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

The Study Drugs:

Abiraterone acetate is designed to block male hormones in the body that may cause prostate
cancer to grow.

Prednisone is commonly given in combination with other drugs to patients with prostate
cancer. In this study, it is being used in combination with abiraterone acetate in order to
help prevent side effects that abiraterone acetate may cause.

Sunitinib malate is designed to block pathways that control important events such as the
growth of blood vessels that are essential for the growth of cancer.

Dasatinib is designed to change the function of genes. By changing the function of these
genes, it may prevent cancer from growing and spreading.

Study Drug Administration:

If you are found to be eligible to take part in this study, you will take 4 tablets of
abiraterone acetate by mouth every day. The tablets should be taken all at once, at least 1
hour before a meal or 2 hours after a meal. You will also take 1 tablet of prednisone by
mouth 2 times each day. You will take both of these drugs throughout the entire study.

If the disease gets worse while you are taking abiraterone acetate and prednisone, you will
be randomly assigned (as in the flip of a coin) to 1 of 2 study groups.

- If you are assigned to Group 1, you will start taking sunitinib malate. You will take 3
capsules by mouth 1 time each day, while continuing to take abiraterone acetate and
prednisone.

- If you are assigned to Group 2, you will start taking dasatinib. You will take 2 tablets
by mouth 1 time each day, while continuing to take abiraterone acetate and prednisone.
Dasatinib tablets should be swallowed whole, with or without a meal. If you accidentally
miss taking a dose of dasatinib, it may be taken within 12 hours later. If you vomit
within 30 minutes of taking the tablets, that dose may be repeated. If you miss a dose
due to side effects, the dose should not be replaced.

If the disease gets worse after you have been assigned to a group, and you are still eligible
to continue taking the study drugs, you will "crossover" to the other group. If you were in
Group 1, you would stop taking sunitinib malate and begin taking dasatinib. If you were in
Group 2, you would stop taking dasatinib and begin taking sunitinib malate. No matter which
group you crossover to, you will continue taking abiraterone acetate and prednisone.

Study Visits:

At each study visit, you will be asked about any other drugs you may be receiving and about
any side effects you may be having.

Every 2 weeks during the first 12 weeks of taking abiraterone acetate and prednisone and
during the first 3 cycles (9-12 weeks) of each new treatment combination, blood (about 1-2
tablespoons) will be collected to test your liver function.

Every 4 weeks, the following tests and procedures will be performed:

- You will have a physical exam, including measurement of your vital signs and weight.

- Blood (about 1-2 tablespoons) and urine will be collected for routine tests. Part of
this blood will be used to measure your PSA and your levels of a specific marker of
prostate cancer.

- You will be asked questions about how you are feeling and about any side effects you may
have had since your last visit.

- You will be asked about any other drugs you may be taking.

- Your performance status will be recorded.

If the disease gets worse (or you change treatments) at any point in the study, the following
tests and procedures will be performed:

- Blood (about 1-2 tablespoons) and urine will be collected for routine tests.

- You will have a bone marrow aspiration and biopsy or a tumor tissue biopsy to collect
tumor tissue from places to which the tumor has spread to check the status of the
disease.

- You will have an ECG and an echocardiogram or a MUGA scan.

- You will have a chest x-ray, CT scans of your abdomen and pelvis, and a bone scan to
check the status of your disease.

If your doctor thinks it is necessary:

°You will have a chest x-ray, CT scans of your abdomen and pelvis, and a bone scan to check
the status of your disease.

Length of Study:

You may continue taking the study drugs for as long as the doctor thinks it is in your best
interest. You will be taken off study if the disease gets worse after crossover, if you
experience intolerable side effects, or if the doctor thinks that it is in your best
interest.

End of Treatment Visit:

After you stop receiving the study drugs for any reason, the following tests and procedures
will be performed:

- You will have a physical exam, including measurement of your vital signs and weight.

- Blood (about 1-2 tablespoons) will be drawn for routine tests and to check your PSA
level, your level of a specific marker of prostate cancer, and to check for a protein
related to cancer.

