A Study of Apalutamide (JNJ-56021927, ARN-509) Plus Androgen Deprivation Therapy (ADT) Versus ADT in Participants With mHSPC
TITAN
A Phase 3 Randomized, Placebo-controlled, Double-blind Study of Apalutamide Plus Androgen Deprivation Therapy (ADT) Versus ADT in Subjects With Metastatic Hormone-sensitive Prostate Cancer (mHSPC)
3 other identifiers
interventional
1,052
22 countries
220
Brief Summary
The purpose of this study is to determine if the addition of apalutamide to ADT provides superior efficacy in improving radiographic progression-free survival (rPFS) or overall survival (OS) for participants with mHSPC.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3 prostate-cancer
Started Nov 2015
Longer than P75 for phase_3 prostate-cancer
220 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 1, 2015
CompletedFirst Posted
Study publicly available on registry
July 3, 2015
CompletedStudy Start
First participant enrolled
November 27, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 7, 2020
CompletedResults Posted
Study results publicly available
January 18, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
December 31, 2027
ExpectedApril 13, 2026
April 1, 2026
4.8 years
July 1, 2015
September 6, 2021
April 9, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Radiographic Progression-free Survival (rPFS)
rPFS as assessed by the investigator was defined as the duration from the date of randomization to the date of first documentation of radiographic progressive disease or death due to any cause, whichever occurred first. Radiographic progressive disease was defined as progression of soft tissue lesions measured by computed tomography (CT) or magnetic resonance imaging (MRI) as defined by modified Response evaluation criteria in solid tumors (RECIST) 1.1.
Up to 35 months
Overall Survival (OS)
OS was defined as the time from date of randomization to date of death from any cause.
Up to 57 months
Secondary Outcomes (4)
Time to Initiation of Cytotoxic Chemotherapy
Up to 57 months
Time to Pain Progression
Up to 57 months
Time to Chronic Opioid Use
Up to 57 months
Time to Skeletal-related Event (SRE)
Up to 57 months
Study Arms (2)
Apalutamide plus ADT
EXPERIMENTALParticipants will receive apalutamide 240 milligram (mg) (4X 60 mg tablets) with ADT.
Placebo plus ADT
EXPERIMENTALParticipants will receive matching Placebo with ADT.
Interventions
Participants will receive apalutamide 240 mg (4 x 60 mg) tablets orally once daily in each 28 day treatment cycles.
Participants will receive Placebo orally once daily in each 28 day treatment cycles.
All participants will receive and remain on a stable regimen of ADT (gonadotropin releasing hormone analog \[GnRHa\] or surgical castration). The choice of the GnRHa (agonist or antagonist) will be at discretion of the Investigator. Dosing (dose and frequency of administration) will be consistent with the prescribing information.
Eligibility Criteria
You may qualify if:
- Diagnosis of prostate adenocarcinoma as confirmed by the investigator
- Metastatic disease documented by greater than or equal to (\>=) 1 bone lesions on 99mTc bone scan. Participants with a single bone lesion must have confirmation of bone metastasis by computed tomography (CT) or magnetic resonance imaging (MRI)
- Eastern Cooperative Oncology Group Performance Status (ECOG PS) grade of 0 or 1
- Participants who received docetaxel treatment must meet the following criteria: a) Received a maximum of 6 cycles of docetaxel therapy for mHSPC; b) Received the last dose of docetaxel \<=2 months prior to randomization; c) Maintained a response to docetaxel of stable disease or better, by investigator assessment of imaging and PSA, prior to randomization
- Other allowed prior treatment for mHSPC: a) Maximum of 1 course of radiation or surgical intervention; radiation therapy for metastatic lesions must be completed prior to randomization; b) Less than or equal to (\<=) 6 months of ADT prior to randomization
- Allowed prior treatments for localized prostate cancer (all treatments must have been completed \>= 1 year prior to randomization) a) \<= 3 years total of ADT; b) All other forms of prior therapies including radiation therapy, prostatectomy,lymph node dissection, and systemic therapies
You may not qualify if:
- Pathological finding consistent with small cell, ductal or neuroendocrine carcinoma of the prostate
- Known brain metastases
- Lymph nodes as only sites of metastases
- Visceral (ie, liver or lung) metastases as only sites of metastases
- Other prior malignancy less than or equal to 5 years prior to randomization with the exception of squamous or basal cell skin carcinoma or non-invasive superficial bladder cancer
- Prior treatment with other next generation anti-androgens or other CYP17 inhibitors, immunotherapy or radiopharmaceutical agents for prostate cancer
- History of seizures or medications known to lower seizure threshold
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (220)
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Homewood, Alabama, United States
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Tucson, Arizona, United States
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San Bernardino, California, United States
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San Diego, California, United States
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Denver, Colorado, United States
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Norwalk, Connecticut, United States
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Fort Myers, Florida, United States
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Chicago, Illinois, United States
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Fort Wayne, Indiana, United States
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Jeffersonville, Indiana, United States
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New Orleans, Louisiana, United States
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Baltimore, Maryland, United States
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Rockville, Maryland, United States
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Lansing, Michigan, United States
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Troy, Michigan, United States
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Omaha, Nebraska, United States
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Las Vegas, Nevada, United States
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Brooklyn, New York, United States
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Poughkeepsie, New York, United States
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Syracuse, New York, United States
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The Bronx, New York, United States
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Raleigh, North Carolina, United States
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Salisbury, North Carolina, United States
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Cleveland, Ohio, United States
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Middleburg Heights, Ohio, United States
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Springfield, Oregon, United States
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Bala-Cynwyd, Pennsylvania, United States
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Bryn Mawr, Pennsylvania, United States
