Bicalutamide and Goserelin or Leuprolide Acetate With or Without Cixutumumab in Treating Patients With Newly Diagnosed Metastatic Prostate Cancer

Prostate Adenocarcinoma Clinical Trial

Official title:

A Randomized Phase II Study of Androgen Deprivation Combined With IMC-A12 Versus Androgen Deprivation Alone for Patients With New Hormone Sensitive Metastatic Prostate Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01120236
• Other study ID #: NCI-2011-02003
• Secondary ID: NCI-2011-02003SW
• Status: Completed
• Phase: Phase 2
• First received: May 7, 2010
• Last updated: February 23, 2018
• Start date: December 2010
• Est. completion date: August 23, 2017

Study information

• Verified date: February 2018
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This randomized phase II trial is studying bicalutamide, goserelin, or leuprolide acetate to see how well they work when given with or without cixutumumab in treating patients with newly diagnosed metastatic prostate cancer. Androgens can cause the growth of prostate cancer cells. Antihormone therapy, such as bicalutamide, goserelin, or leuprolide acetate, may lessen the amount of androgens made by the body. Monoclonal antibodies, such as cixutumumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether bicalutamide, goserelin, or leuprolide acetate are more effective when given with or without cixutumumab in treating prostate cancer.

Description:

PRIMARY OBJECTIVES:

I. To compare the undetectable prostate-specific antigen (PSA) rate (PSA < 0.2 ng/mL) after seven cycles (28 weeks) of protocol treatment between those randomized to a luteinizing hormone-releasing hormone (LHRH) agonist and bicalutamide and those randomized to a LHRH agonist, bicalutamide and IMC-A12 (cixutumumab).

SECONDARY OBJECTIVES:

I. To assess the safety and tolerability of the combination of IMC-A12 with a LHRH agonist and bicalutamide.

II. To compare the proportion of men who do not achieve a PSA of < 4 ng/mL between the two groups.

III. To assess the accuracy of the prognostic model of undetectable PSA that was developed from Southwest Oncology Group (SWOG)-9346 using current trial data from each arm.

IV. To assess serum samples and peripheral blood mononuclear cells (PBMNC) for pharmacodynamic activity with potential biomarkers for IMC-A12 (including, but not limited to: insulin-like growth factor [IGF]-I, free IGF-I, IGF-II, IGF binding protein [IGFBP]2, IGFBP3, growth hormone, insulin and C-peptide) obtained from optional blood specimens both before initiation of androgen deprivation therapy and twelve weeks after initiation of combined therapy.

V. To determine baseline pre-treatment circulating tumor cell (CTC) quantities and response to therapy (for those patients with detectable CTC levels >= 1) twelve weeks later.

VI. In the same subset of patients where CTC levels are obtained, determine baseline serum levels of micro-ribonucleic acids (RNAs) to include but not limited to microRNA (mi)-141 both before initiation of androgen deprivation therapy and twelve weeks after combined therapy.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive androgen deprivation therapy comprising bicalutamide orally (PO) once daily (QD) on days 1-28 and either goserelin acetate subcutaneously (SC) or leuprolide acetate intramuscularly (IM) every 1, 3, 4, 6, or 12 months. Patients also receive cixutumumab intravenously (IV) over 1 hour on days 1 and 15. Treatment repeats every 28 days for 7 courses in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive androgen deprivation therapy comprising bicalutamide and either goserelin acetate or leuprolide acetate as in arm I.

After completion of study treatment, patients are followed up every 6 months for 2 years and then annually for 3 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 211
• Est. completion date: August 23, 2017
• Est. primary completion date: June 2015
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• All patients must have a histologically or cytologically proven diagnosis of adenocarcinoma of the prostate; note: If there is no formal biopsy report documenting the diagnosis of prostate cancer, the patient can be allowed on trial if the PSA level is at least 20, and there are at least three definitive metastatic lesions seen on scan; all patients must have had metastatic (M1) disease as evidenced by soft tissue and/or bony metastases prior to androgen deprivation therapy initiation; patients must have at least one of the following at the time they started androgen deprivation therapy:

• Visceral disease (liver, lung, or other viscera)

• Bone metastases to sites in either the axial (spine, pelvis, ribs, or skull) and/or the appendicular (clavicle, humerus, or femur) skeleton

• Lymph node disease not considered to be encompassed within a single radiotherapy port (e.g., above the aortic bifurcation, etc.)

