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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Recurrent Prostate Carcinoma; Stage IIA Prostate Cancer AJCC v7; Stage III Prostate Cancer AJCC v7; Stage I Prostate Cancer AJCC v7; Stage IIB Prostate Cancer AJCC v7
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Drug: Akt Inhibitor MK2206; Other: Clinical Observation; Drug: Bicalutamide

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 108
• Phase: Phase 2

Contacts and Locations

Study Locations

• Ireland
  • Cork, Ireland
    • Cork University Hospital
  • Co Dublin
    • Dublin, Co Dublin, Ireland, 24
      • Tallaght University Hospital
    • Dublin, Co Dublin, Ireland, 4
      • Saint Vincent's University Hospital
    • Dublin, Co Dublin, Ireland, 7
      • Mater Misericordiae University Hospital
    • Dublin, Co Dublin, Ireland, 7
      • Mater Private Hospital
  • Co Galway
    • Galway, Co Galway, Ireland
      • University College Hospital Galway
• United States
  • California
    • Palo Alto, California, United States, 94304
      • VA Palo Alto Health Care System
    • Palo Alto, California, United States, 94304
      • Stanford Cancer Institute Palo Alto
  • Colorado
    • Aurora, Colorado, United States, 80012
      • The Medical Center of Aurora
    • Boulder, Colorado, United States, 80301
      • Boulder Community Hospital
    • Colorado Springs, Colorado, United States, 80907
      • Penrose-Saint Francis Healthcare
    • Denver, Colorado, United States, 80210
      • Porter Adventist Hospital
    • Denver, Colorado, United States, 80218
      • Presbyterian - Saint Lukes Medical Center - Health One
    • Denver, Colorado, United States, 80218
      • SCL Health Saint Joseph Hospital
    • Denver, Colorado, United States, 80220
      • Rose Medical Center
    • Denver, Colorado, United States, 80222
      • Western States Cancer Research NCORP
    • Englewood, Colorado, United States, 80113
      • Swedish Medical Center
    • Fort Collins, Colorado, United States, 80524
      • Poudre Valley Hospital
    • Grand Junction, Colorado, United States, 81501
      • Saint Mary's Hospital and Regional Medical Center
    • Greeley, Colorado, United States, 80631
      • North Colorado Medical Center
    • Lakewood, Colorado, United States, 80228
      • Saint Anthony Hospital
    • Littleton, Colorado, United States, 80122
      • Littleton Adventist Hospital
    • Lone Tree, Colorado, United States, 80124
      • Sky Ridge Medical Center
    • Longmont, Colorado, United States, 80501
      • Longmont United Hospital
    • Loveland, Colorado, United States, 80539
      • McKee Medical Center
    • Parker, Colorado, United States, 80138
      • Parker Adventist Hospital
    • Pueblo, Colorado, United States, 81004
      • Saint Mary Corwin Medical Center
    • Thornton, Colorado, United States, 80229
      • North Suburban Medical Center
    • Wheat Ridge, Colorado, United States, 80033
      • SCL Health Lutheran Medical Center
  • Connecticut
    • Hartford, Connecticut, United States, 06105
      • Smilow Cancer Hospital Care Center at Saint Francis
  • Delaware
    • Lewes, Delaware, United States, 19958
      • Beebe Medical Center
    • Newark, Delaware, United States, 19718
      • Christiana Care Health System-Christiana Hospital
  • District of Columbia
    • Washington, District of Columbia, United States, 20016
      • Sibley Memorial Hospital
  • Florida
    • Jacksonville, Florida, United States, 32224-9980
      • Mayo Clinic in Florida
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital/Winship Cancer Institute
    • Decatur, Georgia, United States, 30033
      • Atlanta VA Medical Center
    • Savannah, Georgia, United States, 31405
      • Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
  • Idaho
    • Boise, Idaho, United States, 83706
      • Saint Alphonsus Cancer Care Center-Boise
  • Illinois
    • Aurora, Illinois, United States, 60504
      • Rush - Copley Medical Center
    • Bloomington, Illinois, United States, 61701
      • Saint Joseph Medical Center
    • Canton, Illinois, United States, 61520
      • Graham Hospital Association
    • Carthage, Illinois, United States, 62321
      • Memorial Hospital
    • Chicago, Illinois, United States, 60612
      • John H Stroger Jr Hospital of Cook County
    • Decatur, Illinois, United States, 62526
      • Decatur Memorial Hospital
    • Decatur, Illinois, United States, 62526
      • Heartland Cancer Research NCORP
