A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase III Study of ARN-509 in Men With Non-Metastatic (M0) Castration-Resistant Prostate Cancer

Condition: Prostatic Neoplasms

Intervention:

• Drug: Apalutamide
• Drug: Placebo

Purpose: The purpose of this study is to evaluate the efficacy and safety of apalutamide in adult men with high-risk non-metastatic castration-resistant prostate cancer.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT01946204

Sponsor: Aragon Pharmaceuticals, Inc.

Primary Outcome Measures:

• Measure: Metastasis-Free Survival (MFS) by Blinded Independent Central Review (BICR)
• Time Frame: Up to approximately 43 Months
• Safety Issue:

Secondary Outcome Measures:

• Measure: Time to Metastasis (TTM)
• Time Frame: Up to approximately 43 Months
• Safety Issue:
• Measure: Progression-free Survival (PFS)
• Time Frame: Up to approximately 43 Months
• Safety Issue:
• Measure: Time to Symptomatic Progression
• Time Frame: Up to approximately 43 Months
• Safety Issue:
• Measure: Overall Survival
• Time Frame: Up to approximately 43 months
• Safety Issue:
• Measure: Time to Initiation of Cytotoxic Chemotherapy
• Time Frame: Up to approximately 43 months
• Safety Issue:

Estimated Enrollment: 1207

Study Start Date: October 14, 2013

Phase: Phase 3

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: Male

Inclusion Criteria:

• Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features with high risk for development of metastases, defined as prostate-specific antigen doubling time (PSADT) less than or equal to (<=) 10 months. PSADT is calculated using at least 3 prostate-specific antigen (PSA) values obtained during continuous ADT (androgen deprivation therapy)
• Castration-resistant prostate cancer demonstrated during continuous ADT, defined as 3 PSA rises, at least 1 week apart, with the last PSA greater than (>) 2 nanogram per milliliter (ng/mL)
• Maintain castrate levels of testosterone within 4 weeks prior to randomization and throughout the study
• Patients currently receiving bone loss prevention treatment with bone-sparing agents must be on stable doses for at least 4 weeks prior to randomization
• Patients who received a first generation anti-androgen (for example, bicalutamide, flutamide, nilutamide) must have at least a 4-week washout prior to randomization AND must show continuing disease (PSA) progression (an increase in PSA) after washout
• At least 4 weeks must have elapsed from the use of 5-alpha reductase inhibitors, estrogens, and any other anti-cancer therapy prior to randomization
• At least 4 weeks must have elapsed from major surgery or radiation therapy prior to randomization
• Eastern Cooperative Oncology Group Performance Status 0 or 1
• Resolution of all acute toxic effects of prior therapy or surgical procedure to Grade <= 1 or baseline prior to randomization
• Adequate organ function according to protocol-defined criteria
• Administration of growth factors or blood transfusions will not be allowed within 4 weeks of the hematology labs required to confirm eligibility

Exclusion Criteria:

• Presence of confirmed distant metastases, including central nervous system and vertebral or meningeal involvement
• Symptomatic local or regional disease requiring medical intervention
• Prior treatment with second generation anti-androgens
• Prior treatment with CYP17 inhibitors
• Prior treatment with radiopharmaceutical agents, or any other investigational agent for non-metastatic castration-resistant prostate cancer
• Prior chemotherapy for prostate cancer except if administered in the adjuvant/neoadjuvant setting
• History of seizure or condition that may pre-dispose to seizure
• Concurrent therapy with protocol-defined excluded medications
• History or evidence of any of the following conditions: any prior malignancy (other than adequately treated basal cell or squamous cell skin cancer, superficial bladder cancer, or any other cancer in situ currently in complete remission) within 5 years prior to randomization; severe/unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events, or clinically significant ventricular arrhythmias within 6 months prior to randomization; uncontrolled hypertension; gastrointestinal disorder affecting absorption; active infection; and, any other condition that, in the opinion of the investigator, would impair the patient’s ability to comply with study procedures

