Vidaza to Restore Hormone Thx Prostate

This is an open label Phase II study. Patients will receive Vidaza for 5 consecutive days (Days 1- 5) of each 28-day cycle. Complete androgen ablation will be continued. Response will be assessed after a minimum of 2 cycles (evaluable patients). PSA response will be evaluated prior to each cycle and % fetal hemoglobin will be evaluated prior to each odd cycle (excluding Cycle 1). Patients will be treated until clinical progression up to a maximum of 12 cycles. A total of 35 patients with advanced metastatic HRPC will be enrolled in this trial.

Inclusion criteria

• A diagnosis of histologically confirmed, progressive, advanced metastatic, or nonmetastatic prostate cancer with documented PSA progression, with a calculated PSA doubling time <3 months, on complete androgen ablation therapy. PSA progression, with or without clinical progression (symptomatic/radiologic as per RECIST) is required; measurable disease is not required.

Baseline PSA values must be followed by 2 serial increases at least 2 weeks apart (no upper limit for time for these 2 samples). Calculated PSA doubling time, for the above PSA values must be <3 months. An automated PSA doubling time calculator may be found at www.mskcc.org/mskcc/html/10088.cfm (see study tools).

• Currently on complete androgen ablation hormone therapy (an LHRH agonist plus an antiandrogen) with testosterone level <50ng/dL). Patients who are on LHRH agonist or other antiandrogenic therapy at entry will continue that therapy while on this study. Anti-androgen withdrawal is not necessary and is precluded before enrollment on the trial. The details of that therapy must be recorded in the CRF. Patients who have had an orchiectomy and who are on antiandrogen therapy are permitted on study.
• An elevated PSA level for patients progressing by PSA criteria is required (see protocol for specific detail).
• Has a Karnofsky Performance Status >70
• Is greater than 18 years of age
• Must meet specific lab values for the following criteria: granulocyte, platelet count, total bilirubin, AST and ALT, serum creatinine, calculated creatinine clearance & urinalysis (see protocol for specific detail).
• If fertile, the patient has agreed to use an acceptable method of birth control to avoid fathering a child for the duration of the study and for a period of 2 months thereafter.
• Has signed a Patient Informed Consent Form
• Has signed a Patient Authorization Form

Exclusion criteria

• Has only clinical progression without evidence of PSA progression
• Has received prior chemotherapy
• Has had prior treatment with Vidaza
• Has a history of hypersensitivity to any component of Vidaza (mannitol)
• Has a history of New York Heart Association (NYHA) heart disease Class III or IV (Appendix III) or myocardial infarction within 6 months prior to Day 1 or unstable arrhythmia or evidence of ischemia on electrocardiogram (ECG)
• Is receiving concurrent immunotherapy
• Is receiving concurrent bisphosphonate therapy; long-standing bisphosphonate therapy (initiated >8 weeks prior to registration) is acceptable. Bisphosphonates started within the prior 8 weeks will not be allowed since this may affect other study endpoints and render their interpretation difficult.
• Has received treatment with radiation therapy, surgery, chemotherapy, ketoconazole, corticosteroids, or an investigational agent within 1 month prior to registration, (6 weeks for radiation therapy, nitrosureas or Mitomycin C)
• Has evidence of central nervous system (CNS) involvement
• Has a serious uncontrolled intercurrent medical or psychiatric illness, including serious infection that requires systemic therapy
• Has a serious uncontrolled nonmalignant disease (liver failure, or other condition) that could compromise protocol objectives in the opinion of the Investigator
• Has a history of other malignancy within the last 5 years (except cured basal cell carcinoma of skin), which could affect the diagnosis or assessment of any of the study drugs
• Is known to be positive for the human immunodeficiency virus (HIV), hepatitis B, or hepatitis C
• Is unable to comply with requirements of study