Bicalutamide With or Without Akt Inhibitor MK2206 in Treating Patients With Previously Treated Prostate Cancer

Recurrent Prostate Carcinoma Clinical Trial

Official title:

Androgen Receptor Modulation Phase II, Randomized Study of MK-2206 - Bicalutamide Combination in Patients With Rising PSA at High-Risk of Progression After Primary Therapy

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01251861
• Other study ID #: NCI-2011-02648
• Secondary ID: NCI-2011-02648EC
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: December 23, 2010
• Est. completion date: March 7, 2025

Study information

• Verified date: January 2024
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase II trial studies how well giving bicalutamide with or without Akt inhibitor MK2206 works in treating patients with previously treated prostate cancer. Androgens can cause the growth of prostate cancer cells. Antihormone therapy, such as bicalutamide, may lessen the amount of androgens made by the body. Akt inhibitor MK2206 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether bicalutamide is more effective with or without Akt inhibitor MK2206 in treating prostate cancer.

Description:

PRIMARY OBJECTIVES:

I. To compare the two regimens on the proportion of patients with undetectable prostate-specific antigen (PSA) level (< 0.2 ng/mL) at 44 weeks.

SECONDARY OBJECTIVES:

I. To assess the proportion of patients with PSA decline >= 85% at 44 weeks on the combination therapy arm compared to that of bicalutamide monotherapy arm.

II. To assess the distribution of best PSA response in each study arm. III. To assess the time to PSA progression in each arm of the study. IV. To assess the time to PSA nadir in each arm of the study. V. To assess the duration of PSA response in each arm of the study. VI. To characterize the PSA slope pre-study, during treatment, and off treatment.

VII. To evaluate the safety and tolerability of MK-2206 (Akt inhibitor MK2206) in this patient population.

VIII. To determine whether Gleason score has any effect on PSA response to treatment.

IX. To determine whether prior hormonal therapy has any effect on PSA response to treatment.

TERTIARY OBJECTIVES:

I. Samples of the primary tumor specimen will be retrieved for banking and future analysis of the molecular profile of the primary prostate cancer (PC) tissues with emphasis on the androgen receptor (AR) and protein kinase B (Akt) upstream and downstream signaling pathways.

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

ARM A: Patients undergo observation on weeks 1-12. Patients then receive bicalutamide* orally (PO) once daily (QD) on weeks 13-44. Patients with a PSA decline of >= 50% may continue on bicalutamide until week 72 in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive Akt inhibitor MK2206** PO once per week on weeks 1-44 and bicalutamide* PO QD on weeks 13-44. Patients with a PSA decline of >= 50% may continue on MK2206 and bicalutamide until week 72 in the absence of disease progression or unacceptable toxicity.

NOTE: *Patients may begin bicalutamide on weeks 4-11 if the disease worsens.

NOTE: **Patients on Akt inhibitor MK2206 with a PSA < 0.2 ng/mL by week 12 do not receive bicalutamide until PSA rises to >= 0.2 ng/mL.

After completion of study therapy, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then every year for up to 10 years.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 108
• Est. completion date: March 7, 2025
• Est. primary completion date: July 17, 2018
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patient must have histologically confirmed diagnosis of prostate cancer

• Patient must have had previous treatment with definitive surgery or radiation therapy or cryoablation

• Patient may have prior salvage therapy (surgery, radiation or other local ablative procedures) within 4 weeks prior to randomization if the intent was for cure; prophylactic radiotherapy to prevent gynecomastia within 4 weeks prior to randomization is allowed

• Patient must have no evidence of metastatic disease on physical exam, computed tomography (CT) abdomen/pelvis (or magnetic resonance imaging [MRI]), chest x-ray (or CT chest) and bone scan within 8 weeks prior to randomization

• Patient may have had prior neoadjuvant and/or adjuvant therapy (chemotherapy, vaccines or experimental agents) within 4 weeks prior to randomization, if the PSA rise and PSA doubling time (PSADT) were documented after the testosterone level was > 150 ng/dL

