A Study of Adding Apalutamide to Radiotherapy and LHRH Agonist in High-Risk Patients With Hormone-Sensitive Prostate Cancer

Prostatic Neoplasms Clinical Trial

— PRIMORDIUM  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04557059
• Other study ID #: CR108705
• Secondary ID: 56021927PCR30152
• Status: Recruiting
• Phase: Phase 3
• Start date: November 12, 2020
• Est. completion date: August 27, 2029

Study information

• Verified date: March 2024
• Source: Janssen Pharmaceutica N.V., Belgium
• Contact: Study Contact
• Phone: 844-434-4210
• Email: Participate-In-This-Study[@]its.jnj.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 412
• Est. completion date: August 27, 2029
• Est. primary completion date: August 27, 2029
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Prostatic Neoplasms

Intervention

Radiation:
• Radiotherapy
Participants will receive radiotherapy (RT) with or without optional stereotactic body radiation therapy (SBRT), which will start within 4 weeks after randomization.

Drug:
• LHRHa
Participants will be administered with LHRHa (example, leuprolide, goserelin, triptorelin acetate) 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.
• Apalutamide
Participants will receive therapeutic dose of apalutamide 240 mg once daily for 180 Days.

Locations

Country	Name	City	State
Australia	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
Austria	Ordensklinikum Linz GmbH Elisabethinen	Linz
Austria	Universitaetsklinikum Salzburg - Landeskrankenhaus	Salzburg
Austria	Medizinische Universitat Wien	Wien
Belgium	A.Z. Sint Jan	Brugge
Belgium	UZ Gent	Gent
Belgium	Az Groeninge	Kortrijk
Belgium	GZA Ziekenhuis	Wilrijk
Brazil	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 de Senhoras - Hospital Sírio Libanês	São Paulo
Brazil	Sociedade Beneficente Israelita Brasileira Hospital Albert Einstein	São Paulo
Czechia	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
Denmark	Aalborg University Hospital	Aalborg
Denmark	Aarhus University Hospital	Aarhus N.
Denmark	Rigshospitalet	Copenhagen N
Denmark	Gentofte Herlev Hospital	Herlev
Finland	Helsinki University Hospital	Helsinki
Finland	Oulu University Hospital	Oulu
Finland	Tampere University Hospital	Tampere
Finland	Turku University Hospital	Turku
Finland	Vaasa Central Hospital	Vaasa
Germany	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
Hungary	Budapesti Bajcsy Zsilinszky Korhaz es Rendelointezet	Budapest
Hungary	Budapesti Uzsoki Utcai Korhaz	Budapest
Hungary	Eszak Budai Szent Janos Centrumkorhaz	Budapest
Hungary	Jahn Ferenc Del-pesti Korhaz es Rendelointezet	Budapest
Hungary	Orszagos Onkologiai Intezet	Budapest
Hungary	Péterfy Sándor utcai Kórház	Budapest
Hungary	Debreceni Egyetem Klinikai Kozpont	Debrecen
Italy	Radioterapia Oncologica, A.O.U. San'T Orsola	Bologna
Italy	Azienda Ospedaliero Universitaria Careggi	Firenze
Italy	Ospedale San Raffaele	Milano
Italy	Azienda Ospedaliera Sant Andrea	Roma
Italy	Fondazione Policlinico Tor Vergata	Roma
Italy	Istituto Nazionale Tumori Regina Elena	Roma
Jordan	King Hussein Cancer Center	Amman
Lebanon	American Universitty of Beirut Medical Center	Beirut
Lebanon	St Georges Hospital university medical centre	Beirut
Lebanon	Notre Dame De Secours	Jbeil
Lebanon	Centre Hospitalier du Nord	Zgharta
Mexico	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	Centro de Estudio Clínicos de Querétaro S.C.	Queretaro
Poland	Centrum Onkologii im. Prof. F. Lukaszczyka w Bydgoszczy	Bydgoszcz
Poland	NU-MED Grupa S.A Centrum Radioterapii i Usprawniania	Elblag
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk
Poland	Szpitale Pomorskie Sp z o o	Gdynia
Poland	Swietokrzyskie Centrum Onkologii SPZOZ w Kielcach	Kielce
Poland	Szpital Wojewódzki 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
Portugal	Centro Hospitalar Lisboa Ocidental - Hospital São Fracisco Xavier	Lisboa
Portugal	Chln - Hosp. Santa Maria	Lisboa
Portugal	Fundacao Champalimaud	Lisboa
Portugal	Hospital CUF Tejo	Lisboa
Portugal	Hospital da Luz	Lisboa
Portugal	IPO Lisboa	Lisboa
Portugal	Centro Hospitalar Universitario do Porto, EPE	Porto
Portugal	Centro Hospitalar de Entre o Douro e Vouga, E.P.E	Santa Maria da Feira
Russian Federation	SHI Sverdlovsk Regional Clinical Hospital #1	Ekaterinburg
Russian Federation	Ivanovo Regional Oncology Dispensary	Ivanovo
Russian Federation	City Clinical Hospital #57	Moscow
Russian Federation	Hertzen Oncology Research Institute	Moscow
Russian Federation	I.M. Sechenov First Moscow State Medical University	Moscow
Russian Federation	SPb SBIH 'City Clinical Oncological Dispensary'	Saint Petersburg
Russian Federation	Multifunctional clinical medical center 'Medical city'	Tyumen
Slovakia	CUIMED - urologická ambulancia	Bratislava
Slovakia	Východoslovenský Onkologický Ústav	Košice
Slovakia	Univerzitná nemocnica Martin	Martin
Slovakia	Uroexam s.r.o.	Nitra
Slovakia	Urologicka ambulancia e.cho Poprad, s.r.o	Poprad
Slovakia	MILAB s.r.o.	Prešov
Slovakia	Privátna urologická ambulancia	Trencin
Spain	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
Sweden	Urologiska Mottagningen	Malmö
Sweden	Prostatacancercentrum	Stockholm
Sweden	Södersjukhuset	Stockholm
Turkey	Adana Baskent Yuregir Hospital	Adana
Turkey	Ankara University Medical Faculty	Ankara
Turkey	Dr Abdurrahman Yurtaslan Oncology Training and Research Hospital	Ankara
Turkey	Hacettepe University Medical Faculty	Ankara
Turkey	Memorial Ankara Hastanesi	Ankara
Turkey	Bakirkoy Training and Research Hospital	Istanbul
Turkey	Goztepe Prof Dr Suleyman Yalcin Sehir Hastanesi	Istanbul
Turkey	Istanbul University Cerrahpasa Medical Faculty	Istanbul
Turkey	Kartal Dr Lutfi Kirdar Egitim ve Arastirma Hastanesi	Istanbul
Turkey	Dokuz Eylul Universitesi Tip Fakultesi	Izmir
Turkey	Sakarya Üniversitesi Tip Fakültesi Hastanesi	Sakarya
United States	Urology Austin	Austin	Texas
United States	MidLantic Urology	Bala-Cynwyd	Pennsylvania
United States	The Urology Group	Cincinnati	Ohio
United States	Urological Research Network	Hialeah	Florida
United States	Houston Metro Urology	Houston	Texas
United States	First Urology, PSC	Jeffersonville	Indiana
United States	Colorado Clinical Research	Lakewood	Colorado
United States	Arkansas Urology	Little Rock	Arkansas
United States	Spokane Urology	Spokane	Washington
United States	Oregon Urology Institute	Springfield	Oregon
United States	Associated Medical Professionals of Ny	Syracuse	New York
United States	Michigan Institute of Urology	Troy	Michigan
United States	Arizona Urology Specialists	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Pharmaceutica N.V., Belgium

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Brazil,  Czechia,  Denmark,  Finland,  Germany,  Hungary,  Italy,  Jordan,  Lebanon,  Mexico,  Poland,  Portugal,  Russian Federation,  Slovakia,  Spain,  Sweden,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Prostate specific Membrane Antigen-Positron Emission Tomography (PSMA-PET) Metastatic Progression-free Survival (ppMPFS)	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.	Up to 9 years
Secondary	Time to Prostate-Specific Antigen (PSA) Progression	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.	Up to 9 years
Secondary	PSA Response Rate	PSA response rate is defined as the percentage of participants with a PSA decrease of >= 50 percent (%), >= 90% or undetectable from baseline.	Up to 9 years
Secondary	PSA Levels at Week 26	PSA levels at week 26 will be reported.	Week 26
Secondary	Time to Loco-Regional Progression by PSMA-PET	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.	Up to 9 years
Secondary	Overall Survival	Overall survival is defined as the time from randomization to date of death from any cause.	Up to 9 years
Secondary	Prostate Cancer-Specific Survival	Prostate cancer-specific survival is defined as the time from randomization to date of death due to prostate cancer.	Up to 9 years
Secondary	Number of Participants With Adverse Event (AE) and Serious Adverse Events (SAEs)	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.	Up to 9 years