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A Study of Apalutamide (JNJ-56021927, ARN-509) Plus Androgen Deprivation Therapy (ADT) Versus ADT in Participants With mHSPC (TITAN)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02489318
Recruitment Status : Active, not recruiting
First Posted : July 3, 2015
Last Update Posted : July 23, 2021
Information provided by (Responsible Party):
Aragon Pharmaceuticals, Inc.

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.

Condition or disease Intervention/treatment Phase
Prostate Cancer Drug: Apalutamide Drug: Placebo Drug: Androgen Deprivation Therapy (ADT) Phase 3

Detailed Description:
This is a randomized (study medication assigned to participants by chance), double-blind (neither the researchers nor the participants know what treatment the participant is receiving), placebo-controlled, multinational, multicenter study of apalutamide in participants with mHSPC. The study consists of 4 Phases: Screening Phase (up to 28 days before randomization), Treatment Phase (28 day treatment cycles until disease progression or the occurrence of unacceptable treatment related toxicity), an End of Treatment Phase (until 30 days after the last dose of study drug), and then a Survival Follow up Phase. In the event of a positive study result and notification of unblinding at either of the interim analyses or at the final analysis, participants in the treatment Phase will have the opportunity to enroll in an Open-label Extension Phase, which will allow participants to receive active drug (apalutamide) for approximately 3 years. Participants who are receiving apalutamide in the Open-label Extension Phase may continue receiving apalutamide in the Long-term Extension (LTE) Phase if they will continue to derive benefit from treatment (based on investigator assessment). Participants' safety will be monitored throughout the study.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1052 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: 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)
Actual Study Start Date : November 27, 2015
Actual Primary Completion Date : September 7, 2020
Estimated Study Completion Date : March 1, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer
Drug Information available for: Apalutamide

Arm Intervention/treatment
Experimental: Apalutamide plus ADT
Participants will receive apalutamide 240 milligram (mg) (4X 60 mg tablets) with ADT.
Drug: Apalutamide
Participants will receive apalutamide 240 mg (4 x 60 mg) tablets orally once daily in each 28 day treatment cycles.
Other Names:
  • JNJ-56021927
  • ARN-509

Drug: Androgen Deprivation Therapy (ADT)
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.

Experimental: Placebo plus ADT
Participants will receive matching Placebo with ADT.
Drug: Placebo
Participants will receive Placebo orally once daily in each 28 day treatment cycles.

Drug: Androgen Deprivation Therapy (ADT)
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.

Primary Outcome Measures :
  1. Radiographic Progression-Free Survival (rPFS) [ Time Frame: Up to 54 Months ]
    The rPFS is 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 occurs first.

  2. Overall Survival (OS) [ Time Frame: Up to 54 Months ]
    The OS is defined as the time from date of randomization to date of death from any cause.

Secondary Outcome Measures :
  1. Time to Pain Progression [ Time Frame: Up to 54 Months ]
    Time to pain progression is defined as the time from the date of randomization to the date of the first observation of pain progression.

  2. Time to Skeletal-Related Event (SRE) [ Time Frame: Up to 54 Months ]
    Time to SRE is defined as the time from the date of randomization to the date of the first occurrence of a fracture or treatment for the fracture. The SRE is defined as the occurrence of symptomatic pathological fracture, spinal cord compression, radiation to new bone lesions, or surgery to bone.

  3. Time to Chronic Opioid Use [ Time Frame: Up to 54 Months ]
    Time to chronic opioid use is defined as the time from date of randomization to the first date of opioid use or first date of an increase in the total daily dose.

