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

NCT ID: NCT02489318

Last Updated: 2025-11-13

Study Results

Results available

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Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

1052 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-11-27

Study Completion Date

2027-12-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Prostate Cancer

Keywords

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Prostate Cancer JNJ-56021927 Androgen Deprivation Therapy ARN-509 Apalutamide TITAN Metastatic Hormone-sensitive Prostate Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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Apalutamide plus ADT

Participants will receive apalutamide 240 milligram (mg) (4X 60 mg tablets) with ADT.

Group Type EXPERIMENTAL

Apalutamide

Intervention Type DRUG

Participants will receive apalutamide 240 mg (4 x 60 mg) tablets orally once daily in each 28 day treatment cycles.

Androgen Deprivation Therapy (ADT)

Intervention Type DRUG

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.

Placebo plus ADT

Participants will receive matching Placebo with ADT.

Group Type EXPERIMENTAL

Placebo

Intervention Type DRUG

Participants will receive Placebo orally once daily in each 28 day treatment cycles.

Androgen Deprivation Therapy (ADT)

Intervention Type DRUG

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.

Interventions

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Apalutamide

Participants will receive apalutamide 240 mg (4 x 60 mg) tablets orally once daily in each 28 day treatment cycles.

Intervention Type DRUG

Placebo

Participants will receive Placebo orally once daily in each 28 day treatment cycles.

Intervention Type 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.

Intervention Type DRUG

Other Intervention Names

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JNJ-56021927 ARN-509

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Aragon Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

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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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Salt Lake City, Utah, 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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Ryazan, , 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

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Countries

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United States Argentina Australia Brazil Canada China Czechia France Germany Hungary Israel Japan Mexico Poland Romania Russia South Korea Spain Sweden Turkey (Türkiye) Ukraine United Kingdom

References

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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.

Reference Type DERIVED
PMID: 39163505 (View on PubMed)

Merseburger 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.

Reference Type DERIVED
PMID: 38940282 (View on PubMed)

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.

Reference Type DERIVED
PMID: 37951974 (View on PubMed)

Merseburger 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.

Reference Type DERIVED
PMID: 37708629 (View on PubMed)

Agarwal 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.

Reference Type DERIVED
PMID: 34039013 (View on PubMed)

Chi 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.

Reference Type DERIVED
PMID: 33914595 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32878613 (View on PubMed)

Agarwal 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.

Reference Type DERIVED
PMID: 31578173 (View on PubMed)

Chi 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.

Reference Type DERIVED
PMID: 31150574 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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56021927PCR3002

Identifier Type: OTHER

Identifier Source: secondary_id

2015-000735-32

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR107614

Identifier Type: -

Identifier Source: org_study_id