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

You are being asked to take part in this study because you have prostate cancer that has spread to other parts of the body.

This is an investigational study. Prednisone is FDA-approved and commercially available. Abiraterone acetate is FDA-approved and commercially available, but is still being researched. Sunitinib malate is FDA-approved for the treatment of gastrointestinal tumors and renal cell carcinoma, and dasatinib is FDA approved and commercially available for certain types of leukemia. The use of these drugs in prostate cancer and in combination with abiraterone acetate and prednisone is investigational.

Up to 180 patients will be enrolled in this study. All will be enrolled at MD Anderson.

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.

Eligibility Criteria:
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 \</= 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.
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 \</= 1.
10. Hemoglobin \>/= 9.0 g/dL
11. Platelet count \>/= 100,000/microL
12. Serum albumin \>/= 3.5 g/dL
13. Serum creatinine \</= 1.5 x ULN or a calculated creatinine clearance \>/= 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 \</= 1.5 x ULN (except for patients with documented Gilbert's disease) ii. AST or ALT \</= 2.5 x ULN
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 (\</= 3 months) significant gastrointestinal bleeding
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.