A Study of Adding Apalutamide to Radiotherapy and LHRH Agonist in High-Risk Patients With Hormone-Sensitive Prostate Cancer
- Conditions
- Prostatic Neoplasms
- Interventions
- Registration Number
- NCT04557059
- Lead Sponsor
- Janssen Pharmaceutica N.V., Belgium
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- Male
- Target Recruitment
- 694
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Interventional Cohort (Group 2): RT+LHRHa + Apalutamide Radiotherapy Participants will receive prostate-bed plus pelvic lymph node salvage external-beam radiotherapy (RT) with or without optional stereotactic body radiation therapy (SBRT), along with a LHRHa as a 3-monthly depot preparation within 3 days after randomization and the end of Week 12, or as a 6-monthly depot preparation within 3 days after randomization. Participants will also receive 240 milligram (mg) of apalutamide starting within 3 days after randomization as film-coated tablets, to be swallowed whole and together once daily with or without food, for a period of 180 Days. Interventional Cohort (Group 1): RT+ LHRHa Radiotherapy Participants will receive radiotherapy (RT) which is defined as prostate-bed plus pelvic lymph node salvage external-beam radiotherapy with or without optional stereotactic body radiation therapy (SBRT), along with a luteinizing hormone-releasing hormone agonist (LHRHa) as a 3-monthly depot preparation within 3 days after randomization and the end of Week 12, or as a 6-monthly depot preparation within 3 days after randomization. Interventional Cohort (Group 1): RT+ LHRHa LHRHa Participants will receive radiotherapy (RT) which is defined as prostate-bed plus pelvic lymph node salvage external-beam radiotherapy with or without optional stereotactic body radiation therapy (SBRT), along with a luteinizing hormone-releasing hormone agonist (LHRHa) as a 3-monthly depot preparation within 3 days after randomization and the end of Week 12, or as a 6-monthly depot preparation within 3 days after randomization. Interventional Cohort (Group 2): RT+LHRHa + Apalutamide LHRHa Participants will receive prostate-bed plus pelvic lymph node salvage external-beam radiotherapy (RT) with or without optional stereotactic body radiation therapy (SBRT), along with a LHRHa as a 3-monthly depot preparation within 3 days after randomization and the end of Week 12, or as a 6-monthly depot preparation within 3 days after randomization. Participants will also receive 240 milligram (mg) of apalutamide starting within 3 days after randomization as film-coated tablets, to be swallowed whole and together once daily with or without food, for a period of 180 Days. Interventional Cohort (Group 2): RT+LHRHa + Apalutamide Apalutamide Participants will receive prostate-bed plus pelvic lymph node salvage external-beam radiotherapy (RT) with or without optional stereotactic body radiation therapy (SBRT), along with a LHRHa as a 3-monthly depot preparation within 3 days after randomization and the end of Week 12, or as a 6-monthly depot preparation within 3 days after randomization. Participants will also receive 240 milligram (mg) of apalutamide starting within 3 days after randomization as film-coated tablets, to be swallowed whole and together once daily with or without food, for a period of 180 Days.
- Primary Outcome Measures
Name Time Method Prostate specific Membrane Antigen-Positron Emission Tomography (PSMA-PET) Metastatic Progression-free Survival (ppMPFS) Up to 9 years ppMPFS is defined as the appearance of at least one new PSMA-PET-positive distant lesion compared with the previous scan as assessed by blinded independent central review (BICR) or death.
- Secondary Outcome Measures
Name Time Method PSA Response Rate Up to 9 years PSA response rate is defined as the percentage of participants with a PSA decrease of \>= 50 percent (%), \>= 90% or undetectable from baseline.
PSA Levels at Week 26 Week 26 PSA levels at week 26 will be reported.
Prostate Cancer-Specific Survival Up to 9 years Prostate cancer-specific survival is defined as the time from randomization to date of death due to prostate cancer.
Number of Participants With Adverse Event (AE) and Serious Adverse Events (SAEs) Up to 9 years An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the study vaccine. An AE can therefore be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal (investigational or non-investigational) product, whether or not related to that medicinal (investigational or non-investigational) product. An SAE is any AE that results in: death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect and is a suspected transmission of any infectious agent via a medicinal product.
Overall Survival Up to 9 years Overall survival is defined as the time from randomization to date of death from any cause.