Locations:

• Birmingham Alabama United States

• Anchorage Alaska United States

• Chandler Arizona United States

• Tucson Arizona United States

• Duarte California United States

• Fullerton California United States

• Laguna Woods California United States

• Los Angeles California United States

• Orange California United States

• Roseville California United States

• Sacramento California United States

• San Bernardino California United States

• San Diego California United States

• San Francisco California United States

• Santa Monica California United States

• Sherman Oaks California United States

• Stanford California United States

• Tarzana California United States

• Torrance California United States

• Denver Colorado United States

• Englewood Colorado United States

• Glenwood Springs Colorado United States

• Grand Junction Colorado United States

• Washington District of Columbia United States

• Aventura Florida United States

• Boca Raton Florida United States

• Bradenton Florida United States

• Daytona Beach Florida United States

• Fort Myers Florida United States

• Hialeah Florida United States

• Jacksonville Florida United States

• Miami Florida United States

• New Port Richey Florida United States

• Orlando Florida United States

• Saint Petersburg Florida United States

• Sarasota Florida United States

• Wellington Florida United States

• Meridian Idaho United States

• Chicago Illinois United States

• Decatur Illinois United States

• Maywood Illinois United States

• Melrose Park Illinois United States

• Carmel Indiana United States

• Jeffersonville Indiana United States

• Muncie Indiana United States

• West Des Moines Iowa United States

• Westwood Kansas United States

• Wichita Kansas United States

• Metairie Louisiana United States

• New Orleans Louisiana United States

• Annapolis Maryland United States

• Baltimore Maryland United States

• Rockville Maryland United States

• Towson Maryland United States

• Boston Massachusetts United States

• Detroit Michigan United States

• Lansing Michigan United States

• Minneapolis Michigan United States

• Royal Oak Michigan United States

• Duluth Minnesota United States

• Bay Saint Louis Mississippi United States

• Southaven Mississippi United States

• Kansas City Missouri United States

• Missoula Montana United States

• Omaha Nebraska United States

• Las Vegas Nevada United States

• Hooksett New Hampshire United States

• Hackensack New Jersey United States

• Lawrenceville New Jersey United States

• Morristown New Jersey United States

• Mount Laurel New Jersey United States

• New Brunswick New Jersey United States

• Voorhees New Jersey United States

• Albuquerque New Mexico United States

• Albany New York United States

• Bronx New York United States

• Mineola New York United States

• New York New York United States

• Oneida New York United States

• Poughkeepsie New York United States

• Syracuse New York United States

• Concord North Carolina United States

• Greensboro North Carolina United States

• Greenville North Carolina United States

• Salisbury North Carolina United States

• Winston-Salem North Carolina United States

• Cincinnati Ohio United States

• Cleveland Ohio United States

• Middleburg Heights Ohio United States

• Middletown Ohio United States

• Bend Oregon United States

• Portland Oregon United States

• Tualatin Oregon United States

• Bala-Cynwyd Pennsylvania United States

• Bryn Mawr Pennsylvania United States