• Patients who have measurable disease must have radiographic assessment (at least an abdominal/pelvic computed tomography [CT]) within 28 days prior to registration; non-measurable disease must also be assessed (e.g., bone scan) in all patients within 56 days prior to registration; all disease must be assessed and documented on the Baseline Tumor Assessment Form

• Patients must have a PSA >= 5 ng/mL obtained within 90 days prior to initiation of androgen deprivation therapy

• Patients with known brain metastases are not eligible; brain imaging studies are not required for eligibility if the patient has no neurologic signs or symptoms, but if brain imaging studies are performed, they must be negative for disease

• Patient must have had no more than 30 days of prior medical castration for metastatic prostate cancer (prior androgen deprivation therapy is allowed if it was received with curative intent in the neoadjuvant, concurrent, and/or adjuvant fashion and at least 2 years have elapsed since completion of androgen deprivation therapy); the start date of medical castration is considered the day the patient first received an injection of a LHRH agonist, not an oral antiandrogen; if the method of castration is luteinizing hormone releasing hormone (LHRH) agonists (i.e., leuprolide or goserelin), the patient must be willing to continue the use of LHRH agonists and add bicalutamide for combined androgen deprivation therapy (ADT) during protocol treatment; the 30 day window begins from the date of receiving the LHRH agonist, not the oral antiandrogen; if the patient was on a different antiandrogen (e.g. flutamide), the patient must be willing to switch over to bicalutamide; patients must not have received bilateral orchiectomy; patients must not have received or be planning to receive LHRH antagonists (i.e., Degarelix); however, if the patient was initiated on a LHRH antagonist within the 30 day window and is willing to switch to a LHRH agonist with bicalutamide, he may enroll on the late induction group

• Patients who have not already started androgen deprivation therapy must be offered the opportunity to participate in the translational medicine studies; once a patient has started any form of antiandrogen (i.e., either bicalutamide or LHRH agonist), he is not eligible for any translational medicine studies

• Patients must not have received any prior cytotoxic chemotherapy for metastatic prostate cancer; prior cytotoxic chemotherapy with curative intent in the neoadjuvant or adjuvant setting is allowed; patients must not have received any prior treatment with agents that directly inhibit IGF or IGFRs

• Patients must not have received prior strontium-89, rhenium-186, rhenium-188, or samarium-153 radionuclide therapy within 28 days prior to registration

• Patients may have received prior radiation therapy or biologic therapy (e.g. vaccines, immunotherapy, anti-sense, small molecules, monoclonal antibodies); however, at least 28 days must have elapsed since completion of therapy and patient must have recovered from all side effects

• Patients may have received prior surgery; for all major surgeries, at least 28 days must have elapsed since completion and patient must have recovered from all side effects

• Leukocytes >= 3,000 mcL

• Absolute neutrophil count (ANC) >= 1,500 mcL

• Hemoglobin >= 9 g/dL

• Platelets >= 100,000/mcL

• Bilirubin =< 1.5 times the institutional upper limit of normal (ULN) (unless documented Gilbert's disease)

• Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 3 times the institutional ULN, or =< 5 times the institutional ULN if liver metastases are present

• Creatinine =< 2.0 x the institutional ULN or calculated creatinine clearance >= 40 mL/min

• International normalized ratio (INR) =< 1.5

• Partial thromboplastin time (PTT) no more than 5 seconds above the institutional ULN

• Patients receiving prophylactic low dose coumadin or low molecular weight heparin are eligible as long as they meet these coagulation criteria; patients requiring full-dose (therapeutic) anticoagulation are eligible provided that they have been on a stable dose of anticoagulation and the coagulation parameters are stable within the therapeutic range (e.g., INR 2-3 for patients on therapeutic warfarin)

