Maximal Androgen Depletion Followed by Randomization of Maximal Androgen Ablation With Molecular Targeted Therapies

Prior treatment

• Radiation therapy for treatment of the primary tumor within 6 weeks of Cycle 1, Day 1. Patients who have received palliative radiation to a single site and recovered are eligible.
• Previously treated with ketoconazole (for prostate cancer) for greater than 7 consecutive days OR previously treated with any other -azole drug (e.g. fluconazole, itraconazole) within 4 weeks of Cycle 1, Day 1
• Prior flutamide (Eulexin) treatment within 4 weeks of Cycle 1, Day 1 (patients whose PSA did not decline for three or more months in response to antiandrogen given as a second line or later intervention will require only a two week washout prior to Cycle 1, Day 1)
• Bicalutamide (Casodex), nilutamide (Nilandron) within 6 weeks of Cycle 1 Day 1 (patients whose PSA did not decline for three or more months in response to antiandrogen given as a second line or later intervention will require only a two week washout prior to Cycle 1, Day 1)
• Administration of an investigational therapy for prostate cancer within 30 days of Cycle 1, Day 1
• Patients taking category I drugs that are generally accepted to have a risk of causing Torsades de Pointes including: (Patients must discontinue drug 7 days prior to starting dasatinib) i) quinidine, procainamide, disopyramide ii) amiodarone, sotalol, ibutilide, dofetilide iii) erythromycin, clarithromycin iv) chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide v) cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine.

Other illness

• Active infection (requiring oral or IV antibiotics) or other medical condition that would make prednisone/prednisolone (corticosteroid) use contraindicated
• Any chronic medical condition requiring a higher dose of corticosteroid than 5mg prednisone/prednisolone twice daily.
• No malignancy \[other than the one treated in this study\] which required radiotherapy or systemic treatment within the past 5 years.)
• Uncontrolled hypertension (systolic BP \>/= 140 mmHg or diastolic BP \>/= 90 mmHg). Patients with a history of hypertension are allowed provided blood pressure is controlled by anti-hypertensive treatment
• Active or symptomatic viral hepatitis or chronic liver disease
• History of pituitary or adrenal dysfunction
• History of significant bleeding disorder unrelated to cancer, including: i) Diagnosed congenital bleeding disorders (e.g., von Willebrand's disease) ii) Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies) iii) Ongoing or recent (\</= 3 months) significant gastrointestinal bleeding
• Atrial fibrillation or other cardiac arrhythmia requiring digitalis
• Other malignancy, except non-melanoma skin cancer, with a \>/= 30% probability of recurrence within 24 months
• Any condition which, in the opinion of the investigator, would preclude participation in this trial.
• Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness.

Lab values

• Prolonged QTc interval on pre-entry electrocardiogram (\>/= 450 msec)
• Clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes), Subjects with hypokalemia or hypomagnesemia if it cannot be corrected prior to dasatinib administration or New York Heart Association (NYHA) Class II-IV heart disease or cardiac ejection fraction measurement of \< 50% at baseline

Other

• Pathological finding consistent with small cell carcinoma of the prostate
• Known brain metastasis
• Clinically significant pleural effusion as determined by the Principal Investigator.
• Prisoners or subjects who are involuntarily incarcerated.

• Willing and able to provide written informed consent
• Male aged 18 years and above
• Histologically or cytologically confirmed adenocarcinoma of the prostate
• Metastatic disease documented by positive bone scan or metastatic lesions other than liver or visceral metastasis on CT or MRI.
• Prostate cancer progression documented by PSA according to PCWG2 or radiographic progression according to modified RECIST criteria
• Surgically or medically castrated, with testosterone levels of \</= 50 ng/dL (\</= 2.0 nM). If the patient is being treated with LHRH agonists (patients who have not undergone orchiectomy), this therapy must have been initiated at least 4 weeks prior to Cycle 1 Day 1 and must be continued throughout the study.
• If the patient received previous anti-androgen therapy, then they have shown progression after withdrawal. Patients who received combined androgen blockade with an anti-androgen must have shown PSA progression after discontinuing the anti-androgen prior to enrollment (\>/= 4 weeks since last flutamide, \>/= 6 weeks since last bicalutamide or nilutamide). If progression is documented prior to this time interval, patients are eligible.
• Previous treatment with docetaxel is allowed. Patients must have recovered from any acute toxicity related to the treatment to be eligible.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of \</= 1.
• Hemoglobin \>/= 9.0 g/dL
• Platelet count \>/= 100,000/microL
• Serum albumin \>/= 3.5 g/dL
• Serum creatinine \</= 1.5 x ULN or a calculated creatinine clearance \>/= 60 mL/min
• Serum potassium \>/= 3.5 mmol/L
• Serum sodium, magnesium, potassium, phosphate, and calcium \>/= LLN (lower limit of normal)
• ANC value \>/= 1,000/mm\^3
• Liver function: i. Serum bilirubin \</= 1.5 x ULN (except for patients with documented Gilbert's disease) ii. AST or ALT \</= 2.5 x ULN
• Able to swallow the study drug whole as a tablet/capsule.
• Patients who have partners of childbearing potential (.e.g. female that has not been surgically sterilized or who are not amenorrheic for \>/= 12 months) must be willing to use a method of birth control with adequate barrier protection as determined to be acceptable by the principal investigator during the study and for 13 weeks after last study drug administration.
• Concomitant Medications (i) Patient agrees to discontinue St. Johns Wort while receiving dasatinib therapy (at least 5 days prior). (ii) Patient agrees that IV bisphosphonates will be withheld for the first 8 weeks of dasatinib therapy due to risk of hypocalcemia; (iii) Patient agrees to discontinue use of drugs primarily metabolized by CYP3A4 enzyme; (iv) Patient agrees to discontinue use of H2 Inhibitors or proton inhibitors prior to dasatinib administration.