  4. Time to Initiation of Cytotoxic Chemotherapy [ Time Frame: Up to 54 Months ]
    Time to initiation of cytotoxic chemotherapy is defined as the time from date of randomization to the date of initiation of cytotoxic chemotherapy.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02489318

Hide Hide 229 study locations
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United States, Alabama
Homewood, Alabama, United States
United States, Arizona
Tucson, Arizona, United States
United States, California
San Bernardino, California, United States
San Diego, California, United States
United States, Colorado
Denver, Colorado, United States
United States, Connecticut
Norwalk, Connecticut, United States
United States, Florida
Fort Myers, Florida, United States
United States, Illinois
Chicago, Illinois, United States
United States, Indiana
Fort Wayne, Indiana, United States
Jeffersonville, Indiana, United States
United States, Louisiana
New Orleans, Louisiana, United States
United States, Maryland
Baltimore, Maryland, United States
Rockville, Maryland, United States
United States, Michigan
Lansing, Michigan, United States
Troy, Michigan, United States
United States, Nebraska
Omaha, Nebraska, United States
United States, Nevada
Las Vegas, Nevada, United States
United States, New York
Bronx, New York, United States
Brooklyn, New York, United States
Poughkeepsie, New York, United States
Syracuse, New York, United States
United States, North Carolina
Raleigh, North Carolina, United States
Salisbury, North Carolina, United States
United States, Ohio
Cleveland, Ohio, United States
Middleburg Heights, Ohio, United States
United States, Oregon
Springfield, Oregon, United States
United States, Pennsylvania
Bala-Cynwyd, Pennsylvania, United States
Bryn Mawr, Pennsylvania, United States
Lancaster, Pennsylvania, United States
United States, South Carolina
Charleston, South Carolina, United States
United States, Tennessee
Nashville, Tennessee, United States
United States, Texas
Dallas, Texas, United States
Houston, Texas, United States
San Antonio, Texas, United States
United States, Utah
Salt Lake City, Utah, United States
United States, Virginia
Richmond, Virginia, United States
Virginia Beach, Virginia, United States
United States, Washington
Burien, Washington, United States
Spokane, Washington, United States
United States, Wisconsin
Milwaukee, Wisconsin, United States
Berazategui, Argentina
C.a.b.a., Argentina
Capital Federal, Argentina
Ciudad Automoma Buenos Aires, Argentina
Ciudad Autonoma de Buenos Aires, Argentina
Ciudad De Buenos Aires, Argentina
Cordoba, Argentina
La Plata, Argentina
Pergamino, Argentina
Rosario, Argentina
San Miguel de Tucuman, Argentina
San Salvador de Jujuy, Argentina
Albury, Australia
Elizabeth Vale, Australia
Kogarah, Australia
Port Macquarie, Australia
South Brisbane, Australia
St Leonards, Australia
Barretos, Brazil
Florianópolis, Brazil
Goiânia, Brazil
Ijui, Brazil
Natal, Brazil
Ribeirao Preto, Brazil
Rio de Janeiro, Brazil
Salvador, Brazil
Santo André, Brazil
Sao Paulo, Brazil
Sorocaba, Brazil
São Paulo, Brazil
Canada, Alberta
Calgary, Alberta, Canada
Canada, British Columbia
Vancouver, British Columbia, Canada
Canada, Ontario
Hamilton, Ontario, Canada
Kingston, Ontario, Canada
Toronto, Ontario, Canada
Quebec, Canada
Beijing, China
ChengDu, China
ChongQing, China
Fuzhou, China
Guangzhou, China
Hangzhou, China
NanJing, China
ShangHai, China
Suzhou, China
WuHan, China
Wuxi, China
Xi'An, China
Hradec Králove, Czechia
Liberec, Czechia
Nový Jicin, Czechia
Olomouc, Czechia
Opava, Czechia
Pardubice, Czechia
Praha 10, Czechia
Praha 2, Czechia
Praha 4, Czechia
Praha 5, Czechia