• Patients must have a hemoglobin A1c (HgA1c) =< 7% AND fasting glucose of < 160 mg/dL or below the institutional ULN within 14 days prior to registration; patients with diabetes mellitus who meet this criterion must be on a stable dietary or therapeutic regimen for this condition

• Patients must not have a history of symptomatic congestive heart failure or a known ejection fraction (left ventricular ejection fraction [LVEF]) that is >= 10% below the lower limit of normal (LLN); if left ventricular (LV) dysfunction is suspected, but not confirmed by review of past medical history, a multi gated acquisition scan (MUGA) or echocardiogram must be obtained within 90 days prior to registration

• Patient must not have a history of allergic reaction attributed to compounds of similar chemical or biologic composition to IMC-A12; patients must not have received prior chimerized or murine monoclonal antibody therapy

• Patients must have a Zubrod performance status of 0 - 2; Zubrod performance status 3 will be allowed if from bone pain only

• Patients with human immunodeficiency virus (HIV) positivity requiring antiretroviral therapy are not eligible for this study

• Patients must have no plans to receive concurrent chemotherapy, hormonal therapy (other than the LHRH agonist and oral anti-androgen), radiotherapy, immunotherapy or any other type of therapy for treatment of cancer while on this protocol treatment; concurrent bone targeting agents that do not have effect on PSA (i.e. denosumab or zoledronic acid) are allowed

• Patients must have no plans to receive concurrent five-alpha reductase inhibitors (e.g. finasteride and dutasteride), ketoconazole, diethylstilbestrol/DES, or other estrogen-based therapy while on this protocol treatment

• No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for 5 years

• Men of reproductive potential must have agreed to use an effective contraceptive method while receiving treatment on this study and for at least three months after protocol treatment ends

• All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines

• As part of the OPEN registration process, the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system

Related Conditions & MeSH terms

• Adenocarcinoma
• Prostate Adenocarcinoma
• Prostatic Neoplasms
• Recurrent Prostate Carcinoma
• Stage IV Prostate Cancer