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Lancaster, Pennsylvania, United States
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Charleston, South Carolina, United States
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Nashville, Tennessee, United States
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Dallas, Texas, United States
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Houston, Texas, United States
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San Antonio, Texas, United States
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Richmond, Virginia, United States
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Virginia Beach, Virginia, United States
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Burien, Washington, United States
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Spokane, Washington, United States
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Milwaukee, Wisconsin, United States
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Berazategui, Argentina
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Buenos Aires, Argentina
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C.a.b.a., Argentina
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Capital Federal, Argentina
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Ciudad Automoma Buenos Aires, Argentina
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Ciudad de Buenos Aires, Argentina
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Córdoba, Argentina
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La Plata, Argentina
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Pergamino, Argentina
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Rosario, Argentina
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San Miguel de Tucumán, Argentina
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San Salvador de Jujuy, Argentina
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Albury, Australia
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Elizabeth Vale, Australia
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Kogarah, Australia
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Port Macquarie, Australia
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South Brisbane, Australia
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St Leonards, Australia
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Barretos, Brazil
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Florianópolis, Brazil
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Goiânia, Brazil
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Ijuí, Brazil
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Natal, Brazil
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Ribeirão Preto, Brazil
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Rio de Janeiro, Brazil
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Salvador, Brazil
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Santo André, Brazil
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São Paulo, Brazil
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Sorocaba, Brazil
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Calgary, Alberta, Canada
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Vancouver, British Columbia, Canada
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Hamilton, Ontario, Canada
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Kingston, Ontario, Canada
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Toronto, Ontario, Canada
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Québec, Quebec, Canada
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Beijing, China
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Chengdu, China
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Chongqing, China
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Fuzhou, China
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Guangzhou, China
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Hangzhou, China
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Nanjing, China
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Shanghai, China
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Suzhou, China
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Wuhan, China
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Wuxi, China
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Xi'an, China
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Hradec Králove, Czechia
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Liberec, Czechia
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Nový Jicin, Czechia
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Olomouc, Czechia
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Opava, Czechia
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Pardubice, Czechia
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Prague, Czechia
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Zlín, Czechia
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Clermont-Ferrand, France
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Montpellier, France
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Nancy, France
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Paris, France
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Pierre-Bénite, France
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Strasbourg, France
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Suresnes, France
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Bonn, Germany
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Braunschweig, Germany
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Eisleben Lutherstadt, Germany
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Hamburg, Germany
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Hanover, Germany
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Leipzig, Germany
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Lübeck, Germany
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Nürtingen, Germany
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Sindelfingen, Germany
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Straubing, Germany
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Budapest, Hungary
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Győr, Hungary
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Pécs, Hungary
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Sopron, Hungary
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Beersheba, Israel
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Haifa, Israel
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Holon, Israel
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Kfar Saba, Israel
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Petah Tikva, Israel
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Ramat Gan, Israel
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Zrifin, Israel
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Chūōku, Japan
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Hakata-Ku, Japan
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Koshigaya, Japan
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Matsuyama, Japan
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Minamiku, Japan
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Miyazaki, Japan
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Nagano, Japan
