A Study of Apalutamide (ARN-509) in Men With Non-Metastatic Castration-Resistant Prostate Cancer
NCT ID: NCT01946204
Last Updated: 2025-11-12
Study Results
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View full resultsBasic Information
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ACTIVE_NOT_RECRUITING
PHASE3
1207 participants
INTERVENTIONAL
2013-10-14
2027-12-31
Brief Summary
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Detailed Description
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Phase 3 studies are performed after preliminary evidence suggesting effectiveness of the drug has been obtained in previous Phase 2 studies. These studies are intended to gather the additional information about effectiveness and safety that is needed to evaluate the overall benefit-risk relationship of the drug.
Study participants will take the oral investigational medication daily. One cycle of study treatment lasts 4 weeks or 28 days. The number of cycles will depend on how you and your cancer respond to the study medication.
In order for the researchers to evaluate and compare the study results, there are two different study groups. Study participants will be randomly (like flipping a coin) assigned to one of these groups:
* One group will receive their current treatment along with the investigational medication
* One group will receive their current medications along with a placebo
The investigational medication will be given to 2 out of every 3 study participants. Neither you nor the study staff will know which group you are in. However, in case of a medical emergency, your study doctor can quickly find out which treatment group you are in.
All participants will continue to receive their current treatment along with either the investigational medication or a placebo. The selections will be random, and you may remain on investigational treatment until your disease worsens, or until significant side effects occur or you can no longer tolerate treatment.
Conditions
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Keywords
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
TRIPLE
Study Groups
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Treatment Arm A: Apalutamide
Apalutamide
240 mg tablets administered by mouth on a continuous once daily dosing regimen
Treatment Arm B: Placebo
Placebo
Matched placebo tablets administered by mouth on a continuous once daily dosing regimen
Interventions
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Apalutamide
240 mg tablets administered by mouth on a continuous once daily dosing regimen
Placebo
Matched placebo tablets administered by mouth on a continuous once daily dosing regimen
Eligibility Criteria
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Inclusion Criteria
* 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
* 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
18 Years
MALE
No
Sponsors
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Aragon Pharmaceuticals, Inc.
INDUSTRY
Responsible Party
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Principal Investigators
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Aragon Pharmaceuticals, Inc. Clinical Trial
Role: STUDY_DIRECTOR
Aragon Pharmaceuticals, Inc.
Locations
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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 D.C., 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
Sarasota, Florida, United States
St. Petersburg, 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 Township, New Jersey, United States
Albuquerque, New Mexico, United States
Albany, 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
The Bronx, 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
Vienna, , Austria
Brussels, , Belgium
Ghent, , Belgium
Kortrijk, , Belgium
Leuven, , Belgium
Liège, , Belgium
Ottignies, , Belgium
Calgary, Alberta, Canada
Edmonton, Alberta, Canada
Abbotsford, British Columbia, Canada
Kelowna, 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
Québec, Quebec, Canada
Sherbrooke, Quebec, Canada
Liberec, , Czechia
Olomouc, , Czechia
Opava, , Czechia
Pilsen, , Czechia
Prague, , Czechia
Aalborg C, , Denmark
Copenhagen, , Denmark
Odense, , Denmark
Roskilde, , Denmark
Helsinki, , Finland
Oulu, , Finland
Seinäjoki, , Finland
Tampere, , Finland
Turku, , Finland
Angers, , France