Intervention

Drug:
• Bicalutamide
Given PO

Biological:
• Cixutumumab
Given IV

Drug:
• Goserelin Acetate
Given SC

Other:
• Laboratory Biomarker Analysis
Correlative studies

Drug:
• Leuprolide Acetate
Given IM

Other:
• Pharmacological Study
Correlative studies

Locations

Country	Name	City	State
Canada	BCCA-Vancouver Cancer Centre	Vancouver	British Columbia
United States	Oncare Hawaii Inc-Pali Momi	'Aiea	Hawaii
United States	Pali Momi Medical Center	'Aiea	Hawaii
United States	San Luis Valley Regional Medical Center	Alamosa	Colorado
United States	Saint Anthony's Health	Alton	Illinois
United States	Cancer Care Center at Island Hospital	Anacortes	Washington
United States	AnMed Health Cancer Center	Anderson	South Carolina
United States	Michigan Cancer Research Consortium NCORP	Ann Arbor	Michigan
United States	Saint Joseph Mercy Hospital	Ann Arbor	Michigan
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	University of Colorado Cancer Center - Anschutz Cancer Pavilion	Aurora	Colorado
United States	Bronson Battle Creek	Battle Creek	Michigan
United States	Franciscan Saint Francis Health-Beech Grove	Beech Grove	Indiana
United States	PeaceHealth Saint Joseph Medical Center	Bellingham	Washington
United States	Saint Charles Medical Center-Bend	Bend	Oregon
United States	Spectrum Health Big Rapids Hospital	Big Rapids	Michigan
United States	Billings Clinic Cancer Center	Billings	Montana
United States	Frontier Cancer Center and Blood Institute-Billings	Billings	Montana
United States	Montana Cancer Consortium NCORP	Billings	Montana
United States	Saint Vincent Healthcare	Billings	Montana
United States	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho
United States	Bozeman Deaconess Cancer Center	Bozeman	Montana
United States	Bozeman Deaconess Hospital	Bozeman	Montana
United States	Harrison HealthPartners Hematology and Oncology-Bremerton	Bremerton	Washington
United States	Highline Medical Center-Main Campus	Burien	Washington
United States	Rocky Mountain Oncology	Casper	Wyoming
United States	Providence Regional Cancer System-Centralia	Centralia	Washington
United States	Cancer Center of Kansas - Chanute	Chanute	Kansas
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Danville Regional Medical Center	Danville	Virginia
United States	Dayton NCI Community Oncology Research Program	Dayton	Ohio
United States	Good Samaritan Hospital - Dayton	Dayton	Ohio
United States	Grandview Hospital	Dayton	Ohio
United States	Miami Valley Hospital	Dayton	Ohio
United States	Samaritan North Health Center	Dayton	Ohio
United States	Beaumont Hospital-Dearborn	Dearborn	Michigan
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	Heartland Cancer Research NCORP	Decatur	Illinois
United States	Henry Ford Hospital	Detroit	Michigan
United States	Saint John Hospital and Medical Center	Detroit	Michigan
United States	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan
United States	Cancer Center of Kansas - Dodge City	Dodge City	Kansas
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	The Shaw Regional Cancer Center	Edwards	Colorado
United States	Cancer Center of Kansas - El Dorado	El Dorado	Kansas
United States	Providence Regional Cancer Partnership	Everett	Washington
United States	Fairbanks Memorial Hospital	Fairbanks	Alaska
United States	Saint Francis Hospital	Federal Way	Washington
United States	Blanchard Valley Hospital	Findlay	Ohio
United States	Genesys Hurley Cancer Institute	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	Front Range Cancer Specialists	Fort Collins	Colorado
United States	Poudre Valley Hospital	Fort Collins	Colorado
United States	Brooke Army Medical Center	Fort Sam Houston	Texas
United States	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas
United States	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio
United States	University of Texas Medical Branch	Galveston	Texas
United States	Valley View Hospital Cancer Center	Glenwood Springs	Colorado
United States	Wayne Memorial Hospital	Goldsboro	North Carolina
United States	Saint Mary's Hospital and Regional Medical Center	Grand Junction	Colorado
United States	Cancer Research Consortium of West Michigan NCORP	Grand Rapids	Michigan
United States	Mercy Health Saint Mary's	Grand Rapids	Michigan
United States	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan
United States	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana
United States	Great Falls Clinic	Great Falls	Montana
United States	Wayne Hospital	Greenville	Ohio
United States	Smilow Cancer Hospital Care Center at Saint Francis	Hartford	Connecticut
United States	Saint Peter's Community Hospital	Helena	Montana
United States	Margaret R Pardee Memorial Hospital	Hendersonville	North Carolina
United States	Hines Veterans Administration Hospital	Hines	Illinois
United States	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii
United States	Kuakini Medical Center	Honolulu	Hawaii
United States	Oncare Hawaii Inc-POB II	Honolulu	Hawaii
United States	OnCare Hawaii-Kuakini	Honolulu	Hawaii
United States	Queen's Medical Center	Honolulu	Hawaii
United States	Straub Clinic and Hospital	Honolulu	Hawaii
United States	Tripler Army Medical Center	Honolulu	Hawaii
United States	University of Hawaii Cancer Center	Honolulu	Hawaii
United States	Cancer Center of Kansas-Independence	Independence	Kansas
United States	Swedish Cancer Institute-Issaquah	Issaquah	Washington
United States	Allegiance Health	Jackson	Michigan
United States	Castle Medical Center	Kailua	Hawaii
United States	Glacier Oncology PLLC	Kalispell	Montana
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	Kansas City Veterans Affairs Medical Center	Kansas City	Missouri
United States	University of Kansas Cancer Center	Kansas City	Kansas
United States	Kadlec Clinic Hematology and Oncology	Kennewick	Washington
United States	Kettering Medical Center	Kettering	Ohio
United States	Cancer Center of Kansas-Kingman	Kingman	Kansas
United States	EvergreenHealth Medical Center	Kirkland	Washington
United States	Saint Clare Hospital	Lakewood	Washington
United States	Sparrow Hospital	Lansing	Michigan
United States	Nevada Cancer Research Foundation CCOP	Las Vegas	Nevada
United States	University Medical Center of Southern Nevada	Las Vegas	Nevada
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	Saint Joseph Regional Medical Center	Lewiston	Idaho
United States	Cancer Center of Kansas-Liberal	Liberal	Kansas
United States	Wilcox Memorial Hospital and Kauai Medical Clinic	Lihue	Hawaii
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Saint Mary Mercy Hospital	Livonia	Michigan
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	USC / Norris Comprehensive Cancer Center	Los Angeles	California
United States	Fremont - Rideout Cancer Center	Marysville	California
United States	Loyola University Medical Center	Maywood	Illinois
United States	Montana Cancer Specialists	Missoula	Montana
United States	Saint Patrick Hospital - Community Hospital	Missoula	Montana
United States	University Health-Conway	Monroe	Louisiana
United States	Montrose Memorial Hospital	Montrose	Colorado
United States	Skagit Valley Hospital	Mount Vernon	Washington
United States	Mercy Health Mercy Campus	Muskegon	Michigan
United States	Cancer Center of Kansas - Newton	Newton	Kansas
United States	Providence - Saint Peter Hospital	Olympia	Washington
United States	UF Cancer Center at Orlando Health	Orlando	Florida
United States	Cancer Center of Kansas - Parsons	Parsons	Kansas
United States	Valley Medical Oncology Consultants	Pleasanton	California
United States	Saint Joseph Mercy Oakland	Pontiac	Michigan
United States	Saint Joseph Mercy Port Huron	Port Huron	Michigan
United States	Harrison HealthPartners Hematology and Oncology-Poulsbo	Poulsbo	Washington
United States	Cancer Center of Kansas - Pratt	Pratt	Kansas
United States	MultiCare Good Samaritan Hospital	Puyallup	Washington
United States	Spectrum Health Reed City Hospital	Reed City	Michigan
United States	Reid Health	Richmond	Indiana
United States	University of Rochester	Rochester	New York
United States	Highlands Oncology Group-Rogers	Rogers	Arkansas
United States	University of California Davis Comprehensive Cancer Center	Sacramento	California
United States	Saint Mary's of Michigan	Saginaw	Michigan
United States	Cancer Center of Kansas - Salina	Salina	Kansas
United States	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Group Health Cooperative of Puget Sound Oncology Consortium	Seattle	Washington
United States	Group Health Cooperative-Seattle	Seattle	Washington
United States	Harborview Medical Center	Seattle	Washington
United States	Minor and James Medical PLLC	Seattle	Washington
United States	Pacific Medical Center-First Hill	Seattle	Washington
United States	Swedish Medical Center-First Hill	Seattle	Washington
United States	The Polyclinic	Seattle	Washington
United States	University of Washington Medical Center	Seattle	Washington
United States	Virginia Mason CCOP	Seattle	Washington
United States	United General Hospital	Sedro-Woolley	Washington
United States	Welch Cancer Center	Sheridan	Wyoming
United States	Highland Clinic	Shreveport	Louisiana
United States	Louisiana State University Health Sciences Center Shreveport	Shreveport	Louisiana
United States	Spartanburg Medical Center	Spartanburg	South Carolina
United States	Cancer Care Northwest - Spokane South	Spokane	Washington
United States	Evergreen Hematology and Oncology PS	Spokane	Washington
United States	Rockwood Clinic	Spokane	Washington
United States	Memorial Medical Center	Springfield	Illinois
United States	Iredell Memorial Hospital	Statesville	North Carolina
United States	MultiCare Allenmore Hospital	Tacoma	Washington
United States	Multicare Health System	Tacoma	Washington
United States	Northwest NCI Community Oncology Research Program	Tacoma	Washington
United States	Saint Joseph Medical Center	Tacoma	Washington
United States	Moffitt Cancer Center	Tampa	Florida
United States	Munson Medical Center	Traverse City	Michigan
United States	Upper Valley Medical Center	Troy	Ohio
United States	Tahoe Forest Cancer Center	Truckee	California
United States	Saint John Macomb-Oakland Hospital	Warren	Michigan
United States	Cancer Center of Kansas - Wellington	Wellington	Kansas
United States	Wenatchee Valley Hospital and Clinics	Wenatchee	Washington
United States	Associates In Womens Health	Wichita	Kansas
United States	Cancer Center of Kansas - Wichita	Wichita	Kansas
United States	Cancer Center of Kansas-Wichita Medical Arts Tower	Wichita	Kansas
United States	Via Christi Regional Medical Center	Wichita	Kansas
United States	Wichita NCI Community Oncology Research Program	Wichita	Kansas
United States	Clinton Memorial Hospital	Wilmington	Ohio
United States	Cancer Center of Kansas - Winfield	Winfield	Kansas
United States	Southeast Clinical Oncology Research (SCOR) Consortium NCORP	Winston-Salem	North Carolina
United States	Wright-Patterson Medical Center	Wright-Patterson Air Force Base	Ohio
United States	Metro Health Hospital	Wyoming	Michigan
United States	Greene Memorial Hospital	Xenia	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in Level of IGF-I, Free IGF-I and C-peptide	Serum samples and peripheral blood mononuclear cells (PBMNC) for pharmacodynamic activity with potential biomarkers for IMC-A12 (including, but not limited to: IGF-I, free IGF-I and C-peptide) obtained from optional blood specimens both before initiation of androgen deprivation therapy and twelve weeks after initiation of combined therapy. Results are reported as the difference between baseline and 12 weeks after start of therapy.	Baseline to 12 weeks
Other	Change in Level of IGFBP2, IGFBP3 and Growth Hormone	Serum samples and peripheral blood mononuclear cells (PBMNC) for pharmacodynamic activity with potential biomarkers for IMC-A12 (including, but not limited to: IGFBP2, IGFBP3 and Growth Hormone) obtained from optional blood specimens both before initiation of androgen deprivation therapy and twelve weeks after initiation of combined therapy. Results are reported as the difference between baseline and 12 weeks after start of therapy.	Baseline to 12 weeks
Other	Change in Level of Insulin	Serum samples and peripheral blood mononuclear cells (PBMNC) for pharmacodynamic activity with potential biomarkers for IMC-A12 (insulin) obtained from optional blood specimens both before initiation of androgen deprivation therapy and twelve weeks after initiation of combined therapy. Results are reported as the difference between baseline and 12 weeks after start of therapy.	Baseline to 12 weeks
Primary	Undetectable PSA Rate	Undetectable PSA rate (<= 0.2 ng/mL) after seven cycles (28 weeks) of protocol treatment	7 months
Secondary	Toxicity	Only adverse events that are possibly, probably or definitely related to study drug are reported.	Up to 28 weeks
Secondary	Proportion of Patients Who do Not Achieve a Partial PSA Response	A partial PSA response is considered <= 4 ng/mL	Up to 5 years
Secondary	Accuracy of the Prognostic Model of Undetectable PSA (Developed From SWOG-9346)	The logistic regression algorithm for predicting undetectable PSA that was developed for SWOG-9346 using its baseline risk factors (age at registration, performance status, baseline PSA, and bone pain) will be applied to each arm of this trial to evaluate the level of agreement between the observed and predicted undetectable PSA rates.	Up to 5 years
Secondary	Correlation of microRNA Measures With 28-week PSA Response	The Friedman test will be used to evaluate correlations between microRNA measures (CT) and 28-week PSA response.	Baseline to 28 weeks
Secondary	Correlation of microRNA Measures With Baseline Circulating Tumor Cell (CTC) Counts	The Friedman test will be used to evaluate correlations between microRNA measures (CT) and Baseline CTCs.	Baseline
Secondary	Change in Level of CTCs	Will be correlated with 28-week PSA response.	Baseline to 28 weeks