Time to Prostate-Specific Antigen (PSA) Progression Up to 9 years Time to PSA progression is defined as the time from randomization to the date of first documentation of PSA progression. PSA progression is defined as a PSA concentration above the nadir of more than 0.5 nanogram per milliliter (ng/mL), confirmed by additional measurement at least 3 Weeks later.
Time to Loco-Regional Progression by PSMA-PET Up to 9 years Time to loco-regional progression by PSMA-PET as assessed by blinded independent central review (BCIR) is defined as the time from randomization to the date of the first occurrence of PSMA-PET loco-regional progression. Criteria for PSMA-PET loco-regional progression: Appearance of at least one new PSMA-PET-positive loco-regional lesion compared with the previous scan.
Trial Locations
- Locations (141)
Tampere University Hospital
🇫🇮Tampere, Finland
Turku University Hospital
🇫🇮Turku, Finland
Fondazione Policlinico Tor Vergata
🇮🇹Roma, Italy
Istituto Nazionale Tumori Regina Elena
🇮🇹Roma, Italy
Azienda Ospedaliera Sant Andrea
🇮🇹Roma, Italy
King Hussein Cancer Center
🇯🇴Amman, Jordan
St Georges Hospital university medical centre
🇱🇧Beirut, Lebanon
American Universitty of Beirut Medical Center
🇱🇧Beirut, Lebanon
Notre Dame De Secours
🇱🇧Jbeil, Lebanon
Centre Hospitalier du Nord
🇱🇧Zgharta, Lebanon
Consultorio de Especialidad en Urologia Privado
🇲🇽Durango, Mexico
Hospital Aranda de la Parra S A de C V
🇲🇽Leon, Mexico
Avix Investigacion Clinica S C
🇲🇽Monterrey, Mexico
Oncologia Integral Satelite
🇲🇽Naucalpan, Mexico
Centro de Investigacion Clinica de Oaxaca
🇲🇽Oaxaca de Juárez, Mexico
Oncocenter
🇲🇽Puebla, Mexico
Cuidados Oncologicos
🇲🇽Queretaro, Mexico
Centrum Onkologii im Prof F Lukaszczyka w Bydgoszczy
🇵🇱Bydgoszcz, Poland
NU-MED Grupa S.A Centrum Radioterapii i Onkologii
🇵🇱Elblag, Poland
Uniwersyteckie Centrum Kliniczne
🇵🇱Gdansk, Poland
Szpitale Pomorskie Sp z o o
🇵🇱Gdynia, Poland
Swietokrzyskie Centrum Onkologii SPZOZ w Kielcach
🇵🇱Kielce, Poland
Szpital Wojewodzki im Mikolaja Kopernika w Koszalinie
🇵🇱Koszalin, Poland
Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im M Kopernika w Lodzi
🇵🇱Lodz, Poland
Radomskie Centrum Onkologii
🇵🇱Radom, Poland
Narodowy Instytut Onkologii im Marii Sklodowskiej Curie Panstwowy Instytut Badawczy
🇵🇱Warszawa, Poland
Ipo Lisboa
🇵🇹Lisboa, Portugal
Hosp. Cuf Tejo
🇵🇹Lisboa, Portugal
Fund. Champalimaud
🇵🇹Lisboa, Portugal
Uls Lisboa Ocidental - Hosp. Sao Francisco Xavier
🇵🇹Lisboa, Portugal
Hosp. Da Luz Lisboa
🇵🇹Lisboa, Portugal
Uls Santa Maria - Hosp. Santa Maria
🇵🇹Lisboa, Portugal
Uls Santo Antonio - Hosp. Santo Antonio
🇵🇹Porto, Portugal
Uls de Entre Douro E Vouga - Hosp. Sao Sebastiao
🇵🇹Santa Maria da Feira, Portugal
SHI Sverdlovsk Regional Clinical Hospital #1
🇷🇺Ekaterinburg, Russian Federation
Ivanovo Regional Oncology Dispensary
🇷🇺Ivanovo, Russian Federation
City Clinical Hospital #57
🇷🇺Moscow, Russian Federation
I.M. Sechenov First Moscow State Medical University
🇷🇺Moscow, Russian Federation
Hertzen Oncology Research Institute
🇷🇺Moscow, Russian Federation
SPb SBIH 'City Clinical Oncological Dispensary'
🇷🇺Saint Petersburg, Russian Federation
Multifunctional clinical medical center 'Medical city'
🇷🇺Tyumen, Russian Federation
Univerzitná nemocnica Martin
🇸🇰Martin, Slovakia
Urologicka ambulancia e.cho Poprad, s.r.o
🇸🇰Poprad, Slovakia
Leningrad Regional Oncology Dispensary
🇷🇺Saint-Petersburg, Russian Federation
Uroexam s.r.o.
