Safety and Efficacy Study of Enzalutamide Plus Leuprolide in Patients With Nonmetastatic Prostate Cancer (EMBARK)
Hormone Sensitive Prostate Cancer, Prostate Cancer, Cancer of the Prostate
About this trial
This is an interventional treatment trial for Hormone Sensitive Prostate Cancer
Eligibility Criteria
Inclusion Criteria:
- Histologically or cytologically confirmed adenocarcinoma of the prostate at initial biopsy, without neuroendocrine differentiation, signet cell, or small cell features;
- Prostate cancer initially treated by radical prostatectomy or radiotherapy (including brachytherapy) or both, with curative intent;
- PSA doubling time ≤ 9 months;
- Screening PSA by the central laboratory ≥ 1 ng/mL for patients who had radical prostatectomy (with or without radiotherapy) as primary treatment for prostate cancer and at least 2 ng/mL above the nadir for patients who had radiotherapy only as primary treatment for prostate cancer;
- Serum testosterone ≥ 150 ng/dL (5.2 nmol/L).
Exclusion Criteria:
- Prior or present evidence of distant metastatic disease as assessed by radiographic imaging;
- Prior hormonal therapy. Neoadjuvant/adjuvant therapy to treat prostate cancer ≤ 36 months in duration and ≥ 9 months before randomization, or a single dose or a short course (≤ 6 months) of hormonal therapy given for rising PSA ≥ 9 months before randomization is allowed.;
- Prior cytotoxic chemotherapy, aminoglutethimide, ketoconazole, abiraterone acetate, or enzalutamide for prostate cancer;
- Prior systemic biologic therapy, including immunotherapy, for prostate cancer;
- Major surgery within 4 weeks before randomization;
- Treatment with 5-α reductase inhibitors (finasteride, dutasteride) within 4 weeks of randomization;
- Known or suspected brain metastasis or active leptomeningeal disease;
- History of another invasive cancer within 3 years before screening, with the exception of fully treated cancers with a remote probability of recurrence
Sites / Locations
- University of Alabama at Birmingham
- University of Alabama at Birmingham, IDS Pharmacy
- University of Alabama at Birmingham
- Alaska Urological Institute dba Alaska Clinical Research Center
- Urological Associates of Southern Arizona, PC
- Tower Hematology Oncology Medical Group
- Cedars-Senai OCC Pharmacy
- Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute
- University of California, Irvine Medical Center
- Sutter Medical Group, Vascular & Varicose Vein Center
- Sutter Medical Group
- UC Davis Comprehensive Cancer Center
- University of California Davis Medical Center
- University of California, Davis, School of Medicine
- The Urology Center of Colorado
- Foothills Urology, P.C.
- Eastern Connecticut Hematology Oncology Associates
- Johns Hopkins Kimmel Cancer Center/ Sibley Infusion
- Lakeland Regional Health Hollis Cancer Center
- Emory University Hospital
- Investigational Drug Service
- The Emory Clinic
- Winship Cancer Institute, Emory University
- Northwestern Medical Group
- Northwestern Memorial Hospital
- First Urology, PSC
- The University of Kansas Hospital
- Kansas City Urology Care, PA
- The University of Kansas Cancer Center and Medical Pavilion
- The University of Kansas Cancer Center, Investigational Drug Services
- GU Research Network/Wichita Urology Group
- John Hopkins University Hospital
- Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
- The Sidney Kimmel Cancer Center at Johns Hopkins Hospital- Oncology Investigational Drug Services
- Chesapeake Urology Research Associates
- Comprehensive Urology - Macomb Office
- Comprehensive Urology - Royal Oak (Stephenson) office
- GU Research Network, LLC / Urology Cancer Center
- VA Lahontan Valley Outpatient Clinic
- Memorial Sloan Kettering Cancer Center Basking Ridge
- Memorial Sloan Kettering Cancer Center Commack
- Memorial Sloan Kettering Cancer Center Westchester
- Memorial Hospital
- Sidney Kimmel Center for Prostate and Urologic Cancers
- Premier Medical Group of the Hudson Valley PC
- Memorial Sloan Kettering Cancer Center Rockville Centre
- Associated Medical Professionals of New York, PLLC
- Memorial Sloan Kettering Cancer Center Nassau
- Duke Investigational Chemotherapy Services
- Duke Nuclear Medicine
- Duke University Medical Center
- Alliance Urology Specialists, PA
- TriState Urologic Services PSC Inc., dba The Urology Group
- Mercy Health Jewish Hospital
- Clinical Research Solutions
- Southwest Urology
- OU Medical Center Presbyterian Tower
- Stephenson Cancer Center
- Stephenson Cancer Center
- Oregon Imaging Center
- Oregon Urology Institute
- Urologic Consultants of SE PA
- Keystone Urology Specialists
- Lancaster Urology
- Thomas Jefferson University, Sidney Kimmel Cancer Center, Clinical Research Organization
- Jefferson Medical Oncology
- Jefferson Urology Associates
- Thomas Jefferson University Hospital, Bodine Buiding
- Thomas Jefferson University, Medical Oncology
- Thomas Jefferson University, Sidney Kimmel Cancer Center
- Carolina Urologic Research Center
- Vanderbilt Unversity Medical Center, Dept. of Urologic Surgery
- Vanderbilt Unversity Medical Center, The Urology Clinic
- Urology Clinics of North Texas, PLLC
- Houston Metro Urology
- Urology San Antonio Research
- Henrico Doctor's Hospital
- Virginia Urology
- Urology of Virginia, PLLC.