    • Eureka, Illinois, United States, 61530
      • Eureka Hospital
    • Evanston, Illinois, United States, 60201
      • NorthShore University HealthSystem-Evanston Hospital
    • Galesburg, Illinois, United States, 61401
      • Illinois CancerCare-Galesburg
    • Havana, Illinois, United States, 62644
      • Mason District Hospital
    • Hinsdale, Illinois, United States, 60521
      • Hinsdale Hematology Oncology Associates Incorporated
    • Macomb, Illinois, United States, 61455
      • Mcdonough District Hospital
    • Moline, Illinois, United States, 61265
      • Trinity Medical Center
    • Normal, Illinois, United States, 61761
      • Carle Cancer Institute Normal
    • Normal, Illinois, United States, 61761
      • Bromenn Regional Medical Center
    • Ottawa, Illinois, United States, 61350
      • Ottawa Regional Hospital and Healthcare Center
    • Pekin, Illinois, United States, 61554
      • OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center
    • Peoria, Illinois, United States, 61636
      • Methodist Medical Center of Illinois
    • Peoria, Illinois, United States, 61637
      • OSF Saint Francis Medical Center
    • Peoria, Illinois, United States, 61615
      • Illinois CancerCare-Peoria
    • Peoria, Illinois, United States, 61614
      • Proctor Hospital
    • Peru, Illinois, United States, 61354
      • Illinois Valley Hospital
    • Princeton, Illinois, United States, 61356
      • Perry Memorial Hospital
    • Rockford, Illinois, United States, 61104
      • Swedish American Hospital
    • Springfield, Illinois, United States, 62781
      • Memorial Medical Center
    • Urbana, Illinois, United States, 61801
      • Carle Cancer Center
  • Indiana
    • Elkhart, Indiana, United States, 46515
      • Elkhart General Hospital
    • Indianapolis, Indiana, United States, 46202
      • Indiana University/Melvin and Bren Simon Cancer Center
    • Indianapolis, Indiana, United States, 46202
      • Sidney and Lois Eskenazi Hospital
    • Indianapolis, Indiana, United States, 46202
      • Richard L. Roudebush Veterans Affairs Medical Center
    • Indianapolis, Indiana, United States, 46219
      • IU Health Central Indiana Cancer Centers-East
    • Indianapolis, Indiana, United States, 46202
      • IU Health Methodist Hospital
    • Kokomo, Indiana, United States, 46904
      • Community Howard Regional Health
    • La Porte, Indiana, United States, 46350
      • IU Health La Porte Hospital
    • Lafayette, Indiana, United States, 47905
      • Horizon Oncology Research LLC
    • Michigan City, Indiana, United States, 46360
      • Franciscan Saint Anthony Health-Michigan City
    • Mishawaka, Indiana, United States, 46545
      • Saint Joseph Regional Medical Center-Mishawaka
    • South Bend, Indiana, United States, 46601
      • Memorial Hospital of South Bend
    • South Bend, Indiana, United States, 46628
      • Northern Indiana Cancer Research Consortium
    • South Bend, Indiana, United States, 46617
      • South Bend Clinic
  • Iowa
    • Ames, Iowa, United States, 50010
      • McFarland Clinic - Ames
    • Clive, Iowa, United States, 50325
      • Medical Oncology and Hematology Associates-West Des Moines
    • Des Moines, Iowa, United States, 50309
      • Iowa Methodist Medical Center
    • Des Moines, Iowa, United States, 50314
      • Mercy Medical Center - Des Moines
    • Des Moines, Iowa, United States, 50309
      • Medical Oncology and Hematology Associates-Des Moines
    • Des Moines, Iowa, United States, 50314
      • Mission Cancer and Blood - Laurel
    • Des Moines, Iowa, United States, 50316
      • Iowa Lutheran Hospital
    • Des Moines, Iowa, United States, 50309
      • Iowa-Wide Oncology Research Coalition NCORP
    • Sioux City, Iowa, United States, 51101
      • Siouxland Regional Cancer Center
    • Sioux City, Iowa, United States, 51102
      • Mercy Medical Center-Sioux City
    • Sioux City, Iowa, United States, 51104
      • Saint Luke's Regional Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University/Sidney Kimmel Cancer Center
    • Easton, Maryland, United States, 21601
      • University of Maryland Shore Medical Center at Easton
    • Elkton, Maryland, United States, 21921
      • Christiana Care - Union Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
    • Springfield, Massachusetts, United States, 01199
      • Baystate Medical Center
  • Michigan
    • Adrian, Michigan, United States, 49221
      • Bixby Medical Center