Praha 8, Czechia
Zlin, Czechia
Clermont Ferrand, France
Montpellier, France
Nancy, France
Paris, France
Pierre Bénite, France
Strasbourg, France
Suresnes, France
Bonn, Germany
Braunschweig, Germany
Hamburg, Germany
Hannover, Germany
Leipzig, Germany
Lubeck, Germany
Lutherstadt Eisleben, Germany
Nürtingen, Germany
Sindelfingen, Germany
Straubing, Germany
Budapest, Hungary
Győr, Hungary
Pécs, Hungary
Sopron, Hungary
Beer Sheva, Israel
Haifa, Israel
Holon, Israel
Kfar Saba, Israel
Petach Tikva, Israel
Ramat Gan, Israel
Zrifin, Israel
Chuo-ku, Chiba-City,, Japan
Hakata-Ku, Japan
Koshigaya, Japan
Matsuyama, Japan
Minami-Ku, Sagamihara-Shi, Japan
Miyazaki, Japan
Nagano, Japan
Nagasaki, Japan
Osaka-Sayama, Japan
Osaka, Japan
Sakura, Japan
Sapporo, Japan
Yokohama, Japan
Yufu, Japan
Korea, Republic of
Daegu, Korea, Republic of
Daejeon, Korea, Republic of
Goyang-Si, Korea, Republic of
Jeollanam-do, Korea, Republic of
Seongnam-si, Korea, Republic of
Seoul, Korea, Republic of
Ciudad de México, Mexico
Durango, Mexico
Guadalajara, Mexico
Leon, Mexico
Mexico City, Mexico
Mexico, Mexico
Morelia, Mexico
Zapopan, Mexico
Bialystok, Poland
Bydgoszcz, Poland
Krakow, Poland
Kutno, Poland
Lodz, Poland
Lublin, Poland
Siedlce, Poland
Sochaczew, Poland
Warszawa, Poland
Wroclaw, Poland
Bucharest, Romania
Cluj Napoca, Romania
Craiova, Romania
Targu Mures, Romania
Russian Federation
Barnaul, Russian Federation
Ivanovo, Russian Federation
Moscow, Russian Federation
Nizhny Novgorod, Russian Federation
Obninsk, Russian Federation
Omsk, Russian Federation
Pyatigorsk, Russian Federation
Rostov-on-Don, Russian Federation
Ryazan, Russian Federation
Saint-Petersburg, Russian Federation
Saransk, Russian Federation
Sochi, Russian Federation
St Petersburg, Russian Federation
Tambov, Russian Federation
Tomsk, Russian Federation
Tyumen, Russian Federation
Ufa, Russian Federation
Vologda, Russian Federation
Barcelona, Spain
Cordoba, Spain
Jerez de la Frontera, Spain
Madrid, Spain
Pamplona, Spain
Göteborg, Sweden
Malmö, Sweden
Stockholm, Sweden
Umeå, Sweden
Uppsala, Sweden
Växjö, Sweden
Örebro, Sweden
Ankara, Turkey
Edirne, Turkey
Istanbul, Turkey
Izmir, Turkey
Mersin, Turkey
Cherkasy, Ukraine
Dnipo, Ukraine
Dnipro, Ukraine
Ivano-Frankivsk, Ukraine
Khakhiv, Ukraine
Kharkiv, Ukraine
Khmelnytsky, Ukraine
Kyiv, Ukraine
Lviv, Ukraine
Odesa, Ukraine
Poltava, Ukraine
Uzhgorod, Ukraine
Vinnitsa, Ukraine
Zaporizhzhya, Ukraine
United Kingdom
Carlisle, United Kingdom
Dundee, United Kingdom
Glasgow, United Kingdom
London, United Kingdom
Newcastle Upon Tyne, United Kingdom
Oxford, United Kingdom
Plymouth, United Kingdom
Scunthorpe, United Kingdom
Stockton on Tees, United Kingdom
Wolverhampton, United Kingdom
Sponsors and Collaborators
Aragon Pharmaceuticals, Inc.
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Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
Publications automatically indexed to this study by Identifier (NCT Number):

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Responsible Party: Aragon Pharmaceuticals, Inc. Identifier: NCT02489318    
Other Study ID Numbers: CR107614
2015-000735-32 ( EudraCT Number )
56021927PCR3002 ( Other Identifier: Janssen Research & Development, LLC )
First Posted: July 3, 2015    Key Record Dates
Last Update Posted: July 23, 2021
Last Verified: July 2021

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Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Aragon Pharmaceuticals, Inc.:
Prostate Cancer
Androgen Deprivation Therapy
Metastatic Hormone-sensitive Prostate Cancer
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Prostatic Diseases
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs