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

April 23, 2024 updated by: Aragon Pharmaceuticals, Inc.

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)

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

1052

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
      • 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
  • Australia
      • Albury, Australia
      • Elizabeth Vale, Australia
      • Kogarah, Australia
      • Port Macquarie, Australia
      • South Brisbane, Australia
      • St Leonards, Australia
  • Brazil
      • Barretos, Brazil
      • Florianopolis, Brazil
      • Goiania, 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
      • Quebec, Canada
    • Alberta
      • Calgary, Alberta, Canada
    • British Columbia
      • Vancouver, British Columbia, Canada
    • Ontario
      • Hamilton, Ontario, Canada
      • Kingston, Ontario, Canada
      • Toronto, Ontario, Canada
  • China
      • 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
  • Czechia
      • 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
  • France
      • Clermont Ferrand, France
      • Montpellier, France
      • Nancy, France
      • Paris, France
      • Pierre Bénite, France
      • Strasbourg, France
      • Suresnes, France
  • Germany
      • Bonn, Germany
      • Braunschweig, Germany
      • Hamburg, Germany
      • Hannover, Germany
      • Leipzig, Germany
      • Lubeck, Germany
      • Lutherstadt Eisleben, Germany
      • Nürtingen, Germany
      • Sindelfingen, Germany
      • Straubing, Germany
  • Hungary
      • Budapest, Hungary
      • Győr, Hungary
      • Pécs, Hungary
      • Sopron, Hungary
  • Israel
      • Beer Sheva, Israel
      • Haifa, Israel
      • Holon, Israel
      • Kfar Saba, Israel
      • Petach Tikva, Israel
      • Ramat Gan, Israel
      • Zrifin, Israel
  • Japan
      • Chuo-ku, Chiba-City,, Japan
      • Hakata-Ku, Japan
      • Koshigaya, Japan
      • Matsuyama, Japan
      • Minami-Ku, Sagamihara-Shi, Japan
      • Miyazaki, Japan
      • Nagano-shi, Japan
      • Nagasaki-shi, Japan
      • Osaka, Japan
      • Osaka Sayama shi, 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
  • Mexico
      • Ciudad de México, Mexico
      • Durango, Mexico
      • Guadalajara, Mexico
      • Leon, Mexico
      • Mexico, Mexico
      • Mexico City, Mexico
      • Morelia, Mexico
      • Zapopan, Mexico
  • Poland
      • Bialystok, Poland
      • Bydgoszcz, Poland
      • Krakow, Poland
      • Kutno, Poland
      • Lodz, Poland
      • Lublin, Poland
      • Siedlce, Poland
      • Sochaczew, Poland
      • Warszawa, Poland
      • Wroclaw, Poland
  • Romania
      • 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
  • Spain
      • Barcelona, Spain
      • Cordoba, Spain
      • Jerez de la Frontera, Spain
      • Madrid, Spain
      • Pamplona, Spain
  • Sweden
      • Göteborg, Sweden
      • Malmö, Sweden
      • Stockholm, Sweden
      • Umeå, Sweden
      • Uppsala, Sweden
      • Växjö, Sweden
      • Örebro, Sweden
  • Turkey
      • Ankara, Turkey
      • Edirne, Turkey
      • Istanbul, Turkey
      • Izmir, Turkey
      • Mersin, Turkey
  • Ukraine
      • 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
  • United States
    • Alabama
      • Homewood, Alabama, United States
    • Arizona
      • Tucson, Arizona, United States
    • California
      • San Bernardino, California, United States
      • San Diego, California, United States
    • Colorado
      • Denver, Colorado, United States
    • Connecticut
      • Norwalk, Connecticut, United States
    • Florida
      • Fort Myers, Florida, United States
    • Illinois
      • Chicago, Illinois, United States
    • Indiana
      • Fort Wayne, Indiana, United States
      • Jeffersonville, Indiana, United States
    • Louisiana
      • New Orleans, Louisiana, United States
    • Maryland
      • Baltimore, Maryland, United States
      • Rockville, Maryland, United States
    • Michigan
      • Lansing, Michigan, United States
      • Troy, Michigan, United States
    • Nebraska
      • Omaha, Nebraska, United States
    • Nevada
      • Las Vegas, Nevada, United States
    • New York
      • Bronx, New York, United States
      • Brooklyn, New York, United States
      • Poughkeepsie, New York, United States
      • Syracuse, New York, United States
    • North Carolina
      • Raleigh, North Carolina, United States
      • Salisbury, North Carolina, United States
    • Ohio
      • Cleveland, Ohio, United States
      • Middleburg Heights, Ohio, United States
    • Oregon
      • Springfield, Oregon, United States
    • Pennsylvania
      • Bala-Cynwyd, Pennsylvania, United States
      • Bryn Mawr, Pennsylvania, United States
      • Lancaster, Pennsylvania, United States
    • South Carolina
      • Charleston, South Carolina, United States
    • Tennessee
      • Nashville, Tennessee, United States
    • Texas
      • Dallas, Texas, United States
      • Houston, Texas, United States
      • San Antonio, Texas, United States
    • Utah
      • Salt Lake City, Utah, United States
    • Virginia
      • Richmond, Virginia, United States
      • Virginia Beach, Virginia, United States
    • Washington
      • Burien, Washington, United States
      • Spokane, Washington, United States
    • Wisconsin
      • Milwaukee, Wisconsin, United States