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Nagasaki, Japan
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Osaka, Japan
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Osaka Sayama Shi, Japan
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Sakura, Japan
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Sapporo, Japan
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Yokohama, Japan
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Yufu, Japan
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Durango, Mexico
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Guadalajara, Mexico
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León, Mexico
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Mexico City, Mexico
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México, Mexico
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Morelia, Mexico
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Zapopan, Mexico
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Bialystok, Poland
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Bydgoszcz, Poland
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Krakow, Poland
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Kutno, Poland
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Lodz, Poland
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Lublin, Poland
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Siedlce, Poland
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Sochaczew, Poland
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Warsaw, Poland
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Wroclaw, Poland
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Bucharest, Romania
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Cluj-Napoca, Romania
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Craiova, Romania
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Târgu Mureş, Romania
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Barnaul, Russia
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Ivanovo, Russia
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Moscow, Russia
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Nizhny Novgorod, Russia
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Obninsk, Russia
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Omsk, Russia
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Pyatigorsk, Russia
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Rostov-on-Don, Russia
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Saint Petersburg, Russia
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Saransk, Russia
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Sochi, Russia
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Tambov, Russia
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Tomsk, Russia
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Tyumen, Russia
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Ufa, Russia
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Vologda, Russia
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Daegu, South Korea
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Daejeon, South Korea
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Goyang-si, South Korea
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Jeollanam-do, South Korea
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Seongnam-si, South Korea
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Seoul, South Korea
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Barcelona, Spain
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Córdoba, Spain
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Jerez de la Frontera, Spain
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Madrid, Spain
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Pamplona, Spain
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Gothenburg, Sweden
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Malmo, Sweden
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Örebro, Sweden
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Stockholm, Sweden
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Umeå, Sweden
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Uppsala, Sweden
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Vaxjo, Sweden
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Ankara, Turkey (Türkiye)
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Edirne, Turkey (Türkiye)
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Istanbul, Turkey (Türkiye)
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Izmir, Turkey (Türkiye)
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Mersin, Turkey (Türkiye)
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Cherkasy, Ukraine
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Dnipo, Ukraine
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Dnipro, Ukraine
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Ivano-Frankivsk, Ukraine
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Khakhiv, Ukraine
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Kharkiv, Ukraine
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Khmelnytsky, Ukraine
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Kyiv, Ukraine
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Lviv, Ukraine
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Odesa, Ukraine
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Poltava, Ukraine
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Uzhhorod, Ukraine
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Vinnitsa, Ukraine
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Zaporizhzhya, Ukraine
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Carlisle, United Kingdom
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Dundee, United Kingdom
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Glasgow, United Kingdom
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London, United Kingdom
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Newcastle upon Tyne, United Kingdom
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Oxford, United Kingdom
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Plymouth, United Kingdom
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Scunthorpe, United Kingdom
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Stockton-on-Tees, United Kingdom
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Wolverhampton, United Kingdom
Related Publications (10)
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.
PMID: 39163505DERIVEDRoy S, Sun Y, Chi KN, Ong M, Malone S, Wallis CJD, Kishan AU, Malone J, Swami U, Gebrael G, Brown JR, Jia AY, Morgan SC, Saad F, Chowdhury S, Agarwal N, Spratt DE. Early Prostate-Specific Antigen Response by 6 Months Is Predictive of Treatment Effect in Metastatic Hormone Sensitive Prostate Cancer: An Exploratory Analysis of the TITAN Trial. J Urol. 2024 Nov;212(5):672-681. doi: 10.1097/JU.0000000000004158. Epub 2024 Jul 26.
PMID: 39058790DERIVEDMerseburger AS, Agarwal N, Bjartell A, Uemura H, Soto AJ, Bhaumik A, Bohm J, Tran N, Krochmann N, Nematian-Samani M, Mundle SD, Brookman-May SD, Lopez-Gitlitz A, McCarthy SA, Chi K, Chowdhury S. Targeted Investigational Treatment Analysis of Novel Anti-androgen (TITAN) study: ultralow prostate-specific antigen decline with apalutamide plus androgen-deprivation therapy. BJU Int. 2024 Dec;134(6):982-991. doi: 10.1111/bju.16449. Epub 2024 Jun 28.