Besançon, , France
Bordeaux, , France
Caen Cédex 05, , France
Clermont-Ferrand, , France
Hyers, , France
La Roche-sur-Yon, , France
Le Mans, , France
Lille Cedex N/a, , France
Lyon, , France
Marseille, , France
Nice, , France
Nîmes, , France
Paris, , France
Reims, , France
Rennes, , France
Rouen, , France
Saint-Grégoire, , France
Saint-Herblain, , France
Strasbourg, , France
Suresnes, , France
Tours, , France
Vandœuvre-lès-Nancy, , France
Aachen, , Germany
Bergisch Gladbach, , Germany
Berlin, , Germany
Braunschweig, , Germany
Cologne, , Germany
Duisburg, , Germany
Emmendingen, , Germany
Frankfurt am Main, , Germany
Göttingen, , Germany
Greifswald, , Germany
Hamburg, , Germany
Hanover, , Germany
Heidelberg, , Germany
Heinsberg, , Germany
Homburg/Saar, , Germany
Jena, , Germany
Kiel, , Germany
Kirchheim unter Teck, , Germany
Magdeburg, , Germany
Mainz, , Germany
Mannheim, , Germany
Marburg, , Germany
Mettmann, , Germany
Müllheim, , Germany
Münster, , Germany
Nürtingen, , 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
Ẕerifin, , Israel
Akita, , Japan
Fukuoka, , 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, , Japan
Ōsaka-sayama, , Japan
Sagamihara, , Japan
Sakura, , Japan
Sapporo, , Japan
Shinjuku-Ku, , Japan
Tokushima, , Japan
Tokyo, , Japan
Ube, , Japan
Wakayama, , Japan
Yokohama, , Japan
Alkmaar, , Netherlands
Eindhoven, , Netherlands
Hoofddorp, , Netherlands
Leidschendam, , Netherlands
Nijmegen, , Netherlands
Rotterdam, , Netherlands
Auckland, , New Zealand
Christchurch, , New Zealand
Hamilton, , New Zealand
Nelson, , 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
Warsaw, , Poland
Wroclaw, , Poland
Baia Mare, , Romania
Brasov, , Romania
Bucharest, , Romania
Cluj-Napoca, , Romania
Târgu Mureş, , Romania
Barnaul, , Russia
Ivanovo, , Russia
Moscow, , Russia
Obninsk, , Russia
Omsk, , Russia
Ryazan, , Russia
Saint Petersburg, , Russia
Ufa, , Russia
Yaroslavl, , Russia
Yekaterinburg, , Russia
Banská Bystrica, , Slovakia
Bratislava, , Slovakia
Martin, , Slovakia
Nitra, , Slovakia
Trenčín, , Slovakia
Daegu, , South Korea
Gwangju, , South Korea
Pusan, , South Korea
Seongnam, , South Korea
Seoul, , South Korea
A Coruña, , Spain
Badalona, , Spain
Barcelona, , Spain
Castellon, , Spain
Girona, , Spain
Guadalajara, , Spain
Jerez de la Frontera, , Spain
Las Palmas de Gran Canaria, , Spain
Madrid, , Spain
Málaga, , Spain
Murcia, , Spain
Palma de Mallorca, , Spain
Pamplona, , Spain
Sabadell, , Spain
Salamanca, , Spain
San Sebastián de los Reyes, , Spain
Santander, , Spain
Seville, , Spain
Valencia, , Spain
Gothenburg, , Sweden
Örebro, , Sweden
Stockholm, , Sweden
Umeå, , Sweden
Uppsala, , Sweden
Kaohsiung City, , Taiwan
Taichung, , Taiwan
Taipei, , Taiwan
Taoyuan, , 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
Metropolitan Borough of Wirral, , United Kingdom
Nottingham, , United Kingdom
Plymouth, , United Kingdom
Southampton, , United Kingdom
Surrey, , United Kingdom
Swansea, , United Kingdom
Wolverhampton, , United Kingdom
Countries
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References
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Ni X, Sui J, Wang B, Wang H, Freedland SJ, Ye D, Zhu Y. Lower Testosterone Level and Metastases-Free Survival in Patients With Nonmetastatic Castration-Resistant Prostate Cancer Treated With Novel Antiandrogens: A Post Hoc Analysis of SPARTAN and ARAMIS. J Urol. 2025 Jul;214(1):10-17. doi: 10.1097/JU.0000000000004545. Epub 2025 Mar 25.
Feng FY, Smith MR, Saad F, Mobadersany P, Tian SK, Yip SSF, Greshock J, Khan N, Yu MK, McCarthy S, Brookman-May SD, Bourla AB, Todorovic T, Yamashita R, Huang HC, Royce TJ, Showalter TN, Griffin J, Mitani A, Esteva A, Small EJ. Digital Pathology-Based Multimodal Artificial Intelligence Scores and Outcomes in a Randomized Phase III Trial in Men With Nonmetastatic Castration-Resistant Prostate Cancer. JCO Precis Oncol. 2025 Jan;9:e2400653. doi: 10.1200/PO-24-00653. Epub 2025 Jan 31.
Roy S, Malone S, Wing K, Chowdhury S, Kishan AU, Sun Y, Wallis CJD, Mohamad O, Jia AY, Swami U, Zaorsky NG, Morgan SC, Ong M, Agarwal N, Spratt DE, Small EJ, Saad F. Prior Local Therapy and First-Line Apalutamide in Patients With Nonmetastatic Castration-Resistant Prostate Cancer: A Secondary Analysis of the SPARTAN Randomized Clinical Trial. JAMA Netw Open. 2024 Oct 1;7(10):e2439434. doi: 10.1001/jamanetworkopen.2024.39434.