• Patient may not have had therapy modulating testosterone levels (such as luteinizing-hormone, releasing-hormone agonists/antagonists and antiandrogens) within 1 year prior to randomization, unless it was in the neoadjuvant and/or adjuvant setting; agents such as 5 alpha reductase inhibitors, ketoconazole, abiraterone, systemic steroids, or herbal supplements known to decrease PSA levels including any dose of megestrol acetate, finasteride (e.g., Saw Palmetto and PC-SPES, African pygeum extract, lycopene, alanine, glutamic acid and glycine, beta-sitosterol, lycopene, nettle root extract, quercitin, Belizian Man Vine extract, mulra puama extract and epimedium extract campesterol, beta-sitosterol, stigmasterol, sitostanol and brassicasterol) are not permitted at any time during the period that the PSA values are being collected

• Patient must have hormone-sensitive prostate cancer as evident by a serum total testosterone level > 150 ng/dL within 12 weeks prior to randomization

• Patient must have evidence of biochemical failure after primary therapy and subsequent progression

• Biochemical failure is declared when the PSA reaches a threshold value after primary treatment and it differs for radical prostatectomy or radiation therapy

• For radical prostatectomy the threshold for this study is PSA >= 0.4 ng/mL

• For radiation therapy the threshold is a PSA rise of 2 ng/mL above the nadir PSA achieved post radiation with or without hormone therapy (2006 Radiation Therapy Oncology Group [RTOG]-American Society for Radiation Oncology [ASTRO] Consensus definition)

• PSA progression requires a PSA rise above the threshold (PSA1) measured at any time point since the threshold was reached

• The PSADT must be < 12 months; requires two consecutive PSA rises (PSA2 and PSA3) above the PSA1; PSA2 and PSA3 must be obtained within 6 months of study entry; all baseline PSAs should be obtained, preferably, at the same reference lab

• PSADT calculation needs 3 PSA values:

• PSA1 is any PSA value that is equal or greater than the threshold PSA (0.4 ng/mL for radical prostatectomy or 2 ng/mL above the nadir for primary radiation therapy) indicating biochemical relapse

• PSA2 must be higher than PSA1, obtained at least 2 weeks after PSA1 and within 6 months or less from randomization

• PSA3 must be higher than PSA2 and obtained at least 2 weeks after PSA2

• Baseline PSA must have reached a minimum of 2 ng/mL but be no greater than 50 ng/mL and equal or higher than PSA3; PSA3 may be used as baseline PSA if obtained within 1 week of randomization

• Patient's PSA doubling time (PSADT) must be less than 12 months

• Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

• Granulocytes >= 1,500/mm^3

• Platelet count >= 100,000/mm^3

• Serum creatinine within normal institutional limits or creatinine clearance >= 50 ml/min for patients with creatinine levels above institutional normal

• Serum total bilirubin =< 1.5 times upper limit of normal (ULN)

• Alkaline phosphatase (ALP) =< 2.5 x ULN

• Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 2.5 x institutional upper limit of normal

• Human immunodeficiency virus (HIV)-positive patients are excluded from this study

• Patient cannot receive concurrent therapeutic administration of anticoagulant therapy; low dosage aspirin =< 325 mg per day is allowed

• Patients with impaired cardiac function including any one of the following will be excluded from entry on study:

• Baseline corrected QT interval (QTc) > 450 msec (male) (patients with QTc 450-480 msec will be allowed to participate in this trial if they do not have any of the other cardiac conditions mentioned in this section)

• Patients with congenital long QT syndrome

• History of sustained ventricular tachycardia

• Any history of ventricular fibrillation or torsades de pointes

• Concomitant use of drugs with a risk of causing torsades de pointes

• Bradycardia defined as heart rate < 50 beats per minute; patients with a pacemaker and heart rate >= 50 beats per minute are eligible

• Myocardial infarction or unstable angina within 6 months of study entry

• Congestive heart failure (New York Heart Association class III or IV)

• Right bundle branch block and left anterior hemi-block (bifascicular block)

• Patient must not have gastrointestinal (GI) tract disease resulting in an inability to take oral medication, malabsorption syndrome, a requirement for intravenous (IV) alimentation, prior surgical procedures affecting absorption, uncontrolled inflammatory GI disease (e.g., Crohn's, ulcerative colitis)