🇸🇰Nitra, Slovakia
CUIMED - urologická ambulancia
🇸🇰Bratislava, Slovakia
Východoslovenský Onkologický Ústav
🇸🇰Košice, Slovakia
MILAB s.r.o.
🇸🇰Prešov, Slovakia
Privátna urologická ambulancia
🇸🇰Trencin, Slovakia
Hospital Universitario Puerto Del Mar
🇪🇸Cadiz, Spain
Hosp. Arquitecto Marcide
🇪🇸Ferrol, Spain
Hosp. de Jerez de La Frontera
🇪🇸Jerez de la Frontera, Spain
Hosp. Univ. 12 de Octubre
🇪🇸Madrid, Spain
Hosp. Univ. de La Paz
🇪🇸Madrid, Spain
Hosp Virgen de La Victoria
🇪🇸Málaga, Spain
Complejo Hosp. de Navarra
🇪🇸Navarra, Spain
Clinica Univ. de Navarra
🇪🇸Pamplona, Spain
Hosp. Virgen Del Rocio
🇪🇸Sevilla, Spain
Hosp. Univ. I Politecni La Fe
🇪🇸Valencia, Spain
Hosp. Clinico Univ. Lozano Blesa
🇪🇸Zaragoza, Spain
Urologiska Mottagningen
🇸🇪Malmö, Sweden
Prostatacancercentrum
🇸🇪Stockholm, Sweden
Sodersjukhuset
🇸🇪Stockholm, Sweden
Adana Baskent Yuregir Hospital
🇹🇷Adana, Turkey
Hacettepe University Medical Faculty
🇹🇷Ankara, Turkey
Memorial Ankara Hastanesi
🇹🇷Ankara, Turkey
Ankara University Medical Faculty
🇹🇷Ankara, Turkey
Dr Abdurrahman Yurtaslan Oncology Training and Research Hospital
🇹🇷Ankara, Turkey
Koc University, School of Medicine, Koc University Hospital
🇹🇷Istanbul, Turkey
Istanbul University Cerrahpasa Medical Faculty
🇹🇷Istanbul, Turkey
Bakirkoy Training and Research Hospital
🇹🇷Istanbul, Turkey
Goztepe Prof Dr Suleyman Yalcin Sehir Hastanesi
🇹🇷Istanbul, Turkey
Kartal Dr Lutfi Kirdar Egitim ve Arastirma Hastanesi
🇹🇷Istanbul, Turkey
Dokuz Eylul Universitesi Tip Fakultesi
🇹🇷Izmir, Turkey
Sakarya Üniversitesi Tıp Fakültesi Hastanesi
🇹🇷Sakarya, Turkey
Arizona Urology Specialists
🇺🇸Tucson, Arizona, United States
Arkansas Urology
🇺🇸Little Rock, Arkansas, United States
Colorado Clinical Research
🇺🇸Lakewood, Colorado, United States
Urological Research Network
🇺🇸Hialeah, Florida, United States
First Urology, PSC
🇺🇸Jeffersonville, Indiana, United States
Michigan Institute of Urology
🇺🇸Troy, Michigan, United States
The Urology Group
🇺🇸Cincinnati, Ohio, United States
Associated Medical Professionals of Ny
🇺🇸Syracuse, New York, United States
Oregon Urology Institute
🇺🇸Springfield, Oregon, United States
MidLantic Urology
🇺🇸Bala-Cynwyd, Pennsylvania, United States
Urology Austin
🇺🇸Austin, Texas, United States
Houston Metro Urology
🇺🇸Houston, Texas, United States
Spokane Urology
🇺🇸Spokane, Washington, United States
Bundaberg Hospital
🇦🇺Bundaberg, Australia
Hervey Bay Hospital
🇦🇺Bundaberg, Australia
Epworth Healthcare
🇦🇺East Melbourne, Australia
St Vincent's Hospital - Melbourne
🇦🇺Fitzroy, Australia
Genesis Care Hurstville
🇦🇺Hurstville, Australia
Macquarie University Hospital
