This phase II trial studies how well giving abiraterone acetate and prednisone with or without dasatinib works in treating patients with metastatic, hormone-resistant prostate cancer. Androgens can cause the growth of prostate cancer cells. Antihormone therapy, such as abiraterone acetate, may lessen the amount of androgens made by the body. Dasatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether abiraterone acetate and prednisone is more effective than abiraterone acetate, prednisone, and dasatinib in treating prostate cancer

PRIMARY OBJECTIVES:

I. To compare the progression-free survival of men with metastatic castration-resistant prostate cancer treated with abiraterone (abiraterone acetate) plus dasatinib to that of men treated with abiraterone alone.

SECONDARY OBJECTIVES:

I. To describe the toxicity profile of the combination, as well as the rate of prostate-specific antigen (PSA) response, objective responses, and changes in circulating tumor cell (CTC) numbers.

OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM A: Patients receive abiraterone acetate 1000 mg orally (PO) once daily (QD) and prednisone 5 mg PO twice daily (BID) on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive abiraterone acetate and prednisone as patients in arm A. Patients also receive dasatinib 100 mg PO QD on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically.

Inclusion Criteria:

• Metastatic, castration-resistant prostate cancer

  • Defined as evaluable radiographic disease with rising PSA x 2 (at least 1 week apart) or radiographic progression (new soft tissue/bone lesions or enlarging soft tissue lesions) despite medical or surgical castration
  • No limit on prior hormonal therapies (i.e. anti-androgens, ketoconazole) except that subject must not have received abiraterone previously
  • No limit on prior biologic therapies (i.e. immune therapy, antiangiogenic, targeted) except that patient should not have received dasatinib or other v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian) (src)-targeted therapy

• No prior chemotherapy for metastatic disease

  * Subjects who have received chemotherapy in the neoadjuvant or adjuvant setting will be eligible provided chemotherapy was completed > 6 months prior to enrollment

• Eastern Cooperative Oncology Group (ECOG) 0-2

• Total bilirubin =< 1.5 times the institutional upper limit of normal (ULN) except for Gilbert's syndrome

• Hepatic enzymes (aspartate aminotransferase [AST], alanine aminotransferase [ALT] ) =< 2.5 times the institutional ULN

• Serum sodium (Na), potassium (K+), magnesium (Mg+), phosphate and calcium (Ca+) > lower limit of normal (LLN)

• Serum creatinine =< 1.5 time the institutional ULN

• Hemoglobin (Hb) >= 9

• Platelets >= 100,000

• Absolute neutrophil count (ANC) >= 1000

• Ability to take oral medication (study medications must be swallowed whole)

• Men with fathering potential must agree to use contraception throughout study treatment; acceptable methods include: condoms, sponge, intrauterine device (IUD), oral contraceptives

• Concomitant medications * Patient agrees to discontinue St. Johns wort while receiving dasatinib therapy (discontinue St. Johns wort at least 5 days before starting dasatinib)

Exclusion Criteria:

• Known hepatitis B or C or human immunodeficiency virus (HIV), regardless of viral load

  * Testing for the purposes of enrollment is not mandatory, however a documented history of these infections will be exclusionary due to concerns for drug-drug interactions with antivirals and potential for increased risk of liver toxicity

• Radiation for palliation of bony metastases within the preceding 2 weeks

• Prior chemotherapy for metastatic castration-resistant prostate cancer (CRPC)

  * Immune therapy with sipuleucel-T is allowed, provided the last infusion was >= 28 days prior to study therapy and there has been at least one documented PSA value rising after completion of sipuleucel-T therapy or progression of disease on imaging after sipuleucel-T

• Malignancy (aside from prostate cancer) which required radiotherapy or systemic treatment within the past 5 years

  • Superficial bladder cancer treated with intravesical therapy and currently in remission will not be an exclusion
  • Skin cancers will not be an exclusion, except for melanoma with a thickness > 1 mm

• Concurrent medical condition which may increase the risk of toxicity, including:

  • Pleural or pericardial effusion of any grade at the time of study entry

  • Cardiac symptoms; any of the following should be considered for exclusion: ** Uncontrolled angina, congestive heart failure or myocardial infarction (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/f interval on pre-entry electrocardiogram (> 450 msec)
    • Hypokalemia or hypomagnesemia if it cannot be corrected prior to abiraterone administration

• History of significant bleeding disorder unrelated to cancer, including:

  • Diagnosed congenital bleeding disorders (e.g., von Willebrand's disease)
  • Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies)
  • Ongoing or recent (=< 3 months) significant gastrointestinal bleeding

• Prohibited treatments and/or therapies

  • Should not be on any additional anti-cancer therapy except for luteinizing hormone-releasing hormone (LHRH) agonist/antagonist; specifically excluded medications include ketoconazole, estrogens, and anti-androgens

  • 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)

    • Quinidine, procainamide, disopyramide
    • Amiodarone, sotalol, ibutilide, dofetilide
    • Erythromycin, clarithromycin
    • Chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide
    • Cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine

• Prisoners or subjects who are involuntarily incarcerated

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