• Patient may not be receiving any other investigational agents or receiving concurrent anticancer therapy (chemotherapy, immunotherapy, radiation therapy, surgery for cancer, or experimental medications) at time of randomization

• Patient may not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to MK-2206 or bicalutamide

• Patient must not have any uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

• Patients with diabetes or at risk for hyperglycemia MUST not be excluded from trials with MK-2206, but the hyperglycemia should be well controlled before the patient enters the trial

• Patients receiving any medications or substances that are inhibitors or inducers of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) are ineligible

• Patient must NOT have previous or concurrent malignancy; exceptions are made for patients who meet any of the following conditions:

• Basal cell or squamous cell carcinoma of the skin OR

• Prior malignancy has been adequately treated and patient has been continuously disease free for >= 2 years

• Patient must agree to use barrier contraception during and for 3 months after discontinuation of study treatment; if patient impregnates a woman while on treatment or within 3 months of discontinuing treatment, he should inform his treating physician immediately

• Patients must discontinue use of enzyme-inducing anti-epileptic drugs (EIAEDs) >= 14 days prior to study enrollment; the investigator may prescribe non-EIAEDs; patients who must begin EIAED therapy while on study will be allowed to remain

• Patients must not be taking cytochrome P450 enzyme-inducing antiepileptic drugs (phenytoin, carbamazepine or phenobarbital), St John's Wort, ketoconazole, dexamethasone, the dysrhythmic drugs (terfenadine, quinidine, procainamide, sotalol, probucol, bepridil, indapamide or flecainide), haloperidol, risperidone, rifampin, grapefruit, or grapefruit juice within two weeks of randomization and during the course of therapy

• Patients may have received targeted agents (angiogenesis inhibitors, epidermal growth factor receptor [EGFR] inhibitors, mammalian target of rapamycin [mTOR] inhibitors, phosphatidylinositol 3 kinase [PI3K] inhibitors, etc.), however patients must have discontinued treatment with the targeted agent(s) at least 4 weeks prior to enrollment; if the patient stopped targeted agent(s) due to unresolved or persistent grade 3 or 4 toxicity, patient cannot be enrolled onto the study regardless of the length of time since discontinuation of treatment with targeted agent(s)

Related Conditions & MeSH terms

• Prostatic Neoplasms
• Recurrent Prostate Carcinoma
• Stage I Prostate Cancer AJCC v7
• Stage IIA Prostate Cancer AJCC v7
• Stage IIB Prostate Cancer AJCC v7
• Stage III Prostate Cancer AJCC v7

Intervention

Drug:
• Akt Inhibitor MK2206
Given PO
• Bicalutamide
Given PO

Other:
• Clinical Observation
Undergo clinical observation
• Laboratory Biomarker Analysis
Correlative studies