• Lancaster Pennsylvania United States

• Philadelphia Pennsylvania United States

• Pittsburgh Pennsylvania United States

• Warwick Rhode Island United States

• Charleston South Carolina United States

• Greenville South Carolina United States

• Myrtle Beach South Carolina United States

• West Columbia South Carolina United States

• Memphis Tennessee United States

• Nashville Tennessee United States

• Abilene Texas United States

• Amarillo Texas United States

• Dallas Texas United States

• Fort Sam Houston Texas United States

• Houston Texas United States

• McAllen Texas United States

• San Antonio Texas United States

• Norfolk Virginia United States

• Richmond Virginia United States

• Virginia Beach Virginia United States

• Burien Washington United States

• Edmonds Washington United States

• Seattle Washington United States

• Tacoma Washington United States

• Green Bay Wisconsin United States

• Madison Wisconsin United States

• Milwaukee Wisconsin United States

• Adelaide Australia

• Box Hill Australia

• Camperdown Australia

• Darlinghurst Australia

• Geelong Australia

• Gosford Australia

• Hobart Australia

• Kogarah Australia

• Liverpool Australia

• Melbourne Australia

• Nedlands Australia

• Parkville Australia

• South Woodville Australia

• Southport Australia

• Sydney Australia

• Tweed Heads Australia

• Wollongong Australia

• Graz Austria

• Innsbruck Austria

• Linz Austria

• Wien Austria

• Brussels Belgium

• Brussel Belgium

• Gent Belgium

• Kortrijk Belgium

• Leuven Belgium

• Liege Belgium

• Ottignies Belgium

• Calgary Alberta Canada

• Edmonton Alberta Canada

• Abbotsford British Columbia Canada

• Vancouver British Columbia Canada

• Victoria British Columbia Canada

• Moncton New Brunswick Canada

• Saint John New Brunswick Canada

• Halifax Nova Scotia Canada

• Barrie Ontario Canada

• Brampton Ontario Canada

• Brantford Ontario Canada

• Hamilton Ontario Canada

• London Ontario Canada

• North York Ontario Canada

• Oakville Ontario Canada

• Ottawa Ontario Canada

• Owen Sound Ontario Canada

• Toronto Ontario Canada

• Gatineau Quebec Canada

• Granby Quebec Canada

• Greenfield Park Quebec Canada

• Laval Quebec Canada

• Montreal Quebec Canada

• Pointe-Claire Quebec Canada

• Sherbrooke Quebec Canada

• Kelowna Canada

• Montrel Canada

• Quebec Canada

• Toronto Canada

• Liberec Czechia

• Olomouc Czechia

• Opava Czechia

• Plzen Czechia

• Praha 2 Czechia

• Praha 4 Czechia

• Praha 5 Czechia

• Praha Czechia

• Aalborg C Denmark

• Copenhagen Denmark

• Odense N/a Denmark

• Roskilde Denmark

• Helsinki Finland

• Oulu Finland

• Seinäjoki Finland

• Tampere Finland

• Turku Finland

• Angers Cedex 9 France

• Angers France

• Besancon France

• Bordeaux France

• Caen Cédex 05 France

• Clermont Ferrand France

• Hyers France

• La Roche sur Yon Cedex 9 France

• Le Mans France

• Lille Cedex N/a France

• Lyon France

• Marseille cedex 5 France

• Marseille Cedex 9 France

• Nice Cedex 2 France

• Nîmes Cedex 9 France

• Paris 75 France

• Paris Cedex 15 France

• Paris France

• Reims Cedex France

• Rennes Cedex France

• Rouen France

• Saint Gregoire France

• Saint Herblain France

• Strasbourg France

• Suresnes France

• Tours, Cedex 9 France

• Vandoeuvre Les Nancy Cedex France

• Aachen Germany

• Bergisch Gladbach Germany

• Berlin Germany

• Braunschweig Germany

• Duisburg Germany

• Emmendingen Germany

• Frankfurt / Main Germany

• Greifswald Germany

