Vidaza to Restore Hormone Thx Prostate

• Sponsor: US Oncology Research (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00384839
• Collaborator: Celgene Corporation (Industry), University of Southern California (Other)
• Enrollment: 36
• Locations: 13
• Arm: 1
• Duration (Months): 43
• Patients Per Site: 2.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Drug: azacitidine for injectable suspension	Phase 2

Detailed Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 36 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study for the Use of Vidaza™ to Restore Responsiveness of Patients' Prostate Cancers to Hormonal Therapy
• Study Start Date: Apr 1, 2006
• Actual Primary Completion Date: Nov 1, 2009
• Actual Study Completion Date: Nov 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 azacitidine for injectable suspension	Drug: azacitidine for injectable suspension; 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.; Other Names: Vidaza™

Outcome Measures

Primary Outcome Measures

1. Percentage of Patients With PSA Doubling Time >=3 Months. [Until progression or up to a maximum of 12 cycles]

   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.

Secondary Outcome Measures

1. PSA Response Rate [Every 8 weeks for 1 year.]

   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.

2. Objective Response Rate by Recist (ORR) [Every 8 weeks for 1 year.]

   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.

3. Progression-free Survival [Up to 1.5 year.]

   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.

4. 1-year Overall Survival (OS) [Up to 1 year.]

   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.

5. Changes in Fetal Hemoglobin (HbF) With Time. [Up to 1 year.]

   Time from baseline to maximal fetal hemoglobin (HbF).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Rocky Mountain Cancer Center-Midtown	Denver	Colorado	United States	80218
2	Cancer Centers of Florida, P.A.	Ocoee	Florida	United States	34761
3	Minnesota Oncology Hematology, P.A.	Minneapolis	Minnesota	United States	55404
4	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada	United States	89109
5	New York Oncology Hematology, P.C.	Albany	New York	United States	12208
6	Raleigh Hematology Oncology Associates	Cary	North Carolina	United States	27511
7	Northwestern Carolina Oncology Hematology	Hickory	North Carolina	United States	28602
8	Texas Oncology, P.A.	Dallas	Texas	United States	75246
9	Texas Oncology, P.A.	Fort Worth	Texas	United States	76104
10	Tyler Cancer Center	Tyler	Texas	United States	75702
11	Deke Slayton Cancer Center	Webster	Texas	United States	77598
12	Virginia Oncology Associates	Norfolk	Virginia	United States	23502
13	Cancer Care Nrothwest-South	Spokane	Washington	United States	99202

Sponsors and Collaborators

• US Oncology Research
• Celgene Corporation
• University of Southern California

Investigators

• Principal Investigator: Guru Sonpavde, MD, US Oncology Research

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: US Oncology Research
• ClinicalTrials.gov Identifier: NCT00384839
• Other Study ID Numbers: 05015
• First Posted: Oct 6, 2006
• Last Update Posted: Oct 25, 2018
• Last Verified: Sep 1, 2018

• Additional relevant MeSH terms: Prostatic Neoplasms; Azacitidine

Study Results

Participant Flow

Arm/Group Title	Vidaza
Arm/Group Description	azacitidine for injectable suspension : 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.
Period Title: Overall Study
STARTED	36
COMPLETED	28
NOT COMPLETED	8

Baseline Characteristics

Arm/Group Title	Vidaza
Arm/Group Description	azacitidine for injectable suspension : 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.
Overall Participants	36
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	71.1 (9.19)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	36 100%
Race/Ethnicity, Customized (participants) [Number]
Caucasian	33 91.7%
Hispanic	2 5.6%
Black	1 2.8%
Region of Enrollment (participants) [Number]
United States	36 100%

Outcome Measures

1. Primary Outcome

Title	Percentage of Patients With PSA Doubling Time >=3 Months.
Description	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.
Time Frame	Until progression or up to a maximum of 12 cycles

Outcome Measure Data

Analysis Population Description

Evaluable population

Arm/Group Title	Vidaza
Arm/Group Description	azacitidine for injectable suspension : 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.
Measure Participants	34
Number (95% Confidence Interval) [% of patients with PSA-DT>= 3 months]	55.8

2. Secondary Outcome

Title	PSA Response Rate
Description	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.
Time Frame	Every 8 weeks for 1 year.

