Clinical trial NCT02531516: An Efficacy and Safety Study of JNJ-56021927 (Apalutamide) in High-risk Prostate Cancer Subjects Receiving Primary Radiation Therapy: ATLAS
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Prostatic Neoplasms
Keywords: Prostatic neoplasms
Prostate Cancer
High-Risk prostate cancer
JNJ-56021927
Apalutamide
ATLAS
Radiation
Long-term hormone therapy
Localized or locally advanced prostate cancer
Janssen
Lead sponsor: Aragon Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2015-08-24
Enrollment: 1503
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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 (RT) results in an improvement of metastasis-free survival based on conventional or prostate specific membrane antigen-positron emission tomography (PSMA-PET) imaging evaluated by blinded independent central review (BICR).

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.

Eligibility criteria: 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

Primary outcomes:
measure: Metastasis-free Survival
timeFrame: 108 Months
Secondary outcomes:
measure: Event-free Survival on Conventional Imaging or PSMA-PET Imaging
timeFrame: 108 Months
measure: Time to Prostate Specific Antigen (PSA) Progression
timeFrame: 108 Months
measure: Metastasis-free Survival (MFS) on Conventional Imaging by Blinded Independent Central Review (BICR)
timeFrame: 108 Months
measure: No Evidence of Disease (NED)
timeFrame: 108 Months
measure: Overall Survival (OS)
timeFrame: 108 Months
measure: Time to Distant Metastasis
timeFrame: 108 Months
measure: Event-free Survival on Conventional Imaging
timeFrame: 108 Months
measure: Time to Next Local or Systemic Treatment
timeFrame: 108 Months
Other outcomes:
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city: Bonheiden
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city: Brussel
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city: Haine-St-Paul
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city: Leuven
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city: Liège
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city: Namur
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city: Roeselare
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city: Sint-Niklaas
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city: Beijing
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city: Olomouc
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city: Praha 10
country: Czechia
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country: Czechia
city: Zlin
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city: Amiens
country: France
city: Angers Cedex 02
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city: Avignon Cedex 9
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country: France
city: Besancon
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city: Bordeaux
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city: Marseille cedex 05
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country: Romania
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country: Romania
city: Barnaul
country: Russian Federation
city: Ivanovo
country: Russian Federation
city: Moscow
country: Russian Federation
city: Nizhny Novgorod
country: Russian Federation
city: Obninsk
country: Russian Federation
city: Omsk
country: Russian Federation
city: Pyatigorsk
country: Russian Federation
city: Rostov-on-Don
country: Russian Federation
city: Ryazan
country: Russian Federation
city: Saint Petersburg
country: Russian Federation
city: Saint-Petersburg
country: Russian Federation
city: Saransk
country: Russian Federation
city: St Petersburg
country: Russian Federation
city: Tambov
country: Russian Federation
city: Tyumen
country: Russian Federation
city: Ufa
country: Russian Federation
city: Vologda
country: Russian Federation
city: Barakaldo
country: Spain
city: Barcelona
country: Spain
city: Castellon
country: Spain
city: Hospitalet de Llobregat
country: Spain
city: Las Palmas de Gran Canaria
country: Spain
city: Madrid
country: Spain
city: Málaga
country: Spain
city: Reus
country: Spain
city: Santiago de Compostela
country: Spain
city: Sevilla
country: Spain
city: Stockholm
country: Sweden
city: Umeå
country: Sweden
city: Örebro
country: Sweden
city: Kaohsiung
country: Taiwan
city: Taichung
country: Taiwan
city: Tainan
country: Taiwan
city: Taipei City
country: Taiwan
city: Taipei
country: Taiwan
city: Taoyuan
country: Taiwan
city: Adana
country: Turkey
city: Ankara
country: Turkey
city: Edirne
country: Turkey
city: Istanbul
country: Turkey
city: Izmir
country: Turkey
city: Kayseri
country: Turkey
city: Kocaeli
country: Turkey
city: Dnipro
country: Ukraine
city: Khakhiv
country: Ukraine
city: Kyiv
country: Ukraine
city: Lviv
country: Ukraine
city: Aberdeen
country: United Kingdom
city: Birmingham
country: United Kingdom
city: Bristol
country: United Kingdom
city: Derby
country: United Kingdom
city: Glasgow
country: United Kingdom
city: Oxford
country: United Kingdom
city: Plymouth
country: United Kingdom
city: Preston
country: United Kingdom
city: Sheffield
country: United Kingdom
city: Sutton
country: United Kingdom
city: Wolverhampton
country: United Kingdom
Study officials:
affiliation: Aragon Pharmaceuticals, Inc.
name: Aragon Pharmaceuticals, Inc. Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Poterala JE, Wisinski KB. Abbreviated endocrine therapy duration for low estrogen receptor-positive breast cancer: The counter to extended endocrine therapy. Cancer. 2022 May 1;128(9):1724-1726. doi: 10.1002/cncr.34158. Epub 2022 Feb 25. No abstract available.