    • Adrian, Michigan, United States, 49221
      • Hickman Cancer Center
    • Ann Arbor, Michigan, United States, 48106
      • Saint Joseph Mercy Hospital
    • Ann Arbor, Michigan, United States, 48106
      • Michigan Cancer Research Consortium NCORP
    • Dearborn, Michigan, United States, 48124
      • Beaumont Hospital - Dearborn
    • Detroit, Michigan, United States, 48236
      • Ascension Saint John Hospital
    • Flint, Michigan, United States, 48532
      • Genesys Regional Medical Center-West Flint Campus
    • Flint, Michigan, United States, 48503
      • Hurley Medical Center
    • Flint, Michigan, United States, 48503
      • Genesys Hurley Cancer Institute
    • Jackson, Michigan, United States, 49201
      • Allegiance Health
    • Kalamazoo, Michigan, United States, 49007
      • West Michigan Cancer Center
    • Kalamazoo, Michigan, United States, 49007
      • Bronson Methodist Hospital
    • Kalamazoo, Michigan, United States, 49048
      • Borgess Medical Center
    • Lansing, Michigan, United States, 48912
      • University of Michigan Health - Sparrow Lansing
    • Livonia, Michigan, United States, 48154
      • Trinity Health Saint Mary Mercy Livonia Hospital
    • Monroe, Michigan, United States, 48162
      • Mercy Memorial Hospital
    • Monroe, Michigan, United States, 48162
      • Toledo Clinic Cancer Centers-Monroe
    • Pontiac, Michigan, United States, 48341
      • Saint Joseph Mercy Oakland
    • Port Huron, Michigan, United States, 48060
      • Lake Huron Medical Center
    • Saginaw, Michigan, United States, 48601
      • Ascension Saint Mary's Hospital
    • Saint Joseph, Michigan, United States, 49085
      • Lakeland Medical Center Saint Joseph
    • Saint Joseph, Michigan, United States, 49085
      • Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center
    • Warren, Michigan, United States, 48093
      • Saint John Macomb-Oakland Hospital
  • Minnesota
    • Brainerd, Minnesota, United States, 56401
      • Essentia Health Saint Joseph's Medical Center
    • Burnsville, Minnesota, United States, 55337
      • Fairview Ridges Hospital
    • Coon Rapids, Minnesota, United States, 55433
      • Mercy Hospital
    • Duluth, Minnesota, United States, 55805
      • Essentia Health Cancer Center
    • Duluth, Minnesota, United States, 55805
      • Essentia Health Saint Mary's Medical Center
    • Duluth, Minnesota, United States, 55805
      • Miller-Dwan Hospital
    • Edina, Minnesota, United States, 55435
      • Fairview Southdale Hospital
    • Fergus Falls, Minnesota, United States, 56537
      • Lake Region Healthcare Corporation-Cancer Care
    • Fridley, Minnesota, United States, 55432
      • Unity Hospital
    • Hutchinson, Minnesota, United States, 55350
      • Hutchinson Area Health Care
    • Maplewood, Minnesota, United States, 55109
      • Saint John's Hospital - Healtheast
    • Maplewood, Minnesota, United States, 55109
      • Minnesota Oncology Hematology PA-Maplewood
    • Minneapolis, Minnesota, United States, 55415
      • Hennepin County Medical Center
    • Minneapolis, Minnesota, United States, 55407
      • Abbott-Northwestern Hospital
    • New Ulm, Minnesota, United States, 56073
      • New Ulm Medical Center
    • Robbinsdale, Minnesota, United States, 55422
      • North Memorial Medical Health Center
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester
    • Saint Louis Park, Minnesota, United States, 55416
      • Park Nicollet Clinic - Saint Louis Park
    • Saint Louis Park, Minnesota, United States, 55416
      • Metro Minnesota Community Oncology Research Consortium
    • Saint Paul, Minnesota, United States, 55101
      • Regions Hospital
    • Saint Paul, Minnesota, United States, 55102
      • United Hospital
    • Shakopee, Minnesota, United States, 55379
      • Saint Francis Regional Medical Center
    • Stillwater, Minnesota, United States, 55082
      • Lakeview Hospital
    • Waconia, Minnesota, United States, 55387
      • Ridgeview Medical Center
    • Willmar, Minnesota, United States, 56201
      • Rice Memorial Hospital
    • Woodbury, Minnesota, United States, 55125
      • Minnesota Oncology Hematology PA-Woodbury
  • Missouri
    • Cape Girardeau, Missouri, United States, 63703
      • Saint Francis Medical Center
  • Nevada
    • Las Vegas, Nevada, United States, 89169
      • Nevada Cancer Research Foundation NCORP
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Cooper Hospital University Medical Center
