Genomic Guided Therapy With Dasatinib or Nilutamide in Metastatic Castration-Resistant Prostate Cancer

Inclusion Criteria:

1. Confirmed diagnosis of adenocarcinoma of the prostate.
2. Radiographic evidence of metastatic disease amenable to image-guided biopsy.
3. Testosterone \<50ng/dL on androgen deprivation therapy (ADT). ADT must continue while on study.
4. The patient must have discontinued antiandrogens 30 days prior to baseline PSA unless the patient did not respond to anti-androgen therapy or experienced a decline in PSA lasting \< 3 months after starting antiandrogen therapy.
5. Evidence of disease progression on ADT.
6. Patients must have adequate organ and marrow function as defined below:

   * Hemoglobin \>9.0g/dL (without transfusion of PRBC)
   * ANC/AGC \>1,500/μl
   * Platelets \>75,000/μl
   * Total bilirubin \< 2.0 times the institutional ULN
   * Creatinine \<1.5 times the institutional ULN
   * PT or INR and aPTT \< 1.5 times the institutional ULN
   * AST and ALT \<2.5 x ULN
7. Age \> 18 years
8. Ability to take oral medications (pills must be swallowed whole)
9. ECOG performance status 0-2
10. Concomitant Medications:

    * Patient agrees to discontinue and not to initiate taking St. Johns Wort while receiving dasatinib therapy (discontinue St. Johns Wort at least 5 days before starting dasatinib)
    * Patient agrees not to initiate IV bisphosphonates while on dasatinib. Patients on IV bisphosphonates for \> 4 weeks prior to dasatinib will continue on therapy
11. Men of reproductive potential who have not had a radical prostatectomy must agree to use an effective contraceptive method. Patients who have had a prostatectomy are sterile and do not need to use contraception
12. Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

1. Patients who have received prior treatment with nilutamide or dasatinib
2. Patients who have not recovered to Grade 1 or Grade 0 from the toxic effects of prior investigational therapy, biologic therapy, hormonal therapy (other than ADT), immunotherapy, or chemotherapy
3. Medical contraindications to stopping aspirin or coumadin for 1 week prior to image-guided tumor biopsy AND while on dasatinib treatment.
4. History of the following cardiac related conditions:

   * Uncontrolled angina, congestive heart failure or MI within (6 months)
   * Diagnosed congenital long QT syndrome
   * Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes)
   * Prolonged QTc interval on pre-entry electrocardiogram (\> 450 msec)
   * Subjects with hypokalemia or hypomagnesemia if it cannot be corrected prior to dasatinib administration
5. History of significant bleeding disorder unrelated to cancer.
6. Concomitant use of Category I drugs that are generally accepted to have a risk of causing Torsades de Pointes including: (These medications can be stopped while the patient is on the protocol and the patient needs to be off the drugs for at least 7 days prior to starting dasatinib)
7. Patients who have a history of amiodarone use.
8. Clinically significant pericardial or pleural effusion or severe respiratory insufficiency
9. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (requiring antifungal, antibiotic or antiviral therapy), symptomatic congestive heart failure (NYHC II or greater, unstable angina pectoris, cardiac arrhythmia (uncontrolled SVT or any VT), or psychiatric illness/social situations that would limit compliance with study requirements.
10. Patients with a medical contraindication to image-guided biopsies