Locations

Country	Name	City	State
Ireland	Cork University Hospital	Cork
Ireland	Mater Misericordiae University Hospital	Dublin	Co Dublin
Ireland	Mater Private Hospital	Dublin	Co Dublin
Ireland	Saint Vincent's University Hospital	Dublin	Co Dublin
Ireland	Tallaght University Hospital	Dublin	Co Dublin
Ireland	University College Hospital Galway	Galway	Co Galway
United States	Bixby Medical Center	Adrian	Michigan
United States	Hickman Cancer Center	Adrian	Michigan
United States	Hematology Oncology Associates	Albuquerque	New Mexico
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	McFarland Clinic - Ames	Ames	Iowa
United States	Michigan Cancer Research Consortium NCORP	Ann Arbor	Michigan
United States	Trinity Health Saint Joseph Mercy Hospital Ann Arbor	Ann Arbor	Michigan
United States	Emory University Hospital/Winship Cancer Institute	Atlanta	Georgia
United States	Rush - Copley Medical Center	Aurora	Illinois
United States	The Medical Center of Aurora	Aurora	Colorado
United States	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland
United States	OSF Saint Joseph Medical Center	Bloomington	Illinois
United States	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho
United States	Tufts Medical Center	Boston	Massachusetts
United States	Boulder Community Hospital	Boulder	Colorado
United States	Toledo Clinic Cancer Centers-Bowling Green	Bowling Green	Ohio
United States	Essentia Health Saint Joseph's Medical Center	Brainerd	Minnesota
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Butler Memorial Hospital	Butler	Pennsylvania
United States	Cooper Hospital University Medical Center	Camden	New Jersey
United States	Graham Hospital Association	Canton	Illinois
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
United States	Memorial Hospital	Carthage	Illinois
United States	John H Stroger Jr Hospital of Cook County	Chicago	Illinois
United States	MetroHealth Medical Center	Cleveland	Ohio
United States	Mission Cancer and Blood - West Des Moines	Clive	Iowa
United States	North Coast Cancer Care-Clyde	Clyde	Ohio
United States	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado
United States	Mercy Hospital	Coon Rapids	Minnesota
United States	Parkland Memorial Hospital	Dallas	Texas
United States	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Beaumont Hospital - Dearborn	Dearborn	Michigan
United States	Atlanta VA Medical Center	Decatur	Georgia
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	Heartland Cancer Research NCORP	Decatur	Illinois
United States	Porter Adventist Hospital	Denver	Colorado
United States	Presbyterian - Saint Lukes Medical Center - Health One	Denver	Colorado
United States	Rose Medical Center	Denver	Colorado
United States	SCL Health Saint Joseph Hospital	Denver	Colorado
United States	Western States Cancer Research NCORP	Denver	Colorado
United States	Iowa Lutheran Hospital	Des Moines	Iowa
United States	Iowa Methodist Medical Center	Des Moines	Iowa
United States	Iowa-Wide Oncology Research Coalition NCORP	Des Moines	Iowa
United States	Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Mission Cancer and Blood - Des Moines	Des Moines	Iowa
United States	Mission Cancer and Blood - Laurel	Des Moines	Iowa
United States	Ascension Saint John Hospital	Detroit	Michigan
United States	Essentia Health Cancer Center	Duluth	Minnesota
United States	Essentia Health Saint Mary's Medical Center	Duluth	Minnesota
United States	Miller-Dwan Hospital	Duluth	Minnesota
United States	Veterans Adminstration New Jersey Health Care System	East Orange	New Jersey
United States	University of Maryland Shore Medical Center at Easton	Easton	Maryland
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Elkhart General Hospital	Elkhart	Indiana
United States	Christiana Care - Union Hospital	Elkton	Maryland
United States	Hematology Oncology Center Incorporated	Elyria	Ohio
United States	Mercy Cancer Center-Elyria	Elyria	Ohio
United States	Swedish Medical Center	Englewood	Colorado
United States	Eureka Hospital	Eureka	Illinois
United States	NorthShore University HealthSystem-Evanston Hospital	Evanston	Illinois
United States	Lake Region Healthcare Corporation-Cancer Care	Fergus Falls	Minnesota
United States	Genesys Hurley Cancer Institute	Flint	Michigan
United States	Genesys Regional Medical Center-West Flint Campus	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	Poudre Valley Hospital	Fort Collins	Colorado
United States	Fredericksburg Oncology Inc	Fredericksburg	Virginia
United States	Unity Hospital	Fridley	Minnesota