    • East Orange, New Jersey, United States, 07018-1095
      • Veterans Adminstration New Jersey Health Care System
    • New Brunswick, New Jersey, United States, 08903
      • Rutgers Cancer Institute of New Jersey
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • University of New Mexico Cancer Center
    • Albuquerque, New Mexico, United States, 87106
      • Hematology Oncology Associates
    • Las Cruces, New Mexico, United States, 88011
      • Memorial Medical Center - Las Cruces
  • New York
    • New York, New York, United States, 10016
      • Laura and Isaac Perlmutter Cancer Center at NYU Langone
    • New York, New York, United States, 10003
      • Mount Sinai Union Square
  • Ohio
    • Bowling Green, Ohio, United States, 43402
      • Toledo Clinic Cancer Centers-Bowling Green
    • Cleveland, Ohio, United States, 44109
      • MetroHealth Medical Center
    • Clyde, Ohio, United States, 43410
      • North Coast Cancer Care-Clyde
    • Elyria, Ohio, United States, 44035
      • Mercy Cancer Center-Elyria
    • Elyria, Ohio, United States, 44035
      • Hematology Oncology Center Incorporated
    • Lima, Ohio, United States, 45804
      • Lima Memorial Hospital
    • Maumee, Ohio, United States, 43537
      • Toledo Clinic Cancer Centers-Maumee
    • Maumee, Ohio, United States, 43537
      • Saint Luke's Hospital
    • Norwalk, Ohio, United States, 44857
      • Fisher-Titus Medical Center
    • Oregon, Ohio, United States, 43616
      • Saint Charles Hospital
    • Oregon, Ohio, United States, 43616
      • Toledo Clinic Cancer Centers-Oregon
    • Sandusky, Ohio, United States, 44870
      • North Coast Cancer Care
    • Steubenville, Ohio, United States, 43952
      • Trinity's Tony Teramana Cancer Center
    • Sylvania, Ohio, United States, 43560
      • ProMedica Flower Hospital
    • Tiffin, Ohio, United States, 44883
      • Mercy Hospital of Tiffin
    • Toledo, Ohio, United States, 43606
      • ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
    • Toledo, Ohio, United States, 43608
      • Saint Vincent Mercy Medical Center
    • Toledo, Ohio, United States, 43623
      • Mercy Health - Saint Anne Hospital
    • Toledo, Ohio, United States, 43623
      • Toledo Clinic Cancer Centers-Toledo
    • Toledo, Ohio, United States, 43614
      • University of Toledo
    • Toledo, Ohio, United States, 43617
      • Toledo Community Hospital Oncology Program CCOP
    • Wauseon, Ohio, United States, 43567
      • Fulton County Health Center
  • Pennsylvania
    • Butler, Pennsylvania, United States, 16001
      • Butler Memorial Hospital
    • Danville, Pennsylvania, United States, 17822
      • Geisinger Medical Center
    • Harrisburg, Pennsylvania, United States, 17109
      • UPMC Pinnacle Cancer Center/Community Osteopathic Campus
    • Hazleton, Pennsylvania, United States, 18201
      • Geisinger Medical Center-Cancer Center Hazleton
    • Langhorne, Pennsylvania, United States, 19047
      • Saint Mary Medical and Regional Cancer Center
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Hospital
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania/Abramson Cancer Center
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Cancer Institute (UPCI)
    • State College, Pennsylvania, United States, 16801
      • Geisinger Medical Group
    • Wilkes-Barre, Pennsylvania, United States, 18711
      • Geisinger Wyoming Valley/Henry Cancer Center
  • Texas
    • Dallas, Texas, United States, 75235
      • Parkland Memorial Hospital
    • Dallas, Texas, United States, 75390
      • UT Southwestern/Simmons Cancer Center-Dallas
  • Virginia
    • Fredericksburg, Virginia, United States, 22401
      • Fredericksburg Oncology Inc
  • Wisconsin
    • Green Bay, Wisconsin, United States, 54301
      • Saint Vincent Hospital Cancer Center Green Bay
    • Manitowoc, Wisconsin, United States, 54221
      • Holy Family Memorial Hospital
    • Marinette, Wisconsin, United States, 54143
      • Bay Area Medical Center
    • New Richmond, Wisconsin, United States, 54017
      • Cancer Center of Western Wisconsin
    • Oconomowoc, Wisconsin, United States, 53066
      • ProHealth Oconomowoc Memorial Hospital
    • Sheboygan, Wisconsin, United States, 53081
      • HSHS Saint Nicholas Hospital
    • Waukesha, Wisconsin, United States, 53188
      • ProHealth Waukesha Memorial Hospital
    • Wisconsin Rapids, Wisconsin, United States, 54494
      • Aspirus Cancer Care - Wisconsin Rapids