• Göttingen Germany

• Hamburg Germany

• Hannover Germany

• Heidelberg Germany

• Heinsberg Germany

• Homburg/Saar Germany

• Jena Germany

• Kiel Germany

• Kirchheim unter Teck Germany

• Köln Germany

• Magdeburg Germany

• Mainz Germany

• Mannheim Germany

• Marburg Germany

• Mettmann Germany

• Müllheim Germany

• Münster Germany

• Nuertingen Germany

• Regensburg Germany

• Rostock Germany

• Tübingen Germany

• Weiden Germany

• Wilhelmshaven Germany

• Wuppertan Germany

• Zirndorf Germany

• Budapest Hungary

• Miskolc Hungary

• Nyíregyhá Hungary

• Sopron Hungary

• Szentes Hungary

• Haifa Israel

• Jeruselem Israel

• Kfar-Saba Israel

• Petah-Tikva Israel

• Ramat Gan Israel

• Tel Aviv Israel

• Zerifin Israel

• Akita Japan

• Fukuoka-shi Japan

• Gifu Japan

• Hakodate Japan

• Hiroshima Japan

• Hokkaido Japan

• Kanazawa Japan

• Kashiwa Japan

• Kita-Gun Japan

• Kobe Japan

• Koshigaya Japan

• Kumamoto Japan

• Kurume Japan

• Matsuyama Japan

• Nagano Japan

• Nagasaki Japan

• Nagoya Japan

• Niigata Japan

• Osaka-Sayama Japan

• Osaka Japan

• Sagamihara Japan

• Sakura Japan

• Sapporo Japan

• Shinjuku-Ku Japan

• Tokushima Japan

• Tokyo Japan

• Wakayama Japan

• Yokohama Japan

• Daegu Korea, Republic of

• Gwangju-si Korea, Republic of

• Pusan Korea, Republic of

• Seongnam Korea, Republic of

• Seoul Korea, Republic of

• Alkmaar Netherlands

• Eindhoven Netherlands

• Hoofddorp Netherlands

• Leidschendam Netherlands

• Nijmegen Netherlands

• Rotterdam Netherlands

• Auckland New Zealand

• Christchurch New Zealand

• Hamilton New Zealand

• Nelson City New Zealand

• Tauranga New Zealand

• Whangarei New Zealand

• Nordbyhagen Norway

• Bialystok Poland

• Bydgoszcz Poland

• Gdansk Poland

• Kutno Poland

• Lodz Poland

• Poznan Poland

• Szczecin Poland

• Torun Poland

• Warszawa Poland

• Wroclaw Poland

• Baia Mare Romania

• Brasov Romania

• Bucharest Romania

• Cluj- Napoca Romania

• Targu Mures Romania

• Barnaul Russian Federation

• Ekaterinburg Russian Federation

• Ivanovo Russian Federation

• Moscow Russian Federation

• Obninsk, Kaluga Region Russian Federation

• Omsk Russian Federation

• Ryazan Russian Federation

• Saint Petersburg Russian Federation

• St. Petersburg Russian Federation

• Ufa Russian Federation

• Yaroslavl Russian Federation

• Banska Bystrica Slovakia

• Bratislava Slovakia

• Martin Slovakia

• Nitra Slovakia

• Trenčín Slovakia

• Badalona Spain

• Barcelona Spain

• Castellon Spain

• Coruña Spain

• Girona Spain

• Guadalajara Spain

• Jerez de la Frontera Spain

• Las Palmas De Gran Canaria Spain

• Madrid Spain

• Murcia Spain

• Málaga Spain

• Palma de Mallorca Spain

• Pamplona Spain

• Sabadell Spain

• Salamanca Spain

• San Sebastian de los Reyes Spain

• Santander Spain

• Sevilla N/a Spain

• Sevilla Spain

• Valencia Spain

• Goteborg Sweden

• Stockholm Sweden

• Umea Sweden

• Uppsala Sweden

• Örebro Sweden

• Kaohsiung Taiwan

• Taichung Taiwan

• Taipei Taiwan

• Taoyuan County Taiwan

• Blackburn United Kingdom

• Cambridge United Kingdom

• Cardiff United Kingdom

• Dundee United Kingdom

• Glasgow United Kingdom

• Guildford United Kingdom

• Leeds United Kingdom

• London United Kingdom

• Maidstone United Kingdom

• Nottingham United Kingdom

• Plymouth United Kingdom

• Southampton United Kingdom

• Surrey United Kingdom

• Swansea United Kingdom

• Wirral United Kingdom

• Wolverhampton United Kingdom

View trial on ClinicalTrials.gov