An Efficacy and Safety Study of JNJ-56021927 (Apalutamide) in High-risk Prostate Cancer Subjects Receiving Primary Radiation Therapy: ATLAS

March 26, 2024 updated by: Aragon Pharmaceuticals, Inc.

ATLAS: A Randomized, Double-blind, Placebo-controlled Phase 3 Study of JNJ-56021927 in Subjects With High-risk, Localized or Locally Advanced Prostate Cancer Receiving Treatment With Primary Radiation Therapy

The purpose of this study is to determine if apalutamide plus gonadotropin releasing hormone (GnRH) agonist in participants with high-risk, localized or locally advanced prostate cancer receiving primary radiation therapy results in an improvement of metastasis-free survival.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a randomized, double-blind, placebo-controlled, multicenter study of apalutamide plus GnRH agonist compared with GnRH agonist among participants with high-risk, localized or locally advanced prostate cancer receiving primary radiation therapy (RT). The study will include a Screening Phase, Treatment Phase, a Posttreatment Phase, and a Long-term Follow-up Phase. Participants will either receive either apalutamide (experimental) or bicalutamide 50 milligram (mg) capsule plus placebo as control group. Safety will be monitored throughout the study.

Study Type

Interventional

Enrollment (Actual)

1503

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
      • Buenos Aires, Argentina
      • C.a.b.a., Argentina
      • Caba, Argentina
      • Ciudad Autonoma de Buenos Aires, Argentina
      • Pergamino, Argentina
      • Rosario, Argentina
      • San Salvador De Jujuy, Argentina
  • Belgium
      • Aalst, Belgium
      • Bonheiden, Belgium
      • Brussel, Belgium
      • Haine-St-Paul, Belgium
      • Leuven, Belgium
      • Liège, Belgium
      • Namur, Belgium
      • Roeselare, Belgium
      • Sint-Niklaas, Belgium
      • Turnhout, Belgium
      • Wilrijk, Belgium
  • Brazil
      • Barretos, Brazil
      • Belo Horizonte, Brazil
      • Campinas, Brazil
      • Curitiba, Brazil
      • Florianopolis, Brazil
      • Goiania, Brazil
      • Ijui, Brazil
      • Natal, Brazil
      • Porto Alegre, Brazil
      • Ribeirao Preto, Brazil
      • Rio de Janeiro, Brazil
      • Salvador, Brazil
      • Santo André, Brazil
      • Sao Jose do Rio Preto, Brazil
      • Sao Paulo, Brazil
      • Sorocaba, Brazil
      • São Paulo, Brazil
  • Canada
      • Quebec, Canada
    • Alberta
      • Calgary, Alberta, Canada
    • British Columbia
      • Surrey, British Columbia, Canada
      • Vancouver, British Columbia, Canada
      • Victoria, British Columbia, Canada
    • Ontario
      • London, Ontario, Canada
      • Ottawa, Ontario, Canada
      • Toronto, Ontario, Canada
    • Quebec
      • Gatineau, Quebec, Canada
      • Laval, Quebec, Canada
      • Montreal, Quebec, Canada
      • Montréal, Quebec, Canada
      • Sherbrooke, Quebec, Canada
  • China
      • Beijing, China
      • ChengDu, China
      • ChongQing, China
      • GuangZhou, China
      • Hangzhou, China
      • NanJing, China
      • Nanchang, China
      • Ningbo, China
      • ShangHai, China
      • Wuhan, 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
      • Amiens, France
      • Angers Cedex 02, France
      • Avignon Cedex 9, France
      • Bayonne, France
      • Besancon, France
      • Bordeaux, France
      • Brest, France
      • Dijon, France
      • Hyères, France
      • La Tronche, France
      • Le Mans, France
      • Lille, France
      • Marseille cedex 05, France
      • Marseilli, France
      • Montpellier, France
      • Neuilly-sur-Seine, France
      • Paris, France
      • Ris Orangis, France
      • Saint Herblain, France
      • Saint-Brieuc, France
      • Saint-Mande, France
      • Saint-Priest-en-Jarez, France
      • Strasbourg, France
      • Toulouse, France
      • Tours, France
      • Vandoeuvre-les-Nancy, France
      • Villejuif Cedex, France
      • Évry-Courcouronnes, France
  • Germany
      • Braunschweig, Germany
      • Chemnitz, Germany
      • Dessau, Germany
      • Frankfurt, Germany
      • Gronau, Germany
      • Jena, Germany
      • Münster, Germany
      • Nürtingen, Germany
      • Ulm, Germany
      • Weiden, Germany
  • Israel
      • Beer Yaakov, Israel
      • Beer-Sheva, Israel
      • Haifa, Israel
      • Jerusalem, Israel
      • Kfar Saba, Israel
      • Petach-Tikva, Israel
      • Ramat-Gan, Israel
      • Tel-Aviv, Israel
  • Korea, Republic of
      • Daegu, Korea, Republic of
      • Gyeonggi-do, Korea, Republic of
      • Jeollanam-do, Korea, Republic of
      • Seoul, Korea, Republic of
  • Malaysia
      • Georgetown, Malaysia
      • Kuala Lumpur, Malaysia
      • Kuching, Malaysia
      • Putrajaya, Malaysia
  • Mexico
      • Culiacan, Mexico
      • Guadalajara, Mexico
      • Leon, Mexico
      • Mexico, Mexico
      • Morelia, Mexico
      • Zapopan, Mexico
  • Netherlands
      • Alkmaar, Netherlands
      • Amsterdam, Netherlands
      • Den Haag, Netherlands
      • Nijmegen, Netherlands
      • Rotterdam, Netherlands
  • Poland