- Genesis Cancer Care NSW
- Lismore Base hospital
- Liverpool Hospital
- Macquarie University
- Genesis Cancer Care
- Port Macquarie Base Hospital
- GenesisCare North Shore
- The Tweed Hospital
- Australian Clinical Trials Pty Ltd
- Sydney Adventist Hospital
- Calvary Mater Newcastle
- Westmead Hospital
- Illawarra Cancer Care Centre
- Crown Princess Mary Cancer Centre
- Icon Cancer Care Wesley
- Icon Cancer Care Chermside
- Icon Cancer Care South Brisbane
- Icon Cancer Foundation
- Icon Cancer Centre Southport
- Royal Adelaide Hospital
- Box Hill Hospital
- Monash Medical Centre
- Austin Health
- Australian Urology Associates
- Sunshine Hospital
- Fiona Stanley Hospital
- Hospital Barmherzige Schwestern Linz
- Hospital Barmherzige Schwestern Linz, Department of Urology
- Ordensklinikum Linz GmbH
- Department of Nuclear Medicine and Endocrinology, University Hospital Salzburg, Austria
- Department of Radiology, University Hospital Salzburg, Austria
- Department of Urology,Paracelsus Medical University Salzburg
- AKH - Medizinische Universität Wien
- Department of Internal Medicine I, Medical university Vienna
- Hospital São Rafael S.A
- Liga Paranaense de Combate ao Cancer - Hospital Erasto Gaertner
- CITO - Centro Integrado de Terapia Onco-Hematologica - Hospital de Clinicas de Passo Fundo
- Hospital de Clinicas de Porto Alegre
- CLINIONCO - Clinica de Oncologia de Porto Alegre Ltda.
- Hospital Sao Lucas da PUCRS
- Fundacao Pio XII - Hospital de Cancer de Barretos
- Hospital das Clinicas da Faculdade de Ciencias Medicas da UNICAMP
- Centro de Estudos e Pesquisas de Hematologia e Oncologia - Faculdade de Medicina do ABC
- Oncosite - Centro de Pesquisa Clinica em Oncologia Ltda
- Prostate Cancer Centre
- Cross Cancer Institute
- Vancouver Prostate Centre
- Manitoba Prostate Centre CancerCare Manitoba
- Nova Scotia Health Authority
- The Male/Female Health and Research Centre, Royal Court Medical Centre
- Kingston General Hospital
- Centre for Applied Urological Research
- Hotel Dieu Hospital
- Urology Associates/ Urologic Medical Research
- London Health Sciences Centre - Victoria Hospital
- Sunnybrook Health Sciences Centre
- University Health Network - Princess Margaret Cancer Centre
- Urology South Shore Research
- Centre Hospitalier de l'Universite de Montreal
- McGill University Health Centre
- Ultra-Med Inc.
- CHU de Quebec - L'Hotel-Dieu de Quebec
- CHU de Quebec - L'Hotel-Dieu de Quebec - CRCEO
- Aarhus University Hospital
- Rigshospitalet - Copenhagen University Hospital
- Rigshospitalet - Copenhagen University Hospital
- Rigshospitalet, Dept of Radiology
- Odense University Hospital
- Vejle Sygehus
- Helsingin yliopistollinen keskussairaala
- Oulun yliopistollinen sairaala
- Satakunnan Keskussairaala
- Seinaejoen Keskussairaala
- Tampereen yliopistollinen sairaala
- ICO- site Paul Papin
- Clinique Pasteur - Lanroze Service Pharmacie
- Clinique Pasteur - Lanroze
- CHD Vendée
- CHRU de Lille - Hopital Claude Huriez
- ICM Val d'Aurelle
- CHU de Nantes - Hotel Dieu
- Hopital Saint-Louis
- Institut Mutualiste Montsouris
- CHP Saint-Gregoire
- ICO - site Rene Gauducheau
- Hia Begin
- Hopital Foch
- Institut Gustave Roussy
- Institut Gustave Roussy
- Farmacia, Azienda Socio Sanitaria Territoriale di Cremona
- Struttura Complessa di Oncologia, Azienda Socio Sanitaria Territoriale di Cremona
- UO di Radiologia, Azienda Socio Sanitaria Territoriale di Cremona
- UO di Oncologia,Ospedale Civile degli Infermi
- UO di Radiologia, Ospedale Civile degli Infermi
- UO di Oncologia, Ospedale Civile Umberto I
- Uo di Radiologia, Ospedale Civile Umberto I
- Laboratorio Farmaci Antiblastici, IRCCS Istituto
- U.O. Oncologia Medica, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
- UO Radiologia,IRCCS Istituto Scientifico Romagnolo Per lO Studio e la Cura dei Tumori (IRST)
- Istituto Nazionale Tumori Fondazione G. Pascale/Oncologia Medica A
- S.C.D.U. Oncologia Medica, A.O.U. San Luigi Gonzaga
- S.C.D.U. Radiodiagnostica, A.O.U. San Luigi Gonzaga
- Servizio di Farmacia, Ospedale Santa Maria delle Croci
- Servizio di Radiologia, Ospedale Santa Maria Delle Croci