United States	Illinois CancerCare-Galesburg	Galesburg	Illinois
United States	Saint Mary's Hospital and Regional Medical Center	Grand Junction	Colorado
United States	Banner North Colorado Medical Center	Greeley	Colorado
United States	Saint Vincent Hospital Cancer Center Green Bay	Green Bay	Wisconsin
United States	UPMC Pinnacle Cancer Center/Community Osteopathic Campus	Harrisburg	Pennsylvania
United States	Smilow Cancer Hospital Care Center at Saint Francis	Hartford	Connecticut
United States	Mason District Hospital	Havana	Illinois
United States	Geisinger Medical Center-Cancer Center Hazleton	Hazleton	Pennsylvania
United States	Hinsdale Hematology Oncology Associates Incorporated	Hinsdale	Illinois
United States	Hutchinson Area Health Care	Hutchinson	Minnesota
United States	Indiana University/Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	IU Health Central Indiana Cancer Centers-East	Indianapolis	Indiana
United States	IU Health Methodist Hospital	Indianapolis	Indiana
United States	Richard L. Roudebush Veterans Affairs Medical Center	Indianapolis	Indiana
United States	Sidney and Lois Eskenazi Hospital	Indianapolis	Indiana
United States	Allegiance Health	Jackson	Michigan
United States	Mayo Clinic in Florida	Jacksonville	Florida
United States	Borgess Medical Center	Kalamazoo	Michigan
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Community Howard Regional Health	Kokomo	Indiana
United States	IU Health La Porte Hospital	La Porte	Indiana
United States	Horizon Oncology Research LLC	Lafayette	Indiana
United States	Saint Anthony Hospital	Lakewood	Colorado
United States	Saint Mary Medical and Regional Cancer Center	Langhorne	Pennsylvania
United States	University of Michigan Health - Sparrow Lansing	Lansing	Michigan
United States	Memorial Medical Center - Las Cruces	Las Cruces	New Mexico
United States	Nevada Cancer Research Foundation NCORP	Las Vegas	Nevada
United States	Beebe Medical Center	Lewes	Delaware
United States	Lima Memorial Hospital	Lima	Ohio
United States	Littleton Adventist Hospital	Littleton	Colorado
United States	Trinity Health Saint Mary Mercy Livonia Hospital	Livonia	Michigan
United States	Sky Ridge Medical Center	Lone Tree	Colorado
United States	Longmont United Hospital	Longmont	Colorado
United States	Banner McKee Medical Center	Loveland	Colorado
United States	Mcdonough District Hospital	Macomb	Illinois
United States	Holy Family Memorial Hospital	Manitowoc	Wisconsin
United States	Minnesota Oncology Hematology PA-Maplewood	Maplewood	Minnesota
United States	Saint John's Hospital - Healtheast	Maplewood	Minnesota
United States	Bay Area Medical Center	Marinette	Wisconsin
United States	Saint Luke's Hospital	Maumee	Ohio
United States	Toledo Clinic Cancer Centers-Maumee	Maumee	Ohio
United States	Franciscan Saint Anthony Health-Michigan City	Michigan City	Indiana
United States	Abbott-Northwestern Hospital	Minneapolis	Minnesota
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	Saint Joseph Regional Medical Center-Mishawaka	Mishawaka	Indiana
United States	Trinity Medical Center	Moline	Illinois
United States	Mercy Memorial Hospital	Monroe	Michigan
United States	Toledo Clinic Cancer Centers-Monroe	Monroe	Michigan
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Cancer Center of Western Wisconsin	New Richmond	Wisconsin
United States	New Ulm Medical Center	New Ulm	Minnesota
United States	Laura and Isaac Perlmutter Cancer Center at NYU Langone	New York	New York
United States	Mount Sinai Union Square	New York	New York
United States	Christiana Care Health System-Christiana Hospital	Newark	Delaware
United States	Bromenn Regional Medical Center	Normal	Illinois
United States	Carle Cancer Institute Normal	Normal	Illinois
United States	Fisher-Titus Medical Center	Norwalk	Ohio
United States	ProHealth Oconomowoc Memorial Hospital	Oconomowoc	Wisconsin
United States	Saint Charles Hospital	Oregon	Ohio
United States	Toledo Clinic Cancer Centers-Oregon	Oregon	Ohio
United States	Ottawa Regional Hospital and Healthcare Center	Ottawa	Illinois
United States	Stanford Cancer Institute Palo Alto	Palo Alto	California
United States	VA Palo Alto Health Care System	Palo Alto	California
United States	Parker Adventist Hospital	Parker	Colorado
United States	OSF Saint Francis Radiation Oncology at Pekin	Pekin	Illinois
United States	Illinois CancerCare-Peoria	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	OSF Saint Francis Medical Center	Peoria	Illinois
United States	Proctor Hospital	Peoria	Illinois
United States	Illinois Valley Hospital	Peru	Illinois
