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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


Phase 2
18 Years
N/A
Open (Enrolling)
Male
Recurrent Prostate Cancer, Stage I Prostate Cancer, Stage IIA Prostate Cancer, Stage IIB Prostate Cancer, Stage III Prostate Cancer

Thank you

Trial Information

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


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 I: 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 II: 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.


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 RTGO-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 normal 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 =< 2.5 times ULN

- Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and
serum glutamic pyruvic 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 Fridericia 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 (CYP 450) 3A4 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

- The effect of the study medications on the developing human fetus are unknown; for
this reason, 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)

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Proportion of patients with undetectable PSA level (< 0.2 ng/mL)

Outcome Time Frame:

44 weeks

Safety Issue:

No

Principal Investigator

Anna Ferrari

Investigator Role:

Principal Investigator

Investigator Affiliation:

Eastern Cooperative Oncology Group

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2011-02648

NCT ID:

NCT01251861

Start Date:

December 2010

Completion Date:

Related Keywords:

  • Recurrent Prostate Cancer
  • Stage I Prostate Cancer
  • Stage IIA Prostate Cancer
  • Stage IIB Prostate Cancer
  • Stage III Prostate Cancer
  • Prostatic Neoplasms

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Johns Hopkins UniversityBaltimore, Maryland  21205
Mayo ClinicRochester, Minnesota  55905
Fox Chase Cancer CenterPhiladelphia, Pennsylvania  19111
Hurley Medical CenterFlint, Michigan  48503
Boulder Community HospitalBoulder, Colorado  80301-9019
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Bronson Methodist HospitalKalamazoo, Michigan  49007
West Michigan Cancer CenterKalamazoo, Michigan  49007-3731
Borgess Medical CenterKalamazooaa, Michigan  49001
Fairview Ridges HospitalBurnsville, Minnesota  55337
Hutchinson Area Health CareHutchinson, Minnesota  55350
United HospitalSt. Paul, Minnesota  55102
Ridgeview Medical CenterWaconia, Minnesota  55387
Geisinger Medical CenterDanville, Pennsylvania  17822-0001
Abramson Cancer Center of the University of PennsylvaniaPhiladelphia, Pennsylvania  19104-4283
Methodist Medical Center of IllinoisPeoria, Illinois  61636
Memorial Hospital of South BendSouth Bend, Indiana  46601
Beth Israel Medical CenterNew York, New York  10003
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Baystate Medical CenterSpringfield, Massachusetts  01199
Cancer Institute of New JerseyNew Brunswick, New Jersey  08901
Iowa Methodist Medical CenterDes Moines, Iowa  50309
Iowa Lutheran HospitalDes Moines, Iowa  50316-2301
MetroHealth Medical CenterCleveland, Ohio  44109
Sibley Memorial HospitalWashington, District of Columbia  20016
North Colorado Medical CenterGreeley, Colorado  80631
McKee Medical CenterLoveland, Colorado  80539
University of New Mexico Cancer CenterAlbuquerque, New Mexico  87131-5636
Elkhart General HospitalElkhart, Indiana  46515
Parkland Memorial HospitalDallas, Texas  75235
Front Range Cancer SpecialistsFort Collins, Colorado  80528
Poudre Valley HospitalFort Collins, Colorado  80524
Beebe Medical CenterLewes, Delaware  19958
Memorial HospitalCarthage, Illinois  62321
Galesburg ClinicGalesburg, Illinois  61401
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McDonough District HospitalMacomb, Illinois  61455
BroMenn Regional Medical CenterNormal, Illinois  61761
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Perry Memorial HospitalPrinceton, Illinois  61356
Community Cancer Center of MonroeMonroe, Michigan  48162
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Mercy Hospital of TiffinTiffin, Ohio  44883
