PRIMORDIUM: A Study of Adding Apalutamide to Radiotherapy and LHRH Agonist in High-Risk Patients With Prostate-Specific Membrane Antigen-Positron Emission Tomography (PSMA-PET) Positive Hormone-Sensitive Prostate Cancer Participants

• Sponsor: Janssen Pharmaceutica N.V., Belgium (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT04557059
• Collaborator: (none)
• Enrollment: 412
• Locations: 129
• Arms: 3
• Anticipated Duration (Months): 86
• Patients Per Site: 3.2
• Patients Per Site Per Month: 0

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Prostatic Neoplasms	Radiation: Radiotherapy; Drug: LHRHa; Drug: Apalutamide	Phase 3

Detailed Description

Prostate cancer is currently the fifth leading cause of cancer deaths among men globally, with 1 million diagnosed per year and mortality burden of over 300,000 deaths. The hypothesis of study is addition of apalutamide to RT+ LHRHa provides superior efficacy in terms of PSMA-PET metastatic progression-free survival-ppMPFS. Apalutamide is a non-steroidal androgen receptor (AR) antagonist being developed for the treatment of prostate cancer. RT+LHRHa is a combination therapy, when administered concomitantly, in high-risk patients with BCR relapsing after RP, potentially leads to relevant delay in the metastatic progression of prostate cancer at an early stage of the disease, or even cure in some cases. Study consists of 2 cohorts (intervention and observational cohort). At screening, eligible participants will undergo prostate-specific membrane antigen-positron emission tomography (PSMA-PET), whole-body Tc-bone scan, computed tomography (CT). Interventional Cohort, consisting of PSMA-PET positive participants, will undergoes 3 phases: Treatment Phase, a Post-treatment Phase and a Post-PSMA-PET Progression Phase. After 6-month Treatment Phase, participants will be prospectively assessed in Post-treatment Phase until PSMA-PET-positive metastatic progression is confirmed. Observational cohort will run parallelly to interventional cohort. PSMA-PET negative, participants will be observed until time-point when number of events required for analysis of primary endpoint is reached in Interventional Cohort. This cohort provides an approach to document the selection of treatments and observation of interventions in a real-life clinical practice setting. The duration of the study is estimated to be approximately 7 years.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 412 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 PSMA-PET-Positive Hormone-Sensitive Prostate Cancer, With an Observational Follow-up of PSMA-PET-Negative Patients
• Actual Study Start Date: Nov 12, 2020
• Anticipated Primary Completion Date: Jan 14, 2028
• Anticipated Study Completion Date: Jan 14, 2028

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Interventional Cohort (Group 1): RT+ LHRHa Participants who are PSMA-PET-positive 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.	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.
Experimental: Interventional Cohort (Group 2): RT+LHRHa + Apalutamide Participants who are PSMA-PET-positive 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.	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.; Drug: Apalutamide; Participants will receive therapeutic dose of apalutamide 240 mg once daily for 180 Days.; Other Names: JNJ-56021927
No Intervention: Observational Cohort(Group3) PSMA-PET Negative Participants Participants who are PSMA-PET-negative at screening, will be enrolled in the Observational Cohort. Data collected in the course of routine clinical practice during this period will include clinical evaluations, disease progression, therapies administered as per standard-of-care at the study-sites and survival status. For Observational Cohort, information will be entered into the electronic case report form (eCRF) from the medical records at least twice a year.

Outcome Measures

Primary Outcome Measures

1. Prostate specific Membrane Antigen-Positron Emission Tomography (PSMA-PET) Metastatic Progression-free Survival (ppMPFS) [Up to 7 years]

   ppMPFS is defined as the appearance of at least 1 new PSMA-PET-positive distant lesion compared with the previous scan as assessed by blinded independent central review (BICR) or death.

Secondary Outcome Measures

1. Time to Prostate-Specific Antigen (PSA) Progression [Up to 7 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 repeated measurement at least 3 Weeks later.

2. PSA Response Rate [Up to 7 years]

   PSA response rate is defined as the percentage of participants with a PSA decrease of >= 50 percent (%), >= 90% or undetectable from baseline.

3. PSA Levels at Week 26 [Week 26]

   PSA levels at week 26 will be reported.

4. Time to Loco-Regional Progression by PSMA-PET [Up to 7 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.

5. Overall Survival [Up to 7 years]

   Overall survival is defined as the time from randomization to date of death from any cause.