Outcome Measure Data

Analysis Population Description

Evaluable population

Arm/Group Title	Vidaza
Arm/Group Description	azacitidine for injectable suspension : 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.
Measure Participants	34
Number (95% Confidence Interval) [percentage of participants]	0 0%

3. Secondary Outcome

Title	Objective Response Rate by Recist (ORR)
Description	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.
Time Frame	Every 8 weeks for 1 year.

Outcome Measure Data

Analysis Population Description

Only for patients with lesions evaluable by RECIST criteria at baseline.

Arm/Group Title	Vidaza
Arm/Group Description	azacitidine for injectable suspension : 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.
Measure Participants	13
Number (95% Confidence Interval) [percentage of participants]	0 0%

4. Secondary Outcome

Title	Progression-free Survival
Description	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.
Time Frame	Up to 1.5 year.

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	Vidaza
Arm/Group Description	azacitidine for injectable suspension : 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.
Measure Participants	36
Median (Full Range) [weeks]	12.4

5. Secondary Outcome

Title	1-year Overall Survival (OS)
Description	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.
Time Frame	Up to 1 year.

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	Vidaza
Arm/Group Description	azacitidine for injectable suspension : 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.
Measure Participants	36
Number (95% Confidence Interval) [Probability of Survival at 1-year]	0.73

6. Secondary Outcome

Title	Changes in Fetal Hemoglobin (HbF) With Time.
Description	Time from baseline to maximal fetal hemoglobin (HbF).
Time Frame	Up to 1 year.

Outcome Measure Data

Analysis Population Description

Patients with HbF measurements.

Arm/Group Title	Vidaza
Arm/Group Description	azacitidine for injectable suspension : 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.
Measure Participants	14
Median (Full Range) [weeks]	12.7

Adverse Events

Time Frame	During the whole treatment period, up to 30 days following last dose.
Adverse Event Reporting Description	For treated patients only, assessed at each treatment visit.
Arm/Group Title	Vidaza
Arm/Group Description	azacitidine for injectable suspension : 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.
All Cause Mortality
	Vidaza
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Vidaza
	Affected / at Risk (%)	# Events
Total	1/34 (2.9%)
Gastrointestinal disorders
NAUSEA	1/34 (2.9%)	1
VOMITING	1/34 (2.9%)	1
Other (Not Including Serious) Adverse Events
	Vidaza
	Affected / at Risk (%)	# Events
Total	31/34 (91.2%)
Blood and lymphatic system disorders
ANEMIA	7/34 (20.6%)	9
LEUCOPENIA	3/34 (8.8%)	11
NEUTROPENIA	6/34 (17.6%)	11
THROMBOCYTOPENIA	2/34 (5.9%)	3
Gastrointestinal disorders
ANOREXIA	7/34 (20.6%)	7
CONSTIPATION	13/34 (38.2%)	16
DIARRHEA	3/34 (8.8%)	3
NAUSEA	11/34 (32.4%)	14
VOMITING	10/34 (29.4%)	11
General disorders
FATIGUE	14/34 (41.2%)	16
WEAKNESS	3/34 (8.8%)	3
Metabolism and nutrition disorders
CREATININE SERUM INCREASED	2/34 (5.9%)	2
Nervous system disorders
NEUROPATHY	2/34 (5.9%)	2
Skin and subcutaneous tissue disorders
INJECTION SITE PAIN	2/34 (5.9%)	4
INJECTION SITE REACTION	9/34 (26.5%)	19
PRURITUS	3/34 (8.8%)	3
RASH	3/34 (8.8%)	4

Limitations/Caveats

Further development of azacitidine in patients with prostate cancer may be warranted in randomized trials, alone and in combination with hormonal therapy, chemotherapy and histone deacytelase inhibitors

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.