- UO di Oncologia Medica, Ospedale Santa Maria delle Croci
- Farmacia Interna, Ospedale degli Infermi
- UO Oncologia, Ospedale degli Infermi
- Azienda Ospedaliera S, Camillo Forlanini, UOC per il governo clinico in Oncologia Medica,pad,Flajani
- U.O. di Oncologia Medica, Ospedale Santa Chiara
- U.O. Medicina Nucleare, Ospedale Santa Chiara
- U.O. Radiologia, Ospedale Santa Chiara
- Seoul National University Bundang Hospital
- Pusan National University Yangsan Hospital
- Chonnam National University Hwasun Hospital
- Gachon University Gil Medical Center
- Severance Hospital. Yonsei University Health System
- Asan Medical Center
- Gangnam Severance Hospital, Yonsei University Health System
- Samsung Medical Center
- VU Medical Centrum, Department of Urology
- Academisch Medisch Centrum
- Gelderse Vallei Ziekenhuis
- Catharina Ziekenhuis Eindhoven
- University Medical Centrum Groningen, Department Urologie
- Medisch Centrum Leeuwarden
- Maastricht University Medical Center, Department of Urology
- Antonius Ziekenhuis
- Uniwersyteckie Centrum Kliniczne Klinika Onkologii i Radioterapii
- Wojewodzki Szpital Specjalistyczny im. Janusza Korczaka w Slupsku Sp. z o. o.
- Wojewodzki Szpital Specjalistyczny im. Janusza Korczaka w Slupsku Sp. z o.o., Oddzial Urologiczny
- Kujawsko-Pomorskie Centrum Urologicznw Sp z o.o
- Centrum Medyczne Melita Medical
- EMC Instytut Medyczny Spolka Akcyjna
- Fakultna nemocnica s poliklinikou F.D.Roosevelta
- CUIMED, s.r.o., Urologicka ambulancia
- Vychodoslovensky onkologicky ustav, a.s.
- Univerzitna nemocnica Martin
- UROEXAM, spol. s r.o.
- MILAB
- Fakultna nemocnica s poliklinikou Zilina
- Althaia, Xarxa Assistencial Universitària de Manresa
- Hospital Universitari Son Espases
- Complejo Hospitalario Universitario de Santiago
- Hospital del Mar
- Hospital Clinic i Provincial de Barcelona, Dr. Antonio Alcaraz Asensio
- Hospital Universitario Puerta del Mar
- ICO Girona; Hospital Universitari de Girona Dr. Josep Trueta. Servicio de Oncologia
- Hospital Universitario de La Princesa
- Hospital General Universitario Gregorio Maranon. Servicio de Oncologia.
- Centro Oncologico MD Anderson International Espana
- Hospital Universitario Ramon Y Cajal
- Hospital Universitario 12 de Octubre
- Althaia, Xarxa Assistencial Universitària de Manresa
- Complejo Hospitalario Universitario de Orense
- Corporacio Sanitaria Parc Tauli
- Hospital Clinico Universitario de Salamanca
- Instituto Valenciano de Oncologia IVO
- Sahlgrenska Universitetssjukhuset, Sahlgrenska
- Skanes Universitetssjukhus
- Universitetssjukhuset Orebro
- Sodersjukhuset AB
- Karolinska Universitetssjukhuset Solna
- Norrlands Universitetssjukhus
- Norrlands Universitetssjukhus
- Akademiska Sjukhuset
- Kaohsiung Medical University Chung-Ho Memorial Hospital
- China Medical University Hospital
- Taichung Veterans General Hospital
- National Taiwan University Hospital
- Chang Gung Memorial Hospital, Linkou
- Ross Hall Hospital
- Royal Devon & Exeter Hospital
- Royal Free Hospital
- The Royal Marsden NHS Foundation Trust
- Cancer Centre, Queen Elizabeth Hospital
- University Hospitals Bristol NHS Foundation Trust
- Beatson West of Scotland Cancer Centre
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Experimental
Active Comparator
Enzalutamide plus leuprolide
Enzalutamide monotherapy
Leuprolide plus placebo
Enzalutamide (160 mg) administered as four 40-mg capsules by mouth once daily in combination with leuprolide administered as as a single intramuscular or subcutaneous injection once every 12 weeks
Enzalutamide (160 mg) administered as four 40-mg capsules by mouth once daily
Enzalutamide placebo (placebo) capsules (identical in appearance to enzalutamide) administered as 4 capsules by mouth once daily in combination with leuprolide administered as a single intramuscular or subcutaneous injection once every 12 weeks. The randomized blinded portion of the study has concluded following primary endpoint analyses. In the Open Label Period the placebo is no longer applicable in this study arm, and patients continue to receive leuprolide alone.