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / 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:
  • ARN-509
  • JNJ-56021927
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: 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.
Drug: Placebo
Participants will receive Placebo orally once daily in each 28 day treatment cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Radiographic Progression-free Survival (rPFS)
Time Frame: Up to 35 months
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)
Time Frame: Up to 57 months
OS was defined as the time from date of randomization to date of death from any cause.
Up to 57 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to Initiation of Cytotoxic Chemotherapy
Time Frame: Up to 57 months
Time to initiation of cytotoxic chemotherapy was defined as the time from date of randomization to the date of initiation of cytotoxic chemotherapy for prostate cancer.
Up to 57 months
Time to Pain Progression
Time Frame: Up to 57 months
Time to pain progression was defined as the time from the date of randomization to the date of the first observation of pain progression. Pain progression was defined as an average increase by 2 points from baseline to greater than (>) 4 on the Brief Pain Inventory - Short Form (BPI-SF) worst pain intensity (item 3) with no decrease in opioids confirmed greater than equal to (>=) 3 weeks apart or initiation of chronic opioids, whichever occurred first. BPI-SF is a self-administered questionnaire developed to assess severity of pain and impact of pain on daily functions. Item 3 (worst pain intensity) asks participants to rate worst pain in prior 7-days on a 0-10 numeric rating scale, where "0" indicates "No pain" and "10" indicates "Pain as bad as you can imagine." A lower score is better.
Up to 57 months
Time to Chronic Opioid Use
Time Frame: Up to 57 months
Time to chronic opioid use was defined as the time from date of randomization to the first date of confirmed chronic opioid use. For participants entering the study without receiving opioids, chronic opioid use was defined as administration of opioid analgesics lasting for greater than or equal to (>=) 3 weeks for oral or >=7 days for non-oral formulations. For participants entering the study already receiving opioids, chronic opioid use was defined as a >=30 percent (%) increase in total daily dose of the opioid analgesics lasting for >= 3 weeks for oral or >= 7 days for non-oral formulation.
Up to 57 months
Time to Skeletal-related Event (SRE)
Time Frame: Up to 57 months
Time to SRE was defined as the time from the date of randomization to the date of the first observation of an SRE. A SRE was defined as the occurrence of either a pathological fracture, or spinal cord compression, or radiation to bone, or surgery to bone.
Up to 57 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Aragon Pharmaceuticals, Inc.

Investigators

  • Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 27, 2015

Primary Completion (Actual)

September 7, 2020

Study Completion (Estimated)

September 5, 2024

Study Registration Dates

First Submitted

July 1, 2015

First Submitted That Met QC Criteria

July 1, 2015

First Posted (Estimated)

July 3, 2015

Study Record Updates

Last Update Posted (Estimated)

April 25, 2024

Last Update Submitted That Met QC Criteria

April 23, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CR107614
  • 2015-000735-32 (EudraCT Number)
  • 56021927PCR3002 (Other Identifier: Janssen Research & Development, LLC)

Drug and device information, study documents

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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