PMID: 38940282DERIVEDShen 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.
PMID: 37951974DERIVEDMerseburger AS, Agarwal N, Bhaumik A, Lefresne F, Karsh LI, Pereira de Santana Gomes AJ, Soto AJ, Given RW, Brookman-May SD, Mundle SD, McCarthy SA, Uemura H, Chowdhury S, Chi KN, Bjartell A. Apalutamide plus androgen deprivation therapy in clinical subgroups of patients with metastatic castration-sensitive prostate cancer: A subgroup analysis of the randomised clinical TITAN study. Eur J Cancer. 2023 Nov;193:113290. doi: 10.1016/j.ejca.2023.113290. Epub 2023 Aug 11.
PMID: 37708629DERIVEDAgarwal N, McQuarrie K, Bjartell A, Chowdhury S, Pereira de Santana Gomes AJ, Chung BH, Ozguroglu M, Juarez Soto A, Merseburger AS, Uemura H, Ye D, Given R, Basch E, Miladinovic B, Lopez-Gitlitz A, Chi KN. Apalutamide plus Androgen Deprivation Therapy for Metastatic Castration-Sensitive Prostate Cancer: Analysis of Pain and Fatigue in the Phase 3 TITAN Study. J Urol. 2021 Oct;206(4):914-923. doi: 10.1097/JU.0000000000001841. Epub 2021 May 27.
PMID: 34039013DERIVEDChi KN, Chowdhury S, Bjartell A, Chung BH, Pereira de Santana Gomes AJ, Given R, Juarez A, Merseburger AS, Ozguroglu M, Uemura H, Ye D, Brookman-May S, Mundle SD, McCarthy SA, Larsen JS, Sun W, Bevans KB, Zhang K, Bandyopadhyay N, Agarwal N. Apalutamide in Patients With Metastatic Castration-Sensitive Prostate Cancer: Final Survival Analysis of the Randomized, Double-Blind, Phase III TITAN Study. J Clin Oncol. 2021 Jul 10;39(20):2294-2303. doi: 10.1200/JCO.20.03488. Epub 2021 Apr 29.
PMID: 33914595DERIVEDUemura 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.
PMID: 32878613DERIVEDAgarwal N, McQuarrie K, Bjartell A, Chowdhury S, Pereira de Santana Gomes AJ, Chung BH, Ozguroglu M, Juarez Soto A, Merseburger AS, Uemura H, Ye D, Given R, Cella D, Basch E, Miladinovic B, Dearden L, Deprince K, Naini V, Lopez-Gitlitz A, Chi KN; TITAN investigators. Health-related quality of life after apalutamide treatment in patients with metastatic castration-sensitive prostate cancer (TITAN): a randomised, placebo-controlled, phase 3 study. Lancet Oncol. 2019 Nov;20(11):1518-1530. doi: 10.1016/S1470-2045(19)30620-5. Epub 2019 Sep 29.
PMID: 31578173DERIVEDChi KN, Agarwal N, Bjartell A, Chung BH, Pereira de Santana Gomes AJ, Given R, Juarez Soto A, Merseburger AS, Ozguroglu M, Uemura H, Ye D, Deprince K, Naini V, Li J, Cheng S, Yu MK, Zhang K, Larsen JS, McCarthy S, Chowdhury S; TITAN Investigators. Apalutamide for Metastatic, Castration-Sensitive Prostate Cancer. N Engl J Med. 2019 Jul 4;381(1):13-24. doi: 10.1056/NEJMoa1903307. Epub 2019 May 31.
PMID: 31150574DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Executive Medical Director
- Organization
- Aragon Pharmaceuticals, Inc.
Study Officials
- STUDY DIRECTOR
Janssen Research & Development, LLC Clinical Trial
Janssen Research & Development, LLC
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 1, 2015
First Posted
July 3, 2015
Study Start
November 27, 2015
Primary Completion
September 7, 2020
Study Completion (Estimated)
December 31, 2027
Last Updated
April 13, 2026
Results First Posted
January 18, 2022
Record last verified: 2026-04