      • Bialystok, Poland
      • Bydgoszcz, Poland
      • Gdynia, Poland
      • Gliwice, Poland
      • Kielce, Poland
      • Lodz, Poland
      • Olsztyn, Poland
      • Poznan, Poland
      • Walbrzych, Poland
  • Romania
      • Bucuresti, Romania
      • Cluj-Napoca, Romania
      • Floresti, Romania
      • Iasi, Romania
      • Otopeni, Romania
      • Ploiesti, Romania
      • Sibiu, Romania
      • Targu Mures, Romania
      • Timisoara, 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
      • Saint-Petersburg, Russian Federation
      • Saransk, Russian Federation
      • St Petersburg, Russian Federation
      • Tambov, Russian Federation
      • Tyumen, Russian Federation
      • Ufa, Russian Federation
      • Vologda, Russian Federation
  • Spain
      • Barakaldo, Spain
      • Barcelona, Spain
      • Castellon, Spain
      • Hospitalet de Llobregat, Spain
      • Las Palmas de Gran Canaria, Spain
      • Madrid, Spain
      • Málaga, Spain
      • Reus, Spain
      • Santiago de Compostela, Spain
      • Sevilla, Spain
  • Sweden
      • Stockholm, Sweden
      • Umeå, Sweden
      • Örebro, Sweden
  • Taiwan
      • Kaohsiung, Taiwan
      • Taichung, Taiwan
      • Tainan, Taiwan
      • Taipei, Taiwan
      • Taipei City, Taiwan
      • Taoyuan, Taiwan
  • Turkey
      • Adana, Turkey
      • Ankara, Turkey
      • Edirne, Turkey
      • Istanbul, Turkey
      • Izmir, Turkey
      • Kayseri, Turkey
      • Kocaeli, Turkey
  • Ukraine
      • Dnipro, Ukraine
      • Khakhiv, Ukraine
      • Kyiv, Ukraine
      • Lviv, Ukraine
  • United Kingdom
      • Aberdeen, United Kingdom
      • Birmingham, United Kingdom
      • Bristol, United Kingdom
      • Derby, United Kingdom
      • Glasgow, United Kingdom
      • Oxford, United Kingdom
      • Plymouth, United Kingdom
      • Preston, United Kingdom
      • Sheffield, United Kingdom
      • Sutton, United Kingdom
      • Wolverhampton, United Kingdom
  • United States
    • Alabama
      • Homewood, Alabama, United States
    • Arizona
      • Chandler, Arizona, United States
      • Scottsdale, Arizona, United States
      • Tucson, Arizona, United States
    • California
      • Bakersfield, California, United States
      • Los Angeles, California, United States
      • Orange, California, United States
      • San Bernardino, California, United States
      • San Diego, California, United States
      • San Francisco, California, United States
    • Colorado
      • Aurora, Colorado, United States
      • Denver, Colorado, United States
    • Connecticut
      • Middlebury, Connecticut, United States
    • Florida
      • Bradenton, Florida, United States
      • Daytona Beach, Florida, United States
      • Fort Myers, Florida, United States
      • Hialeah, Florida, United States
      • Lakewood Ranch, Florida, United States
      • Naples, Florida, United States
      • Plantation, Florida, United States
    • Idaho
      • Meridian, Idaho, United States
    • Illinois
      • Evergreen Park, Illinois, United States
      • Harvey, Illinois, United States
    • Indiana
      • Jeffersonville, Indiana, United States
    • Kansas
      • Wichita, Kansas, United States
    • Kentucky
      • Ashland, Kentucky, United States
    • Louisiana
      • New Orleans, Louisiana, United States
      • Shreveport, Louisiana, United States
    • Maine
      • Scarborough, Maine, United States
    • Maryland
      • Baltimore, Maryland, United States
    • Massachusetts
      • Boston, Massachusetts, United States
    • Missouri
      • Saint Louis, Missouri, United States
    • New Jersey
      • Morristown, New Jersey, United States
    • New York
      • Albany, New York, United States
      • Bronx, New York, United States
      • Brooklyn, New York, United States
      • New York, New York, United States
      • Poughkeepsie, New York, United States
      • Rochester, New York, United States
      • Syracuse, New York, United States
    • North Carolina
      • Cary, North Carolina, United States
      • Raleigh, North Carolina, United States
    • Oregon
      • Portland, Oregon, United States
      • Springfield, Oregon, United States
    • Pennsylvania
      • Bala-Cynwyd, Pennsylvania, United States
      • Bryn Mawr, Pennsylvania, United States
      • Lancaster, Pennsylvania, United States
      • Philadelphia, Pennsylvania, United States
    • Rhode Island
      • East Greenwich, Rhode Island, United States
    • South Carolina
      • Charleston, South Carolina, United States
      • Myrtle Beach, South Carolina, United States
    • Tennessee
      • Nashville, Tennessee, United States
    • Texas
      • Dallas, Texas, United States
      • Houston, Texas, United States
      • San Antonio, Texas, United States
    • Virginia
      • Fairfax, Virginia, United States
      • Virginia Beach, Virginia, United States
    • Washington
      • Burien, Washington, United States
      • Spokane, Washington, United States
    • West Virginia
      • Morgantown, West Virginia, 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:

