30 days of the Screening Visit.
• No prior flutamide (Eulexin) and ketoconazole use within 4 weeks, bicalutamide (Casodex) within 6 weeks or nilutamide (Nilandron) within 6 weeks of study enrollment.
• Use of Quadramet therapy during 2 months prior to study enrollment or Metastron ever.
• Prior treatment with a tyrosine kinase inhibitor.
• Subjects who have started bisphosphonate therapy within 4 weeks of study enrollment are excluded. Subjects treated with a stable dose of a bisphosphonate for >4 weeks and the tumor has still progressed can be enrolled in the study.
• Known CNS disease or CNS metastases.
• History of other malignancies within the last five years except curatively treated basal cell carcinoma or superficial bladder cancer.
• Laboratory values: Screening serum creatinine greater than or equal to 1.5 x ULN, alanine aminotransferase (ALT) greater than 3 times the upper limit of normal, total bilirubin greater than 3 times the upper limit of normal, white blood cell (WBC) count <3500/mm3, absolute neutrophil count <1500/mm3, hematocrit level <35% and platelets <100,000/mm3.
• History of abnormal bleeding or use of anticoagulant therapy.
• Clinically evident congestive heart failure >class II of the New York Heart Association (NYHA) guidelines.
• Serious, clinically significant cardiac arrhythmias, defined as the existence of an absolute arrhythmia or ventricular arrhythmias classified as Lown III, IV or V.
• History of MI within 6 months or uncontrolled angina within 3 months.
• Severe and/or uncontrolled medical disease (e.g. uncontrolled diabetes, chronic renal disease, chronic liver disease.
• Known HIV infection.
• Uncontrolled active, infection.
• Substance abuse or any condition that might interfere with the subject's participation in the study or in the evaluation of the study results.
• Any condition that in the opinion of the Investigator is unstable and could jeopardize the subject's participation in the study.