Karsh LI, Bevans KB, Saad F, Chung BH, Oudard S, Brookman-May SD, McCarthy SA, Smith MR, Chi KN, Small EJ, Agarwal N. Prostate-specific antigen and health-related quality of life in individuals with advanced prostate cancer treated with apalutamide: a plain language summary of the SPARTAN and TITAN studies. Future Oncol. 2024;20(35):2689-2698. doi: 10.1080/14796694.2024.2384257. Epub 2024 Aug 20.
Shen J, Chowdhury S, Agarwal N, Karsh LI, Oudard S, Gartrell BA, Feyerabend S, Saad F, Pieczonka CM, Chi KN, Brookman-May SD, Rooney B, Bhaumik A, McCarthy SA, Bevans KB, Mundle SD, Small EJ, Smith MR, Graff JN. Apalutamide efficacy, safety and wellbeing in older patients with advanced prostate cancer from Phase 3 randomised clinical studies TITAN and SPARTAN. Br J Cancer. 2024 Jan;130(1):73-81. doi: 10.1038/s41416-023-02492-8. Epub 2023 Nov 11.
Pollock Y, Smith MR, Saad F, Chowdhury S, Oudard S, Hadaschik B, Olmos D, Lee JY, Uemura H, Bhaumik A, Londhe A, Rooney B, Brookman-May SD, De Porre P, Mundle SD, Small EJ. Clinical characteristics associated with falls in patients with non-metastatic castration-resistant prostate cancer treated with apalutamide. Prostate Cancer Prostatic Dis. 2023 Mar;26(1):156-161. doi: 10.1038/s41391-022-00592-9. Epub 2022 Oct 8.
Chowdhury S, Oudard S, Uemura H, Joniau S, Dearden L, Capone C, Van Sanden S, Diels J, Hadaschik BA. Apalutamide Compared with Darolutamide for the Treatment of Non-metastatic Castration-Resistant Prostate Cancer: Efficacy and Tolerability in a Matching-Adjusted Indirect Comparison. Adv Ther. 2022 Jan;39(1):518-531. doi: 10.1007/s12325-021-01885-6. Epub 2021 Nov 19.
Uemura H, Koroki Y, Iwaki Y, Imanaka K, Kambara T, Lopez-Gitlitz A, Smith A, Uemura H. Skin rash following Administration of Apalutamide in Japanese patients with Advanced Prostate Cancer: an integrated analysis of the phase 3 SPARTAN and TITAN studies and a phase 1 open-label study. BMC Urol. 2020 Sep 2;20(1):139. doi: 10.1186/s12894-020-00689-0.
Smith MR, Mehra M, Nair S, Lawson J, Small EJ. Relationship Between Metastasis-free Survival and Overall Survival in Patients With Nonmetastatic Castration-resistant Prostate Cancer. Clin Genitourin Cancer. 2020 Apr;18(2):e180-e189. doi: 10.1016/j.clgc.2019.10.030. Epub 2019 Nov 6.
Saad F, Cella D, Basch E, Hadaschik BA, Mainwaring PN, Oudard S, Graff JN, McQuarrie K, Li S, Hudgens S, Lawson J, Lopez-Gitlitz A, Yu MK, Smith MR, Small EJ. Effect of apalutamide on health-related quality of life in patients with non-metastatic castration-resistant prostate cancer: an analysis of the SPARTAN randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2018 Oct;19(10):1404-1416. doi: 10.1016/S1470-2045(18)30456-X. Epub 2018 Sep 10.
Smith MR, Saad F, Chowdhury S, Oudard S, Hadaschik BA, Graff JN, Olmos D, Mainwaring PN, Lee JY, Uemura H, Lopez-Gitlitz A, Trudel GC, Espina BM, Shu Y, Park YC, Rackoff WR, Yu MK, Small EJ; SPARTAN Investigators. Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer. N Engl J Med. 2018 Apr 12;378(15):1408-1418. doi: 10.1056/NEJMoa1715546. Epub 2018 Feb 8.
Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Other Identifiers
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ARN-509-003; 56021927PCR1007
Identifier Type: OTHER
Identifier Source: secondary_id
2012-004322-24
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
CR102931
Identifier Type: -
Identifier Source: org_study_id