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	University of Pennsylvania/Abramson Cancer Center	Philadelphia	Pennsylvania
United States	University of Pittsburgh Cancer Institute (UPCI)	Pittsburgh	Pennsylvania
United States	Trinity Health Saint Joseph Mercy Oakland Hospital	Pontiac	Michigan
United States	Lake Huron Medical Center	Port Huron	Michigan
United States	Perry Memorial Hospital	Princeton	Illinois
United States	Saint Mary Corwin Medical Center	Pueblo	Colorado
United States	North Memorial Medical Health Center	Robbinsdale	Minnesota
United States	Mayo Clinic in Rochester	Rochester	Minnesota
United States	Swedish American Hospital	Rockford	Illinois
United States	Ascension Saint Mary's Hospital	Saginaw	Michigan
United States	Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center	Saint Joseph	Michigan
United States	Corewell Health Lakeland Hospitals - Saint Joseph Hospital	Saint Joseph	Michigan
United States	Metro Minnesota Community Oncology Research Consortium	Saint Louis Park	Minnesota
United States	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota
United States	Regions Hospital	Saint Paul	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	North Coast Cancer Care	Sandusky	Ohio
United States	Lewis Cancer and Research Pavilion at Saint Joseph's/Candler	Savannah	Georgia
United States	Saint Francis Regional Medical Center	Shakopee	Minnesota
United States	HSHS Saint Nicholas Hospital	Sheboygan	Wisconsin
United States	Mercy Medical Center-Sioux City	Sioux City	Iowa
United States	Saint Luke's Regional Medical Center	Sioux City	Iowa
United States	Siouxland Regional Cancer Center	Sioux City	Iowa
United States	Memorial Hospital of South Bend	South Bend	Indiana
United States	Northern Indiana Cancer Research Consortium	South Bend	Indiana
United States	South Bend Clinic	South Bend	Indiana
United States	Baystate Medical Center	Springfield	Massachusetts
United States	Memorial Medical Center	Springfield	Illinois
United States	Geisinger Medical Group	State College	Pennsylvania
United States	Trinity's Tony Teramana Cancer Center	Steubenville	Ohio
United States	Lakeview Hospital	Stillwater	Minnesota
United States	ProMedica Flower Hospital	Sylvania	Ohio
United States	North Suburban Medical Center	Thornton	Colorado
United States	Mercy Hospital of Tiffin	Tiffin	Ohio
United States	Mercy Health - Saint Anne Hospital	Toledo	Ohio
United States	Mercy Health - Saint Vincent Hospital	Toledo	Ohio
United States	ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital	Toledo	Ohio
United States	Toledo Clinic Cancer Centers-Toledo	Toledo	Ohio
United States	Toledo Community Hospital Oncology Program CCOP	Toledo	Ohio
United States	University of Toledo	Toledo	Ohio
United States	Carle Cancer Center	Urbana	Illinois
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	Saint John Macomb-Oakland Hospital	Warren	Michigan
United States	Sibley Memorial Hospital	Washington	District of Columbia
United States	ProHealth Waukesha Memorial Hospital	Waukesha	Wisconsin
United States	Fulton County Health Center	Wauseon	Ohio
United States	SCL Health Lutheran Medical Center	Wheat Ridge	Colorado
United States	Geisinger Wyoming Valley/Henry Cancer Center	Wilkes-Barre	Pennsylvania
United States	Rice Memorial Hospital	Willmar	Minnesota
United States	Aspirus Cancer Care - Wisconsin Rapids	Wisconsin Rapids	Wisconsin
United States	Minnesota Oncology Hematology PA-Woodbury	Woodbury	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Ireland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Samples of the Primary Tumor Specimen Will be Retrieved for Banking and Future Analysis of the Molecular Profile of the Primary PC Tissues With Emphasis on the AR and Akt Upstream and Downstream Signaling Pathways.	Biospecimen banking for future analysis; no data to be reported	Baseline
Primary	The Proportion of Patients With Undetectable PSA Level (< 0.2 ng/mL) at 44 Weeks	The proportion of patients with undetectable PSA level (< 0.2 ng/mL) at 44 weeks, defined as number of patients with undetectable PSA level at 44 weeks divided by number of patients randomized.	44 weeks
Secondary	Proportion of Patients With PSA Decline > 85% at 44 Weeks	Proportion of patients with PSA decline > 85% at 44 weeks from baseline, defined as number of patients with PSA decline > 85% at 44 weeks from baseline divided by number of patients randomized.	44 weeks
