Clinical trial NCT04557059: A Study of Adding Apalutamide to Radiotherapy and LHRH Agonist in High-Risk Patients With Hormone-Sensitive Prostate Cancer
Official title: A Randomized, Controlled, Multicenter, Open-label Study to Investigate the Efficacy and Safety of Adding Apalutamide to Radiotherapy and LHRH Agonist in High-Risk Patients With Hormone-Sensitive Prostate Cancer, Assessed by PSMA-PET With an Observational Cohort
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Prostatic Neoplasms
Lead sponsor: Janssen Pharmaceutica N.V., Belgium
Sponsor class: INDUSTRY
First posted: 2020-09-21
Enrollment: 694
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 main purpose of this study is to determine if the addition of apalutamide to radiotherapy (RT) plus luteinizing hormone-releasing hormone agonist (LHRHa) delays metastatic progression as assessed by prostate specific membrane antigen-positron emission tomography (PSMA-PET) or death compared with RT plus LHRHa alone.


Eligibility criteria: Inclusion Criteria:

* Histologically confirmed adenocarcinoma of the prostate
* Previously treated with radical prostatectomy with or without lymph node dissection and either: a) for biochemical recurrence after radical prostatectomy (RP): any post-operative prostate-specific antigen (PSA) measurement of less than (\<) 0.1 nanogram/milliliter (ng/mL) within 12 months after RP and without any PSA greater than and equal to (\>=) 0.1 ng/mL within the 4 to 8-week period after RP or b) for persistent PSA after RP: PSA \>=0.1 ng/mL within the 4 to 8-week period after RP, confirmed by additional measurement at least 3 weeks later
* Be able to swallow whole the study drug tablets or follow the instructions for admixing with apple sauce
* Results of the Prostate specific membrane antigen-positron emission tomography (PSMA-PET) at screening as determined by blinded independent, central review (BICR), must be: PSMA-PET-negative for any prostate cancer lesions (that is, no loco-regional lesion and no distant lesions); or PSMA-PET-positive for at least one loco-regional (pelvic) lesion without distant extra-pelvic lesion; or PSMA PET- positive for at least one loco--regional (pelvic) lesion with extra-pelvic lesion(s).
* High risk of developing metastasis defined as; a) for biochemical recurrence after RP: pathological Gleason score greater than or equal to (\>=) 8 evaluated from prostate tissue specimen at radical prostatectomy, or prostate-specific antigen doubling time (PSADT) less than or equal to (\<=) 12 months at the time of screening; b) for persistent PSA after RP: pathological Gleason score \>=8, evaluated from prostate tissue specimen at radical prostatectomy
* Participants with evidence of distant metastasis on screening PSMA-PET scan must have no evidence of prostate cancer metastases on screening CT/MRI of the chest/abdomen/pelvis, Technetium 99m \[99mTc\] whole-body bone scan. Participants with a single bone lesion on 99mTc whole-body bone scan should have confirmatory imaging by CT or MRI; if the confirmatory scan confirms the bone lesion, the participant should be excluded from the study. Conventional images (99mTc-bone scan and CT/MRI) from the screening will be evaluated locally before randomization
* Eastern Cooperative Oncology Group Performance Status Grade 0 or 1

Exclusion Criteria:

* History of pelvic radiation for malignancy
* Previous treatment with androgen deprivation therapy (ADT) for prostate cancer
* Previously treated for biochemical recurrence (BCR) or persistent PSA after RP (previous surgical treatment of one or more loco-regional lesions is allowed)
* Prior treatment with a CYP17 inhibitor (example, oral ketoconazole, orteronel, abiraterone acetate, galeterone) or any androgen receptor (AR) antagonist including bicalutamide, flutamide, nilutamide, apalutamide, enzalutamide or darolutamide and any other medications that may lower androgen levels (estrogens, progestins, aminoglutethimide, etc.), including bilateral orchiectomy
* Known or suspected contraindications or hypersensitivity to apalutamide, Luteinizing Hormone-Releasing Hormone (LHRH) agonist or any of the components of the formulations
* Prior chemotherapy for prostate cancer