6. Prostate Cancer-Specific Survival [Up to 7 years]

   Prostate cancer-specific survival is defined as the time from randomization to date of death due to prostate cancer.

7. Number of Participants With Adverse Event (AE) and Serious Adverse Events (SAEs) [Up to 7 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologically confirmed adenocarcinoma of the prostate

• Previously treated with radical prostatectomy with or without lymph node dissection and any post-operative prostate-specific antigen (PSA) measurement of less than (<) 0.1 nanogram/milliliter (ng/mL) between Week 6 and Week 20

• Be able to swallow whole the study drug tablets or follow the instructions for admixing with apple sauce

• Prostate specific membrane antigen-positron emission tomography (PSMA-PET) must be performed at screening: Patients who are PSMA-PET-positive for at least one loco-regional (pelvic) lesion with or without distant (extra-pelvic) lesions at screening, as determined by Blinded Independent Central Review (BICR), will be eligible to be randomized to either arm of the Interventional Cohort.The investigators will be blinded to the location of the PSMA-PET lesions after randomization and patients who are PSMA-PET-negative for any prostate cancer lesions (that is no loco-regional lesion and no distant lesion) at screening, as determined by BICR, will be eligible for inclusion in the Observational Cohort

• Biochemically recurrent prostate cancer after RP with a high risk of developing metastasis defined as pathological Gleason score greater than or equal to (>=) 8 evaluated from prostate tissue specimen at radical prostatectomy, OR PSADT less than or equal to (<=) 12 months at the time of screening

