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

Inclusion Criteria

• 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 /= 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 /= 9.0 g/dL
• Platelet count >/= 100,000/microL
• Serum albumin >/= 3.5 g/dL
• Serum creatinine /= 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 /= 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.

Exclusion Criteria

• 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.
• Pathological finding consistent with small cell carcinoma of the prostate
• 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.
• No malignancy [other than the one treated in this study] which required radiotherapy or systemic treatment within the past 5 years.)
• 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)
• 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
• Prolonged QTc interval on pre-entry electrocardiogram (>/= 450 msec)
• Active or symptomatic viral hepatitis or chronic liver disease
• History of pituitary or adrenal dysfunction
• Known brain metastasis
• 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 (