* Any evidence of prostate cancer metastasis on computed tomography/magnetic resonance imaging (CT/MRI) of the chest/abdomen/pelvis or 99mTc whole-body bone scan, at any time prior to screening

Primary outcomes:
measure: Prostate specific Membrane Antigen-Positron Emission Tomography (PSMA-PET) Metastatic Progression-free Survival (ppMPFS)
timeFrame: Up to 9 years
Secondary outcomes:
measure: Time to Prostate-Specific Antigen (PSA) Progression
timeFrame: Up to 9 years
measure: PSA Response Rate
timeFrame: Up to 9 years
measure: PSA Levels at Week 26
timeFrame: Week 26
measure: Time to Loco-Regional Progression by PSMA-PET
timeFrame: Up to 9 years
measure: Overall Survival
timeFrame: Up to 9 years
measure: Prostate Cancer-Specific Survival
timeFrame: Up to 9 years
measure: Number of Participants With Adverse Event (AE) and Serious Adverse Events (SAEs)
timeFrame: Up to 9 years
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Arizona Urology Specialists
state: Arizona
city: Little Rock
country: United States
facility: Arkansas Urology
state: Arkansas
city: Lakewood
country: United States
facility: Colorado Clinical Research
state: Colorado
city: Hialeah
country: United States
facility: Urological Research Network
state: Florida
city: Jeffersonville
country: United States
facility: First Urology, PSC
state: Indiana
city: Troy
country: United States
facility: Michigan Institute of Urology
state: Michigan
city: Syracuse
country: United States
facility: Associated Medical Professionals of Ny
state: New York
city: Cincinnati
country: United States
facility: The Urology Group
state: Ohio
city: Springfield
country: United States
facility: Oregon Urology Institute
state: Oregon
city: Bala-Cynwyd
country: United States
facility: MidLantic Urology
state: Pennsylvania
city: Austin
country: United States
facility: Urology Austin
state: Texas
city: Houston
country: United States
facility: Houston Metro Urology
state: Texas
city: Spokane
country: United States
facility: Spokane Urology
state: Washington
city: Bundaberg
country: Australia
facility: Bundaberg Hospital
city: Bundaberg
country: Australia
facility: Hervey Bay Hospital
city: East Melbourne
country: Australia
facility: Epworth Healthcare
city: Fitzroy
country: Australia
facility: St Vincent's Hospital - Melbourne
city: Hurstville
country: Australia
facility: Genesis Care Hurstville
city: North Ryde
country: Australia
facility: Macquarie University Hospital
city: Waratah
country: Australia
facility: Calvary Mater Newcastle
city: Wembley
country: Australia
facility: GenesisCare Wembley
city: Linz
country: Austria
facility: Ordensklinikum Linz GmbH Elisabethinen
city: Salzburg
country: Austria
facility: Universitaetsklinikum Salzburg Landeskrankenhaus
city: Wien
country: Austria
facility: Medizinische Universitaet Wien
city: Brugge
country: Belgium
facility: A.Z. Sint Jan
city: Gent
country: Belgium
facility: UZ Gent
city: Kortrijk
country: Belgium
facility: Az Groeninge
city: Wilrijk
country: Belgium
facility: GZA Ziekenhuis
city: Belo Horizonte
country: Brazil
facility: Empresa Brasileira de Servicos Hospitalares - EBSERH - Hospital das Clinicas da UFMG
city: Curitiba
country: Brazil
facility: Liga Paranaense de Combate ao Cancer
city: Natal
country: Brazil
facility: Liga Norte Riograndense Contra O Cancer
city: Porto Alegre
country: Brazil
facility: Associacao Hospitalar Moinhos de Vento
city: Porto Alegre
country: Brazil
facility: Irmandade Santa Casa de Misericordia de Porto Alegre
city: Rio de Janeiro
country: Brazil
facility: Oncoclinicas Rio de Janeiro S A
city: Salvador
country: Brazil
facility: Hospital Sao Rafael
city: Sao Paulo
country: Brazil
facility: Hospital Alemao Oswaldo Cruz
city: Sao Paulo
country: Brazil
facility: Hospital Sao Camilo Unidade Vila Mariana
city: Sao Paulo
country: Brazil
facility: Sociedade Beneficente Israelita Brasileira Hospital Albert Einstein
city: São Paulo
country: Brazil
facility: Sociedade Beneficente de Senhoras Hospital Sirio Libanes
city: Plzen
country: Czechia
facility: Fakultni nemocnice Plzen, Urologicka klinika
city: Praha 2
country: Czechia
facility: Urocentrum Praha
city: Praha 2
country: Czechia
facility: Urologicka klinika 1 LF UK a VFN
city: Praha 5
country: Czechia
facility: Fakultni nemocnice v Motole
city: Aalborg
country: Denmark
facility: Aalborg University Hospital
city: Aarhus N.
