Abiraterone Acetate and Prednisone With or Without Dasatinib in Treating Patients With Metastatic Hormone-Resistant Prostate Cancer

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