A Phase I/II Study of Azacitidine, Docetaxel, and Prednisone for Metastatic Prostate Cancer Patients

INCLUSION CRITERIA:

* Patient who had histologically confirmed adenocarcinoma of the prostate.
* Patient must have radiologically documented metastatic disease.
* Patients should have received at least 12 weeks of docetaxel chemotherapy or a cumulative docetaxel dose of 300 mg/m2 and have disease progression on docetaxel-based therapy. Patients must have progressed after prior hormonal therapy (e.g. medical or surgical castration) as defined by a castrate level of testosterone (less than 50 ng/mL). If patient underwent medical castration, it must be continued during the study.
* Progressive disease may be documented by:

  * Non-measurable disease:

    * Serum PSA progression defined as a rise in at least 2 consecutive serum PSA values, each obtained at least 1 week apart and an absolute value greater than 2.0 ng/ml or,
    * Appearance of two or more new lesions on bone scan.
    * Patients with treated epidural lesions and no other epidural progression will be eligible.
  * Measurable disease

    * Documented progression of disease by Response Evaluation Criteria In Solid Tumors (RECIST) criteria demonstrating at least one visceral or soft tissue metastatic lesion (including new lesion).
    * Nodal or visceral progression will be sufficient for trial entry independent of PSA
    * Only lymph nodes ≥ 2 cm in diameter will be used to assess for a change in size.
    * Previously irradiated lesions, primary prostatic lesion, and bone lesions will be considered non-measurable disease.
* Patient is 18 years or older.
* Patient had a Karnofsky Performance Status (KPS) of at least 70% or Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0-2.
* Life expectancy of \> 6 months.
* Patient with adequate organ function as defined as

  * Absolute Neutrophils Count greater than 1500 cells/mm3
  * Platelets greater than 100,000 cells/mm3
  * Hemoglobin greater than 8 g/dL,
  * Adequate liver function as documented by:

    * Total Bilirubin \</= 1.5 times the upper limit of the normal range for the laboratory (ULN). Higher levels are acceptable if these can be attributed to active hemolysis or ineffective erythropoiesis.
    * AST and ALT \</= 2.5 ULN. (In determining eligibility the more abnormal of the two values (AST or ALT) should be used.)
  * Serum creatinine \</= 2.0 mg/dl or \</= 1.5 x institutional upper limit of normal.
* Male patient must be willing to use an acceptable barrier method for contraception; and must agree not to father a child whilst receiving treatment with Azacitidine and up to six months after last dose.
* Patients may have a history of prior malignancy (≥ 5 years prior) provided that the patient is currently disease free and off all therapy for that malignancy. Patients with non-melanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
* Patients must be informed of the investigational nature of the treatment and must give signed written and informed consent.

EXCLUSION CRITERIA:

* Patients who have received strontium 89 (metastron®), Samarium 153 (quadramet®) radiation therapy within 8 weeks of enrollment.
* Evidence of significant active infection during screening for eligibility.
* Patients who have had a psychiatric illness that could potentially interfere with completion of treatment according to protocol.
* Patients who had chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier. There is no wash-out period for patients who received Zytiga.
* Patient who had brain metastases.
* Patient who had history of allergic reactions attributed to compound or similar chemical or biological composition to azacitidine (Vidaza®) or docetaxel or other drugs formulated with polysorbate 80 or mannitol.
* Patient had major surgical procedure within 28 days before Day 1 of treatment.
* Hepatic malignancy.