🇦🇺North Ryde, Australia
Calvary Mater Newcastle
🇦🇺Waratah, Australia
GenesisCare Wembley
🇦🇺Wembley, Australia
Ordensklinikum Linz GmbH Elisabethinen
🇦🇹Linz, Austria
Universitaetsklinikum Salzburg Landeskrankenhaus
🇦🇹Salzburg, Austria
Medizinische Universitaet Wien
🇦🇹Wien, Austria
A.Z. Sint Jan
🇧🇪Brugge, Belgium
UZ Gent
🇧🇪Gent, Belgium
Az Groeninge
🇧🇪Kortrijk, Belgium
GZA Ziekenhuis
🇧🇪Wilrijk, Belgium
Empresa Brasileira de Servicos Hospitalares - EBSERH - Hospital das Clinicas da UFMG
🇧🇷Belo Horizonte, Brazil
Liga Paranaense de Combate ao Cancer
🇧🇷Curitiba, Brazil
Liga Norte Riograndense Contra O Cancer
🇧🇷Natal, Brazil
Associacao Hospitalar Moinhos de Vento
🇧🇷Porto Alegre, Brazil
Irmandade Santa Casa de Misericordia de Porto Alegre
🇧🇷Porto Alegre, Brazil
Oncoclinicas Rio de Janeiro S A
🇧🇷Rio de Janeiro, Brazil
Hospital Sao Rafael
🇧🇷Salvador, Brazil
Hospital Alemao Oswaldo Cruz
🇧🇷Sao Paulo, Brazil
Hospital Sao Camilo Unidade Vila Mariana
🇧🇷Sao Paulo, Brazil
Sociedade Beneficente Israelita Brasileira Hospital Albert Einstein
🇧🇷Sao Paulo, Brazil
Sociedade Beneficente de Senhoras Hospital Sirio Libanes
🇧🇷São Paulo, Brazil
Fakultni nemocnice Plzen, Urologicka klinika
🇨🇿Plzen, Czechia
Urocentrum Praha
🇨🇿Praha 2, Czechia
Urologicka klinika 1 LF UK a VFN
🇨🇿Praha 2, Czechia
Fakultni nemocnice v Motole
🇨🇿Praha 5, Czechia
Aalborg University Hospital
🇩🇰Aalborg, Denmark
Aarhus University Hospital
🇩🇰Aarhus N., Denmark
Rigshospitalet
🇩🇰Copenhagen N, Denmark
Gentofte Herlev Hospital
🇩🇰Herlev, Denmark
Helsinki University Hospital
🇫🇮Helsinki, Finland
Oulu University Hospital
🇫🇮Oulu, Finland
Orszagos Onkologiai Intezet
ðŸ‡ðŸ‡ºBudapest, Hungary
Eszak Budai Szent Janos Centrumkorhaz
ðŸ‡ðŸ‡ºBudapest, Hungary
Budapesti Uzsoki Utcai Korhaz
ðŸ‡ðŸ‡ºBudapest, Hungary
Jahn Ferenc Del-pesti Korhaz es Rendelointezet
ðŸ‡ðŸ‡ºBudapest, Hungary
Debreceni Egyetem Klinikai Kozpont
ðŸ‡ðŸ‡ºDebrecen, Hungary
Radioterapia Oncologica, A.O.U. San'T Orsola
🇮🇹Bologna, Italy
Azienda Ospedaliero Universitaria Careggi
🇮🇹Firenze, Italy
Ospedale San Raffaele
🇮🇹Milano, Italy
Vaasa Central Hospital
🇫🇮Vaasa, Finland
Vivantes Klinikum Am Urban
🇩🇪Berlin, Germany
Städtisches Klinikum Braunschweig gGmbH - Standort Salzdahlumer
🇩🇪Braunschweig, Germany
Universitatsklinikum Carl Gustav Carcus Dresden
🇩🇪Dresden, Germany
Universitatsklinikum Essen
🇩🇪Essen, Germany
Universitaetsklinikum Muenster
🇩🇪Muenster, Germany
Klinikum rechts der Isar - der Technischen Universität München
🇩🇪Munchen, Germany
Péterfy Sándor utcai Kórház
ðŸ‡ðŸ‡ºBudapest, Hungary
Budapesti Bajcsy Zsilinszky Korhaz es Rendelointezet
ðŸ‡ðŸ‡ºBudapest, Hungary