Secondary	Proportion of Patients With PSA Response	PSA complete response (CR) is defined as a PSA <0.2 ng/mL confirmed on two consecutive additional determinations taken at least 4 weeks apart. PSA partial response (PR) is defined as a reduction in PSA = 50% from baseline without evidence of progression (confirmed on two consecutive additional determinations taken at least 4 weeks apart). Either CR or PR is considered as a PSA response.	Assessed every 3 months for 2 years, every 6 months for 3 years, and then annually up to 10 years
Secondary	Time to PSA Progression	Time to PSA progression was defined as the time from randomization to PSA progression or date of last disease assessment showing progression-free. Development of clinical progression is also considered as an event.; For patients (pts) who achieved a = 50% decline in PSA (confirmed on two consecutive determinations taken at least 4 weeks apart), progression is defined as an increase in PSA by 50% above baseline or nadir, whichever is lowest, confirmed by a 2nd PSA rise at least two weeks later. The PSA rise must be >= 5 ng/mL.; For pts with an undetectable PSA nadir (< 0.2 ng/mL confirmed on two consecutive determinations taken at least 4 weeks apart), progression is defined as PSA = 0.2 ng/mL confirmed by a 2nd PSA rise at least 2 weeks later.; For pts whose PSA has not decreased by 50%, progression is defined as an increase in PSA of = 50% of baseline or nadir PSA, whichever is lowest, confirmed by a repeat PSA at least 2 weeks later. The PSA must have risen by >= 5 ng/mL	Assessed every 3 months for 2 years, every 6 months for 3 years, and then annually up to 10 years
Secondary	Time to PSA Nadir	Time to PSA nadir was defined as the time from randomization to the date that PSA nadir, the lowest PSA value achieved after randomization, was documented. This analysis was performed among patients whose PSA level decreased after randomization compared to baseline.	Assessed every 3 months for 2 years, every 6 months for 3 years, and then annually up to 10 years
Secondary	Duration of PSA Response	Duration of PSA response was defined as the time from the date PSA criteria were met for complete response (CR) or partial response (PR), whichever status was recorded first, to the date of PSA progression. Patients without documented PSA progression were censored at the date of last disease assessment. Duration of PSA response is analyzed among responders (PSA CR or PR).	Assessed every 3 months for 2 years, every 6 months for 3 years, and then annually up to 10 years
Secondary	PSA Slope Prior to Randomization	PSA slopes were assessed by multiple PSA values prior to randomization. Linear regression was used to calculate PSA slope using natural log-transformed PSA values on the time of PSA measurements for each patient.	Baseline (pre-randomization)
Secondary	PSA Slope After Randomization and Before Starting Bicalutamide	PSA slopes were assessed by multiple PSA values from randomization to starting bicalutamide treatment. Linear regression was used to calculate PSA slope using natural log-transformed PSA values on the time of PSA measurements for each patient.	After randomization and prior to starting bicalutamide
Secondary	PSA Slope After Starting Bicalutamide Treatment	PSA slopes were assessed by multiple PSA values after starting bicalutamide treatment. Linear regression was used to calculate PSA slope using natural log-transformed PSA values on the time of PSA measurements for each patient.	Assessed every 3 months for 2 years, every 6 months for 3 years, and then annually up to 10 years
Secondary	The Association Between Gleason Score and PSA Response	The association between PSA response (responder vs non-responder) and Gleason score (<7, 7 vs. >7) was evaluated by logistic regression with adjustment for treatment assignment.; Based on the biopsy sample, a Gleason grade is assigned to the most predominant pattern in the biopsy and a second Gleason grade is assigned to the second most predominant pattern. The two grades will then be added together to determine the Gleason score. Gleason scores range from 2-10. The higher the Gleason score, the more aggressive the cancer is likely to be.	Assessed every 3 months for 2 years, every 6 months for 3 years, and then annually up to 10 years
Secondary	The Association Between Prior Hormonal Therapy and PSA Response	The association between PSA response (responder vs non-responder) and prior hormonal therapy (yes vs. no) was evaluated by logistic regression with adjustment for treatment assignment.	Assessed every 3 months for 2 years, every 6 months for 3 years, and then annually up to 10 years