  • Age >= 18 years
  • Indicated and planned to receive primary radiation therapy for prostate cancer
  • Histologically confirmed adenocarcinoma of an intact prostate, and 1 of the following at diagnosis: 1) Gleason score >=8 and >=cT2c, 2) Gleason score >=7, PSA >=20 nanogram per milliliters (ng/mL), and >=cT2c
  • Charlson index (CCI) <=3
  • An Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) grade of 0 or 1
  • Adequate organ function: (1) aspartate aminotransferase (AST), alanine aminotransferase (ALT), within normal limits (WNL), (2) serum creatinine less than (<) 1.5 milligram/deciliter (mg/dL) (<133 micromoles/Liter [mcmol/L]), (3) platelets greater than or equal to (>=)140,000/microLiter (mcL), independent of transfusion and/or growth factors within 3 months prior to randomization, (4) Hemoglobin >= 12.0 gram/deciliter (g/dL) (7.4 millimloes [mmol], independent of transfusion and/or growth factors within 3 months prior to randomization
  • Participants who are sexually active (even men with vasectomies) and willing to use a condom and agree not to donate sperm during the trial
  • Signed, written, informed consent
  • Be able to swallow whole study drug tablets

Exclusion Criteria: -

  • Presence of distant metastasis, (clinical stage M1). Isolated pelvic nodal disease below the iliac bifurcation (clinical stage N1) is not an exclusion. Diagnosis of distant metastasis (clinical M stage; M0 versus M1a, M1b, M1c) and pelvic nodal disease (clinical N stage; N1 versus N0) will be assessed by central radiological review. Patients are considered eligible only if the central radiological review confirms clinical stage M0.
  • Prior treatment with gonadotropin releasing hormone (GnRH) analogue or anti-androgen or both for >3 months prior to randomization
  • Bilateral orchiectomy
  • History of pelvic radiation
  • Prior systemic (example [e.g.], chemotherapy) or local (e.g. radical prostatectomy, cryotherapy) treatment for prostate cancer
  • History of seizure or any condition that may predispose to seizure (including, but not limited to prior stroke, transient ischemic attack or loss of consciousness <= 1 year prior to randomization; brain arteriovenous malformation; or intracranial masses such as schwannomas and meningiomas that are causing edema or mass effect)
  • Prior treatment with enzalutamide, abiraterone acetate, orteronel, galeterone, ketoconazole, aminoglutethimide, estrogens, megestrol acetate, and progestational agents (including cyproterone acetate) for prostate cancer
  • Prior treatment with radiopharmaceutical agents (e.g., strontium-89) or immunotherapy (e.g., sipuleucel-T) for prostate cancer
  • Prior treatment with systemic glucocorticoids ≤4 weeks prior to randomization or is expected to require long-term use of corticosteroids during the study
  • Use of 5-alpha reductase inhibitors (e.g., dutasteride, finasteride) <=4 weeks prior to randomization
  • Use of any investigational agent <=4 weeks prior to randomization
  • Current chronic use of opioid analgesics for >=3 weeks for oral or >7 days for non-oral formulations
  • Major surgery <=4 weeks prior to randomization
  • Current or prior treatment with anti-epileptic medications for the treatment of seizures
  • Gastrointestinal conditions affecting absorption
  • Known or suspected contraindications or hypersensitivity to apalutamide, bicalutamide or GnRH agonists or any of the components of the formulations
  • Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject

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: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Apalutamide
Participants will receive apalutamide (240 mg), by mouth, once daily for overall 30 months, plus bicalutamide placebo, by mouth, once daily, for four months from randomization. All participants are treated with gonadotropin releasing hormone (GnRH) agonist for 30 months from randomization and radiation therapy to the prostate started at about 8 weeks after randomization.
Drug: Apalutamide
Drug: Bicalutamide Placebo
Drug: GnRH (agonist)
Radiation: 74-80 Grays (units of radiation)
Active Comparator: Control group
Participants will receive apalutamide placebo, by mouth, once daily for overall 30 months, plus bicalutamide (50 mg), by mouth, once daily, for four months from randomization. All participants are treated with gonadotropin releasing hormone (GnRH) agonist for 30 months from randomization and radiation therapy to the prostate started at about 8 weeks after randomization.
Drug: Bicalutamide
Drug: GnRH (agonist)
Radiation: 74-80 Grays (units of radiation)
Drug: Apalutamide Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Metastasis-free survival
Time Frame: 108 Months
Metastasis-free survival is defined as the time from randomization to the date of the first occurrence of radiographic bone or soft tissue distant metastasis based on conventional imaging by blinded independent central review (BICR), histopathologic diagnosis of distant metastasis, or death from any cause, whichever occurs first.
108 Months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Event-free Survival
Time Frame: 108 Months
Event-free survival is defined as the time from randomization to the date of the first occurrence of prostate specific antigen (PSA) failure by the Phoenix definition, local or regional disease recurrence on conventional imaging by BICR or histopathologic diagnosis, distant metastasis on conventional imaging by BICR or histopathologic diagnosis, or death.
108 Months
Time to Prostate Specific Antigen (PSA) Progression
Time Frame: 108 Months
Time to PSA progression is defined as time from randomization to the date of PSA nadir plus (+) 0.5 nanograms per milliliter (ng/mL) and rising.
108 Months
Overall Survival (OS)
Time Frame: 108 Months
OS is defined as the time from randomization to date of death from any cause.
108 Months
Time to Distant Metastasis
Time Frame: 108 Months
Time to distant metastasis is defined as the time from randomization to the date of the first occurrence of radiographic or pathological bone or soft tissue distant metastasis on conventional imaging by BICR or histopathologic diagnosis of distant metastasis.
108 Months
Time to Next Local or Systemic Treatment
Time Frame: 108 Months
Time to next local or systemic treatment defined as time from randomization to first subsequent therapy, including re-initiation of androgen deprivation therapy (ADT) and local treatments for local-regional recurrence or distant metastasis.
108 Months
MFS by Conventional or Positron Emission Tomography (PET) Imaging
Time Frame: 108 Months
MFS by conventional or PET imaging is defined as time from randomization to the date of the first occurrence of radiographic bone or soft tissue distant metastasis based on conventional imaging or PET imaging, histopathologic diagnosis of distant metastasis, or death from any cause, whichever occurs first.
108 Months

Collaborators and Investigators

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

Sponsor

Aragon Pharmaceuticals, Inc.

Investigators

  • Study Director: Aragon Pharmaceuticals, Inc. Clinical Trial, Aragon Pharmaceuticals, Inc.

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 19, 2015

Primary Completion (Estimated)

June 28, 2024

Study Completion (Estimated)

December 29, 2028

Study Registration Dates

First Submitted

August 21, 2015

First Submitted That Met QC Criteria

August 21, 2015

First Posted (Estimated)

August 24, 2015

Study Record Updates

Last Update Posted (Actual)

March 27, 2024

Last Update Submitted That Met QC Criteria

March 26, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CR106935
  • 56021927PCR3003 (Other Identifier: Aragon Pharmaceuticals, Inc.)
  • 2015-003007-38 (EudraCT Number)

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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