- You will be asked questions about how you are feeling and about any side effects you may
have had since your last visit.

- You will be asked about any other drugs you may be taking.

- Your performance status will be recorded.

- You will have a bone marrow aspiration and biopsy or a tumor tissue biopsy to collect
tumor tissue from places to which the tumor has spread to check the status of the
disease.

Post-Treatment (Safety) Follow-Up Visit:

About 30 days after your last dose of study drugs, the following tests and procedures will be
performed:

- You will have a physical exam, including a measurement of your vital signs.

- Blood (about 1-2 teaspoons) will be drawn for routine tests.

- Your performance status will be recorded.

- You will be asked about any side effects you may have experienced since your last visit.

- You will be asked about any other drugs you may be taking.

Long-Term Follow-Up:

A member of the study staff will check up on you about every 6 months after your
Post-Treatment (Safety) Follow-Up Visit. This will consist of a phone call, an e-mail, or a
review of your medical and/or other records. If you are contacted by phone, the call will
only last a few minutes.

After your End-of-Treatment visit, the study staff will contact you by phone, e-mail, or you
will come in for a clinic visit. You will be asked about how you are feeling and any side
effects you may have had. Each follow-up will take about 5 minutes. Follow-up will take place
every 3 months for the first 2 years, every 6 months for the third year, and 1 time a year
after that. The last follow-up will be about 5 years after the last patient is enrolled.

Inclusion Criteria:

1. Willing and able to provide written informed consent

2. Male aged 18 years and above

3. Histologically or cytologically confirmed adenocarcinoma of the prostate

4. Metastatic disease documented by positive bone scan or metastatic lesions other than
liver or visceral metastasis on CT or MRI.

5. Prostate cancer progression documented by PSA according to PCWG2 or radiographic
progression according to modified RECIST criteria

6. Surgically or medically castrated, with testosterone levels of 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.

7. 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.

8. Previous treatment with docetaxel is allowed. Patients must have recovered from any
acute toxicity related to the treatment to be eligible.

9. Eastern Cooperative Oncology Group (ECOG) Performance Status of
10. Hemoglobin >/= 9.0 g/dL

11. Platelet count >/= 100,000/microL

12. Serum albumin >/= 3.5 g/dL

13. Serum creatinine /= 60 mL/min

14. Serum potassium >/= 3.5 mmol/L

15. Serum sodium, magnesium, potassium, phosphate, and calcium >/= LLN (lower limit of
normal)

16. ANC value >/= 1,000/mm^3

17. Liver function: i. Serum bilirubin Gilbert's disease) ii. AST or ALT
18. Able to swallow the study drug whole as a tablet/capsule.

19. 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.

20. 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:

1. Active infection (requiring oral or IV antibiotics) or other medical condition that
would make prednisone/prednisolone (corticosteroid) use contraindicated

2. Any chronic medical condition requiring a higher dose of corticosteroid than 5mg
prednisone/prednisolone twice daily.

3. Pathological finding consistent with small cell carcinoma of the prostate

4. 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.

5. No malignancy [other than the one treated in this study] which required radiotherapy
or systemic treatment within the past 5 years.)

6. 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

7. 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)

8. 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)

9. 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

10. Prolonged QTc interval on pre-entry electrocardiogram (>/= 450 msec)

11. Active or symptomatic viral hepatitis or chronic liver disease

12. History of pituitary or adrenal dysfunction

13. Known brain metastasis

14. 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

15. 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 (
16. Atrial fibrillation or other cardiac arrhythmia requiring digitalis

17. Other malignancy, except non-melanoma skin cancer, with a >/= 30% probability of
recurrence within 24 months

18. Clinically significant pleural effusion as determined by the Principal Investigator.

19. Administration of an investigational therapy for prostate cancer within 30 days of
Cycle 1, Day 1

20. Any condition which, in the opinion of the investigator, would preclude participation
in this trial.

21. 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.

22. Prisoners or subjects who are involuntarily incarcerated.

23. Subjects who are compulsorily detained for treatment of either a psychiatric or
physical (eg, infectious disease) illness.