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Exempla Lutheran Medical CenterWheat Ridge, Colorado  80033
Eureka HospitalEureka, Illinois  61530
Mercy HospitalCoon Rapids, Minnesota  55433
Graham Hospital AssociationCanton, Illinois  61520
Saint Joseph Medical CenterJoliet, Illinois  60435
Trinity Medical CenterMoline, Illinois  61265-1291
Medical Oncology and Hematology AssociatesDes Moines, Iowa  50309
Bixby Medical CenterAdrian, Michigan  49221
Saint Joseph Mercy HospitalAnn Arbor, Michigan  48106
Fairview-Southdale HospitalEdina, Minnesota  55435
Abbott-Northwestern HospitalMinneapolis, Minnesota  55407
Regions HospitalSaint Paul, Minnesota  55101
Saint Francis Regional Medical CenterShakopee, Minnesota  55379
Rice Memorial HospitalWillmar, Minnesota  56201
Saint Luke's HospitalMaumee, Ohio  43537
Geisinger Medical GroupState College, Pennsylvania  16801
Swedish American HospitalRockford, Illinois  61104
Fisher-Titus Medical CenterNorwalk, Ohio  44857
Longmont United HospitalLongmont, Colorado  80501
Union Hospital of Cecil CountyElkton MD, Maryland  21921
Mayo Clinic in FloridaJacksonville, Florida  32224
Memorial Medical CenterSpringfield, Illinois  62781
University of PittsburghPittsburgh, Pennsylvania  15261
Hennepin County Medical CenterMinneapolis, Minnesota  
VA Palo Alto Health Care SystemPalo Alto, California  94304-1207
Saint Alphonsus Regional Medical CenterBoise, Idaho  83706
Emory UniversityAtlanta, Georgia  30322
Indiana University Medical CenterIndianapolis, Indiana  46202
Presbyterian - Saint Lukes Medical Center - Health OneDenver, Colorado  80218
University of Texas Southwestern Medical CenterDallas, Texas  
Flower HospitalSylvania, Ohio  43560-2197
Metro-Minnesota CCOPSt. Louis Park, Minnesota  
Tufts Medical CenterBoston, Massachusetts  02111
Lakeview HospitalStillwater, Minnesota  55082
Thomas Jefferson University HospitalPhiladelphia, Pennsylvania  19131
Decatur Memorial HospitalDecatur, Illinois  62526
Northern Indiana Cancer Research ConsortiumSouth Bend, Indiana  
Hematology Oncology AssociatesAlbuquerque, New Mexico  87106
Butler Memorial HospitalButler, Pennsylvania  16001
Littleton Adventist HospitalLittleton, Colorado  80122
Parker Adventist HospitalParker, Colorado  80138
New Ulm Medical CenterNew Ulm, Minnesota  56073
OSF Saint Francis Medical CenterPeoria, Illinois  61637
The Medical Center of AuroraAurora, Colorado  80012
Penrose-Saint Francis HealthcareColorado Springs, Colorado  80907
Saint Anthony Central HospitalDenver, Colorado  80204
Exempla Saint Joseph HospitalDenver, Colorado  80218
Colorado Cancer Research Program CCOPDenver, Colorado  80224-2522
Saint Mary's Hospital and Regional Medical CenterGrand Junction, Colorado  81502
Saint Mary Corwin Medical CenterPueblo, Colorado  81004
Saint Francis Hospital and Medical CenterHartford, Connecticut  06105
Veterans Administration Medical CenterDecatur, Georgia  30033
Saint Joseph's-Candler Health SystemSavannah, Georgia  31405
Rush - Copley Medical CenterAurora, Illinois  60504
John H Stroger Jr Hospital of Cook CountyChicago, Illinois  60612-3785
Evanston CCOP-NorthShore University HealthSystemEvanston, Illinois  60201
Community Cancer Center FoundationNormal, Illinois  61761
Ottawa Regional Hospital and Healthcare CenterOttawa, Illinois  61350
Pekin Cancer Treatment CenterPekin, Illinois  61554
Illinois Oncology Research Association CCOPPeoria, Illinois  61615
Illinois CancerCare-PeoriaPeoria, Illinois  61615
Illinois Valley HospitalPeru, Illinois  61354
Richard L. Roudebush Veterans Affairs Medical CenterIndianapolis, Indiana  46202
Wishard HospitalIndianapolis, Indiana  46202
Saint Anthony Memorial Health CenterMichigan City, Indiana  46360
McFarland ClinicAmes, Iowa  50010
Medical Oncology and Hematology Associates-West Des MoinesClive, Iowa  50325
Iowa Oncology Research Association CCOPDes Moines, Iowa  50309
Mercy Medical Center - Des MoinesDes Moines, Iowa  50314
Medical Oncology and Hematology Associates-Des MoinesDes Moines, Iowa  50309
Mercy Medical Center-Sioux CitySioux City, Iowa  51104
Saint Luke's Regional Medical CenterSioux City, Iowa  51104
Hickman Cancer CenterAdrian, Michigan  49221
