Vidaza to Restore Hormone Thx Prostate

Study Overview
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Brief Summary
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The purpose of this research study is to find out what effects (good and bad) Vidaza has on patients with prostate cancer. This investigational drug is not approved by the Food and Drug Administration (FDA) for the treatment of prostate cancer; however, it is approved in myelodysplastic syndrome - a bone marrow disease. The pharmaceutical company involved in this study, Pharmion Corporation, is the manufacturer of Vidaza.

Detailed Description
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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.

Official Title
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Phase II Study for the Use of Vidaza™ to Restore Responsiveness of Patients' Prostate Cancers to Hormonal Therapy

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: azacitidine for injectable suspension


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>azacitidine for injectable suspension | Drug: azacitidine for injectable suspension<br>* Vidaza: 75 mg/m2 for 5 consecutive days (Days 1-5) of each 28 day cycle. A cycle will equal to 28 days. Patient will receive a maximum of 12 cycles.<br>* Other names: Vidaza™;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients With PSA Doubling Time >=3 Months. | To determine if Vidaza can convert hormone-refractory prostate cancer to a hormone-responsive state. This will be assessed by the proportion of patients who have a documented prostate specific antigen (PSA) doubling time >3= months. | Until progression or up to a maximum of 12 cycles | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PSA Response Rate | Complete PSA Response defined as complete normalization of PSA maintained for at least 4 weeks, and partial PSA response defined as a decrease in PSA level of at least 50% from baseline level maintained for at least 4 weeks. | Every 8 weeks for 1 year. | 
| Objective Response Rate by Recist (ORR) | ORR = Complete Response (CR) + Parcial response (PR). CR: Disappearance of all target lesions. PR: At least a 30% decrease in the sum of the LD of target lesions taking as reference the baseline sum LD. | Every 8 weeks for 1 year. | 
| Progression-free Survival | PFS is measured from the date of randomization to the date of first documented disease progression or date of death, whichever comes first. If a patient neither progresses nor dies, this patient will be censored at last contact date. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. | Up to 1.5 year. | 
| 1-year Overall Survival (OS) | OS is measured from the date of randomization to the date of death for a dead patient. If a patient is still alive or is lost to follow up, the patient will be censored at the last contact date. | Up to 1 year. | 
| Changes in Fetal Hemoglobin (HbF) With Time. | Time from baseline to maximal fetal hemoglobin (HbF). | Up to 1 year. |