• 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 patient should be excluded from the study. Conventional images (99mTc-bone scan and CT/MRI) from the screening will be sent to BICR for confirmation of non-metastatic prostate cancer 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) prostate cancer (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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Flinders Medical Centre	Bedford Park		Australia	5042
2	Bundaberg Hospital	Bundaberg		Australia	4670
3	Hervey Bay Hospital	Bundaberg		Australia	4670
4	Epworth Healthcare	East Melbourne		Australia	3002
5	St Vincent's Hospital - Melbourne	Fitzroy		Australia	3065
6	Genesis Care Hurstville	Hurstville		Australia	2220
7	Macquarie University Hospital	North Ryde		Australia	2109
8	Calvary Mater Newcastle	Waratah		Australia	2298
9	GenesisCare Wembley	Wembley		Australia	6014
10	Medical University Innsbruck	Innsbruck		Austria	6020
11	Ordensklinikum Linz GmbH Elisabethinen	Linz		Austria	4020
12	Universitätsklinikum Salzburg - Landeskrankenhaus	Salzburg		Austria	5020
13	Medizinische Universität Wien	Wien		Austria	1090
14	A.Z. Sint Jan	Brugge		Belgium	8000
15	UZ Gent	Gent		Belgium	9000
16	Az Groeninge	Kortrijk		Belgium	8500
17	GZA Ziekenhuis	Wilrijk		Belgium	2610
18	Cetus Oncologia	Belo Horizonte		Brazil	30110-022
19	Hospital Erasto Gaertner	Curitiba		Brazil	81520-060
20	Liga Norte Riograndense Contra O Cancer	Natal		Brazil	59075-740
21	Hospital Moinhos de Vento	Porto Alegre		Brazil	90035-901
22	Irmandade da Santa Casa de Misericordia de Porto Alegre	Porto Alegre		Brazil	90050-170
23	Hospital Sao Rafael	Salvador		Brazil	41253-190
24	Hospital Alemão Oswaldo Cruz	Sao Paulo		Brazil	01421-000
25	Hospital Sao Camilo Unidade Vila Mariana	Sao Paulo		Brazil	04014-002
26	Sociedade Beneficiante de Senhoras - Hospital Sirio Libanes	São Paulo		Brazil	01308-050
27	Hospital Israelita Albert Einstein	São Paulo		Brazil	05652-900
28	Fakultni nemocnice Plzen, Urologicka klinika	Plzen		Czechia	305 99
29	Urocentrum Praha	Praha 2		Czechia	120 00
30	Urologicka klinika 1.LF UK a VFN	Praha 2		Czechia	120 00
31	Fakultni nemocnice v Motole	Praha 5		Czechia	15006
32	Aalborg University Hospital	Aalborg		Denmark	9000
33	Aarhus University Hospital	Aarhus N.		Denmark	8200
34	Rigshospitalet	Copenhagen N		Denmark	2200
35	Gentofte Herlev Hospital	Herlev		Denmark	2730
36	Helsinki University Hospital	Helsinki		Finland	290
37	Oulu University Hospital	Oulu		Finland	90029
38	Tampere University Hospital	Tampere		Finland	33520
39	Turku University Hospital	Turku		Finland	20520
40	Vaasa Central Hospital	Vaasa		Finland	65130
41	Péterfy Sándor utcai Kórház	Budapest		Hungary	1076
42	Bajcsy-Zsilinszky Kórház és Rendelőintézet	Budapest		Hungary	1106
43	Orszagos Onkologiai Intezet	Budapest		Hungary	1122
44	Észak-Közép-budai Centrum, Új Szent János Kórház és Szakrendelő Budai Családközpontú	Budapest		Hungary	1125
45	Uzsoki Utcai Korhaz	Budapest		Hungary	1145
46	Jahn Ferenc Del-pesti Korhaz es Rendelointezet	Budapest		Hungary	1204
47	Debreceni Egyetem Klinikai Kozpont	Debrecen		Hungary	4032
48	Radioterapia Oncologica, A.O.U. San'T Orsola	Bologna		Italy	40138
49	Azienda Ospedaliero Universitaria Careggi	Firenze		Italy	50134
50	Ospedale San Raffaele	Milano		Italy	20132
51	Fondazione Policlinico Tor Vergata	Roma		Italy	00133
52	Istituto Nazionale Tumori Regina Elena	Roma		Italy	00144
53	Azienda Ospedaliera Sant Andrea	Roma		Italy	00189
54	St Georges Hospital university medical centre	Beirut		Lebanon	11 00 2807
55	American Universitty of Beirut Medical Center	Beirut		Lebanon	1107 2020
56	Notre Dame De Secours	Jbeil		Lebanon	3
57	Centre Hospitalier du Nord	Zgharta		Lebanon	100
58	Hospital Aranda de la Parra S.A. de C.V.	Leon		Mexico	37000
59	Avix Investigacion Clinica, S.C.	Monterrey		Mexico	64710
60	Oncologia Integral Satelite	Naucalpan		Mexico	53100
61	Oncocenter	Puebla		Mexico	72530
62	Centro de Estudio Clínicos de Querétaro S.C.	Queretaro		Mexico	76000
63	Centrum Onkologii im. Prof. F. Lukaszczyka w Bydgoszczy	Bydgoszcz		Poland	85-796
64	Uniwersyteckie Centrum Kliniczne	Gdansk		Poland	80-952
65	Szpitale Pomorskie Sp. z o.o.	Gdynia		Poland	81-519
66	Swietokrzyskie Centrum Onkologii SPZOZ w Kielcach	Kielce		Poland	25-734
67	Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Lodzi	Lodz		Poland	93-513
68	Radomskie Centrum Onkologii	Radom		Poland	26-600
69	Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy	Warszawa		Poland	02-781
70	IPO Lisboa	Lisboa		Portugal	1099-023
71	Hospital CUF Tejo	Lisboa		Portugal	1350-352
72	Fundação Champalimaud	Lisboa		Portugal	1400-038
73	Centro Hospitalar Lisboa Ocidental - Hospital São Fracisco Xavier	Lisboa		Portugal	1449-005
74	Hospital da Luz	Lisboa		Portugal	1500-650
75	Chln - Hosp. Santa Maria	Lisboa		Portugal	1649-035
76	Centro Hospitalar Universitario do Porto, EPE	Porto		Portugal	4099-001
77	Instituto Portugues de Oncologia	Porto		Portugal	4200072
78	Centro Hospitalar de Entre o Douro e Vouga, E.P.E	Santa Maria da Feira		Portugal	4520-211
79	SHI Sverdlovsk Regional Clinical Hospital #1	Ekaterinburg		Russian Federation	620102
80	Ivanovo Regional Oncology Dispensary	Ivanovo		Russian Federation	153040
81	City Clinical Hospital #57	Moscow		Russian Federation	105077
82	FSBSI 'N. N. Blokhin Russian Cancer Research Center'	Moscow		Russian Federation	115478
83	Russian Scientific Center of Roentgenoradiology	Moscow		Russian Federation	117997
84	I.M. Sechenov First Moscow State Medical University	Moscow		Russian Federation	119991
85	Central Clinical Hospital	Moscow		Russian Federation	121359
86	Hertzen Oncology Research Institute	Moscow		Russian Federation	125284
87	Privolzhsky District Medical Center under the Federal Medico-Biological Agency	Nizhni Novgorod		Russian Federation	603109
88	Clinical Oncology Dispensary	Omsk		Russian Federation	644013
89	LLC Novaya Clinica	Pyatigorsk		Russian Federation	357500
90	Private Medical Institution Euromedservice	Saint Petersburg		Russian Federation	196603
91	SPb SBIH 'City Clinical Oncological Dispensary'	Saint Petersburg		Russian Federation	197022
92	Leningrad Regional Oncology Dispensary	Saint-Petersburg		Russian Federation	191104
93	Clinical hopital n/a Petra velikogo	Saint-Petersburg		Russian Federation	195067
94	Russian Scientific Center of Radiology and Surgical Technologies	Sankt-Peterburg		Russian Federation	197758
95	Multifunctional clinical medical center 'Medical city'	Tyumen		Russian Federation	625041
96	FNsP F.D.R. Banska Bystrica	Banska Bystrica		Slovakia	974 01
97	CUIMED - urologická ambulancia	Bratislava		Slovakia	851 05
98	Východoslovenský Onkologický Ústav	Košice		Slovakia	04191
99	Univerzitná nemocnica Martin	Martin		Slovakia	036 59
100	Uroexam s.r.o.	Nitra		Slovakia	94901
101	Urologicka ambulancia e.cho Poprad, s.r.o	Poprad		Slovakia	05801
102	MILAB s.r.o.	Prešov		Slovakia	08001
103	Privátna urologická ambulancia	Trencin		Slovakia	911 01
104	Hospital Universitario Puerto Del Mar	Cadiz		Spain	11009
105	Hosp. Arquitecto Marcide	Ferrol		Spain	15405
106	Hosp. de Jerez de La Frontera	Jerez de la Frontera		Spain	11407
107	Hosp. Univ. 12 de Octubre	Madrid		Spain	28041
108	Hosp. Univ. de La Paz	Madrid		Spain	28046
109	Hosp. Virgen de La Victoria	Málaga		Spain	29010
110	Complejo Hosp. de Navarra	Navarra		Spain	31008
111	Clinica Univ. de Navarra	Pamplona		Spain	31008
112	Hosp. Virgen Del Rocio	Sevilla		Spain	41013
113	Hosp. Clinico Univ. Lozano Blesa	Zaragoza		Spain	50009
114	Hosp. Univ. Miguel Servet	Zaragoza		Spain	50009
115	Urologiska Mottagningen	Malmö		Sweden	205 02
116	Prostatacancercentrum	Stockholm		Sweden	112 18
117	Södersjukhuset	Stockholm		Sweden	11883
118	Adana Baskent Yuregir Hospital	Adana		Turkey	01250
119	Hacettepe University Medical Faculty	Ankara		Turkey	06230
120	Memorial Ankara Hastanesi	Ankara		Turkey	06520
121	Ankara University Medical Faculty	Ankara		Turkey	06590
122	Dr.Abdurrahman Yurtaslan Oncology Training and Research Hospital	Ankara		Turkey	6200
123	Koc University, School of Medicine, Koc University Hospital	Istanbul		Turkey	34010
124	Istanbul University Cerrahpasa Medical Faculty	Istanbul		Turkey	34096
125	Bakirkoy Training and Research Hospital	Istanbul		Turkey	34147
126	Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi	Istanbul		Turkey	34722
127	Kartal Dr. Lutfi Kirdar Egitim ve Arastirma Hastanesi	Istanbul		Turkey	34890
128	Dokuz Eylul Universitesi Tip Fakultesi	Izmir		Turkey	35340
129	Sakarya Üniversitesi Tıp Fakültesi Hastanesi	Sakarya		Turkey	54187

Sponsors and Collaborators

• Janssen Pharmaceutica N.V., Belgium

Investigators

• Study Director: Janssen Pharmaceutica N.V., Belgium Clinical Trial, Janssen Pharmaceutica N.V., Belgium

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Janssen Pharmaceutica N.V., Belgium
• ClinicalTrials.gov Identifier: NCT04557059
• Other Study ID Numbers: CR108705; 56021927PCR3015; 2019-002957-46
• First Posted: Sep 21, 2020
• Last Update Posted: Aug 3, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Prostatic Neoplasms

Study Results

No Results Posted as of Aug 3, 2022