Michigan Cancer Research Consortium Community Clinical Oncology ProgramAnn Arbor, Michigan  48106
Oakwood HospitalDearborn, Michigan  48123
Saint John Hospital and Medical CenterDetroit, Michigan  48236
Allegiance HealthJackson, Michigan  49201
Sparrow HospitalLansing, Michigan  48912
Saint Mary Mercy HospitalLivonia, Michigan  48154
Mercy Memorial HospitalMonroe, Michigan  48162
Saint Joseph Mercy OaklandPontiac, Michigan  48341-2985
Saint Joseph Mercy Port HuronPort Huron, Michigan  48060
Saint Mary's of MichiganSaginaw, Michigan  48601
Lakeland HospitalSt. Joseph, Michigan  49085
Saint John Macomb-Oakland HospitalWarren, Michigan  48093
Miller-Dwan HospitalDuluth, Minnesota  55805
Unity HospitalFridley, Minnesota  55432
Saint John's Hospital - HealtheastMaplewood, Minnesota  55109
Minnesota Oncology Hematology PA-MaplewoodMaplewood, Minnesota  55109
North Memorial Medical Health CenterRobbinsdale, Minnesota  55422
Park Nicollet Clinic - Saint Louis ParkSaint Louis Park, Minnesota  55416
Minnesota Oncology and Hematology PA-WoodburyWoodbury, Minnesota  55125
Nevada Cancer Research Foundation CCOPLas Vegas, Nevada  89106
Cooper Hospital University Medical CenterCamden, New Jersey  08103
Veterans Adminstration New Jersey Health Care SystemEast Orange, New Jersey  07018-1095
Memorial Medical Center - Las CrucesLas Cruces, New Mexico  88011
New York University Langone Medical CenterNew York, New York  10016
Hematology Oncology Center IncorporatedElyria, Ohio  44035
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North Coast Cancer CareSandusky, Ohio  44870
Toledo Community Hospital Oncology Program CCOPToledo, Ohio  43617
Mercy Cancer Center at Saint Anne Mercy HospitalToledo, Ohio  43623
University of ToledoToledo, Ohio  43614
Saint Vincent Mercy Medical CenterToledo, Ohio  43608
Geisinger Wyoming ValleyWilkes-Barre, Pennsylvania  18711
Fredericksburg Oncology IncFredericksburg, Virginia  22401
Saint Vincent HospitalGreen Bay, Wisconsin  54301
Bay Area Medical CenterMarinette, Wisconsin  54143
Oconomowoc Memorial Hospital-ProHealth Care IncOconomowoc, Wisconsin  53066-3896
Horizon Oncology CenterLafayette, Indiana  47905
The Memorial Hospital at EastonEaston, Maryland  21601
North Coast Cancer Care-ClydeClyde, Ohio  43410
Community Health Partners Regional Medical CenterElyria, Ohio  44035
Saint Mary Medical and Regional Cancer CenterLanghorne, Pennsylvania  19047
Holy Family Memorial HospitalManitowoc, Wisconsin  54221
Riverview HospitalWisconsin Rapids, Wisconsin  54494
Hinsdale Hematology Oncology Associates IncorporatedHinsdale, Illinois  60521
Saint Nicholas HospitalMadison, Wisconsin  53715
Central Indiana Cancer Centers - IndianapolisIndianapolis, Indiana  46227
Stanford University Hospitals and ClinicsStanford, California  94305
Siouxland Hematology Oncology AssociatesSioux City, Iowa  51101
Carle Foundation - Carle Cancer CenterUrbana, Illinois  61801
Marie Yeager Cancer CenterSaint Joseph, Michigan  49085
Eastern Cooperative Oncology GroupBoston, Massachusetts  02215
The Toledo Hospital/Toledo Children's HospitalToledo, Ohio  43606
Genesys Regional Medical Center-West Flint CampusFlint, Michigan  48532
Essentia Health Saint Joseph's Medical CenterBrainerd, Minnesota  56401
Essentia Health Duluth Clinic CCOPDuluth, Minnesota  55805
Essentia Health Saint Mary's Medical CenterDuluth, Minnesota  55805
Toledo Clinic Cancer Centers-OregonOregon, Ohio  43616
Geisinger Medical Center-Cancer Center HazeltonHazleton, Pennsylvania  18201
Community Howard Regional HealthKokomo, Indiana  46904
Indiana University Health La Porte HospitalLa Porte, Indiana  46350
Saint Joseph Regional Medical Center-MishawakaMishawaka, Indiana  46545-1470
Christiana Care Health System-Christiana HospitalNewark, Delaware  19718
IU Health Methodist HospitalIndianapolis, Indiana  46202
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Toledo Clinic Cancer Centers-MaumeeMaumee, Ohio  43537-1839
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PinnacleHealth Fox Chase Regional Cancer Center at Polyclinic HospitalHarrisburg, Pennsylvania  17110
Cancer Center of Western WisconsinNew Richmond, Wisconsin  54017