country: Denmark
facility: Aarhus University Hospital
city: Copenhagen N
country: Denmark
facility: Rigshospitalet
city: Herlev
country: Denmark
facility: Gentofte Herlev Hospital
city: Helsinki
country: Finland
facility: Helsinki University Hospital
city: Oulu
country: Finland
facility: Oulu University Hospital
city: Tampere
country: Finland
facility: Tampere University Hospital
city: Turku
country: Finland
facility: Turku University Hospital
city: Vaasa
country: Finland
facility: Vaasa Central Hospital
city: Berlin
country: Germany
facility: Vivantes Klinikum Am Urban
city: Braunschweig
country: Germany
facility: Städtisches Klinikum Braunschweig gGmbH - Standort Salzdahlumer
city: Dresden
country: Germany
facility: Universitatsklinikum Carl Gustav Carcus Dresden
city: Essen
country: Germany
facility: Universitatsklinikum Essen
city: Muenster
country: Germany
facility: Universitaetsklinikum Muenster
city: Munchen
country: Germany
facility: Klinikum rechts der Isar - der Technischen Universität München
city: Budapest
country: Hungary
facility: Péterfy Sándor utcai Kórház
city: Budapest
country: Hungary
facility: Budapesti Bajcsy Zsilinszky Korhaz es Rendelointezet
city: Budapest
country: Hungary
facility: Orszagos Onkologiai Intezet
city: Budapest
country: Hungary
facility: Eszak Budai Szent Janos Centrumkorhaz
city: Budapest
country: Hungary
facility: Budapesti Uzsoki Utcai Korhaz
city: Budapest
country: Hungary
facility: Jahn Ferenc Del-pesti Korhaz es Rendelointezet
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Kozpont
city: Bologna
country: Italy
facility: Radioterapia Oncologica, A.O.U. San'T Orsola
city: Firenze
country: Italy
facility: Azienda Ospedaliero Universitaria Careggi
city: Milano
country: Italy
facility: Ospedale San Raffaele
city: Roma
country: Italy
facility: Fondazione Policlinico Tor Vergata
city: Roma
country: Italy
facility: Istituto Nazionale Tumori Regina Elena
city: Roma
country: Italy
facility: Azienda Ospedaliera Sant Andrea
city: Amman
country: Jordan
facility: King Hussein Cancer Center
city: Beirut
country: Lebanon
facility: St Georges Hospital university medical centre
city: Beirut
country: Lebanon
facility: American Universitty of Beirut Medical Center
city: Jbeil
country: Lebanon
facility: Notre Dame De Secours
city: Zgharta
country: Lebanon
facility: Centre Hospitalier du Nord
city: Durango
country: Mexico
facility: Consultorio de Especialidad en Urologia Privado
city: Leon
country: Mexico
facility: Hospital Aranda de la Parra S A de C V
city: Monterrey
country: Mexico
facility: Avix Investigacion Clinica S C
city: Naucalpan
country: Mexico
facility: Oncologia Integral Satelite
city: Oaxaca de Juárez
country: Mexico
facility: Centro de Investigacion Clinica de Oaxaca
city: Puebla
country: Mexico
facility: Oncocenter
city: Queretaro
country: Mexico
facility: Cuidados Oncologicos
city: Bydgoszcz
country: Poland
facility: Centrum Onkologii im Prof F Lukaszczyka w Bydgoszczy
city: Elblag
country: Poland
facility: NU-MED Grupa S.A Centrum Radioterapii i Onkologii
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Gdynia
country: Poland
facility: Szpitale Pomorskie Sp z o o
city: Kielce
country: Poland
facility: Swietokrzyskie Centrum Onkologii SPZOZ w Kielcach
city: Koszalin
country: Poland
facility: Szpital Wojewodzki im Mikolaja Kopernika w Koszalinie
city: Lodz
country: Poland
facility: Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im M Kopernika w Lodzi
city: Radom
country: Poland
facility: Radomskie Centrum Onkologii
city: Warszawa
country: Poland
facility: Narodowy Instytut Onkologii im Marii Sklodowskiej Curie Panstwowy Instytut Badawczy
city: Lisboa
country: Portugal
facility: Ipo Lisboa
city: Lisboa
country: Portugal
facility: Hosp. Cuf Tejo
city: Lisboa
country: Portugal