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm A (observation and bicalutamide); Patients undergo observation on weeks 1-12. Patients then receive bicalutamide PO 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.	Other: Laboratory Biomarker Analysis; Correlative studies; Other: Clinical Observation; Undergo clinical observation; Other Names: observation; Drug: Bicalutamide; Given PO; Other Names: Casodex; Cosudex; ICI 176,334; ICI 176334
Experimental: Arm B (Akt inhibitor MK2206 and bicalutamide); 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 Akt inhibitor MK2206 and bicalutamide until week 72 in the absence of disease progression or unacceptable toxicity.	Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Akt Inhibitor MK2206; Given PO; Other Names: MK2206; MK 2206; MK-2206; MK-2206 FREE BASE; Drug: Bicalutamide; Given PO; Other Names: Casodex; Cosudex; ICI 176,334; ICI 176334

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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)
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
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
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
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Anna C Ferrari, ECOG-ACRIN Cancer Research Group

Study record dates

Study Major Dates

• Study Start (Actual): December 23, 2010
• Primary Completion (Actual): July 17, 2018
• Study Completion (Estimated): March 7, 2025

Study Registration Dates

• First Submitted: December 1, 2010
• First Submitted That Met QC Criteria: December 1, 2010
• First Posted (Estimated): December 2, 2010

Study Record Updates

• Last Update Posted (Actual): April 8, 2024
• Last Update Submitted That Met QC Criteria: April 5, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Androgen Antagonists; Bicalutamide
• Other Study ID Numbers: NCI-2011-02648 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); U10CA180820 (U.S. NIH Grant/Contract); U10CA021115 (U.S. NIH Grant/Contract); ECOG-E2809; CDR0000689613; 11-00834; E2809 (Other Identifier: CTEP)