facility: Fund. Champalimaud
city: Lisboa
country: Portugal
facility: Uls Lisboa Ocidental - Hosp. Sao Francisco Xavier
city: Lisboa
country: Portugal
facility: Hosp. Da Luz Lisboa
city: Lisboa
country: Portugal
facility: Uls Santa Maria - Hosp. Santa Maria
city: Porto
country: Portugal
facility: Uls Santo Antonio - Hosp. Santo Antonio
city: Santa Maria da Feira
country: Portugal
facility: Uls de Entre Douro E Vouga - Hosp. Sao Sebastiao
city: Ekaterinburg
country: Russian Federation
facility: SHI Sverdlovsk Regional Clinical Hospital #1
city: Ivanovo
country: Russian Federation
facility: Ivanovo Regional Oncology Dispensary
city: Moscow
country: Russian Federation
facility: City Clinical Hospital #57
city: Moscow
country: Russian Federation
facility: I.M. Sechenov First Moscow State Medical University
city: Moscow
country: Russian Federation
facility: Hertzen Oncology Research Institute
city: Saint Petersburg
country: Russian Federation
facility: SPb SBIH 'City Clinical Oncological Dispensary'
city: Saint-Petersburg
country: Russian Federation
facility: Leningrad Regional Oncology Dispensary
city: Tyumen
country: Russian Federation
facility: Multifunctional clinical medical center 'Medical city'
city: Bratislava
country: Slovakia
facility: CUIMED - urologická ambulancia
city: Košice
country: Slovakia
facility: Východoslovenský Onkologický Ústav
city: Martin
country: Slovakia
facility: Univerzitná nemocnica Martin
city: Nitra
country: Slovakia
facility: Uroexam s.r.o.
city: Poprad
country: Slovakia
facility: Urologicka ambulancia e.cho Poprad, s.r.o
city: Prešov
country: Slovakia
facility: MILAB s.r.o.
city: Trencin
country: Slovakia
facility: Privátna urologická ambulancia
city: Cadiz
country: Spain
facility: Hospital Universitario Puerto Del Mar
city: Ferrol
country: Spain
facility: Hosp. Arquitecto Marcide
city: Jerez de la Frontera
country: Spain
facility: Hosp. de Jerez de La Frontera
city: Madrid
country: Spain
facility: Hosp. Univ. 12 de Octubre
city: Madrid
country: Spain
facility: Hosp. Univ. de La Paz
city: Málaga
country: Spain
facility: Hosp Virgen de La Victoria
city: Navarra
country: Spain
facility: Complejo Hosp. de Navarra
city: Pamplona
country: Spain
facility: Clinica Univ. de Navarra
city: Sevilla
country: Spain
facility: Hosp. Virgen Del Rocio
city: Valencia
country: Spain
facility: Hosp. Univ. I Politecni La Fe
city: Zaragoza
country: Spain
facility: Hosp. Clinico Univ. Lozano Blesa
city: Malmö
country: Sweden
facility: Urologiska Mottagningen
city: Stockholm
country: Sweden
facility: Prostatacancercentrum
city: Stockholm
country: Sweden
facility: Sodersjukhuset
city: Adana
country: Turkey
facility: Adana Baskent Yuregir Hospital
city: Ankara
country: Turkey
facility: Hacettepe University Medical Faculty
city: Ankara
country: Turkey
facility: Memorial Ankara Hastanesi
city: Ankara
country: Turkey
facility: Ankara University Medical Faculty
city: Ankara
country: Turkey
facility: Dr Abdurrahman Yurtaslan Oncology Training and Research Hospital
city: Istanbul
country: Turkey
facility: Koc University, School of Medicine, Koc University Hospital
city: Istanbul
country: Turkey
facility: Istanbul University Cerrahpasa Medical Faculty
city: Istanbul
country: Turkey
facility: Bakirkoy Training and Research Hospital
city: Istanbul
country: Turkey
facility: Goztepe Prof Dr Suleyman Yalcin Sehir Hastanesi
city: Istanbul
country: Turkey
facility: Kartal Dr Lutfi Kirdar Egitim ve Arastirma Hastanesi
city: Izmir
country: Turkey
facility: Dokuz Eylul Universitesi Tip Fakultesi
city: Sakarya
country: Turkey
facility: Sakarya Üniversitesi Tıp Fakültesi Hastanesi
Study officials:
affiliation: Janssen Pharmaceutica N.V., Belgium
name: Janssen Pharmaceutica N.V., Belgium Clinical Trial
role: STUDY_DIRECTOR
References: