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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04557059




Registration number
NCT04557059
Ethics application status
Date submitted
17/09/2020
Date registered
21/09/2020
Date last updated
30/04/2021

Titles & IDs
Public title
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
Scientific 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
Secondary ID [1] 0 0
56021927PCR3015
Secondary ID [2] 0 0
CR108705
Universal Trial Number (UTN)
Trial acronym
PRIMORDIUM
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prostatic Neoplasms 0 0
Condition category
Condition code
Cancer 0 0 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Radiotherapy
Treatment: Drugs - LHRHa
Treatment: Drugs - Apalutamide

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 on Day 1 and at Day 85, or as a 6-monthly depot preparation on Day 1.

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 on Day 1 and at Day 85, or as a 6-monthly depot preparation on Day 1. Participants will also receive 240 milligram (mg) of apalutamide starting at Day 1 as film-coated tablets, to be swallowed whole and together once daily with or without food, for a period of 180 Days.

No Intervention: Observational Cohort(Group3) PSMA-PET Negative Particitpans - 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.


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

Treatment: Drugs: LHRHa
Participants will be administered with LHRHa (example, leuprolide, goserelin, triptorelin acetate) as a 3-monthly depot preparation at Day 1 and Day 85 or as a 6-monthly depot preparation at Day 1.

Treatment: Drugs: Apalutamide
Participants will receive therapeutic dose of apalutamide 240 mg tablets once daily for 180 Days.

Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Prostate specific Membrane Antigen-Positron Emission Tomography (PSMA-PET) Metastatic Progression-free Survival (ppMPFS) - 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.
Timepoint [1] 0 0
Up to 7 years
Secondary outcome [1] 0 0
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 repeated measurement at least 3 Weeks later.
Timepoint [1] 0 0
Up to 7 years
Secondary outcome [2] 0 0
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.
Timepoint [2] 0 0
Up to 7 years
Secondary outcome [3] 0 0
PSA Levels at Week 26 - PSA levels at week 26 will be reported.
Timepoint [3] 0 0
Week 26
Secondary outcome [4] 0 0
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.
Timepoint [4] 0 0
Up to 7 years
Secondary outcome [5] 0 0
Overall Survival - Overall survival is defined as the time from randomization to date of death from any cause.
Timepoint [5] 0 0
Up to 7 years
Secondary outcome [6] 0 0
Prostate Cancer-Specific Survival - Prostate cancer-specific survival is defined as the time from randomization to date of death due to prostate cancer.
Timepoint [6] 0 0
Up to 7 years
Secondary outcome [7] 0 0
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.
Timepoint [7] 0 0
Up to 7 years

Eligibility
Key inclusion criteria
- Histologically confirmed adenocarcinoma of the prostate

- Previously treated with radical prostatectomy with lymph node dissection and first
post-operative prostate-specific antigen (PSA) measurement of less than (<) 0.1
nanogram/milliliter (ng/mL) between Week 6 and Week 13

- 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 or 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 at
diagnosis or time of surgery, OR PSADT less than or equal to (<=) 12 months at the
time of screening using at least 3 consecutive values >=0.1 nanogram per milliliter
(ng/mL), from time of BCR, estimated using the Memorial Sloan Kettering Cancer Center
online calculator

- No evidence of 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 metastatic disease before randomization

- Eastern Cooperative Oncology Group Performance Status Grade 0 or 1
Minimum age
18 Years
Maximum age
No limit
Gender
Males
Can healthy volunteers participate?
No
Key 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

- 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [2] 0 0
Bundaberg Hospital - Bundaberg
Recruitment hospital [3] 0 0
Hervey Bay Hospital - Bundaberg
Recruitment hospital [4] 0 0
Saint Vincent's Hospital - Melbourne - Fitzroy
Recruitment hospital [5] 0 0
Genesis Care Hurstville - Hurstville
Recruitment hospital [6] 0 0
Macquarie University Hospital - North Ryde
Recruitment hospital [7] 0 0
Epworth Healthcare - Richmond
Recruitment hospital [8] 0 0
Calvary Mater Newcastle - Waratah
Recruitment hospital [9] 0 0
GenesisCare Wembley - Wembley
Recruitment postcode(s) [1] 0 0
5042 - Bedford Park
Recruitment postcode(s) [2] 0 0
4670 - Bundaberg
Recruitment postcode(s) [3] 0 0
3065 - Fitzroy
Recruitment postcode(s) [4] 0 0
2220 - Hurstville
Recruitment postcode(s) [5] 0 0
2109 - North Ryde
Recruitment postcode(s) [6] 0 0
3121 - Richmond
Recruitment postcode(s) [7] 0 0
2298 - Waratah
Recruitment postcode(s) [8] 0 0
6014 - Wembley
Recruitment outside Australia
Country [1] 0 0
Austria
State/province [1] 0 0
Innsbruck
Country [2] 0 0
Austria
State/province [2] 0 0
Linz
Country [3] 0 0
Austria
State/province [3] 0 0
Salzburg
Country [4] 0 0
Austria
State/province [4] 0 0
Wien
Country [5] 0 0
Belgium
State/province [5] 0 0
Brugge
Country [6] 0 0
Belgium
State/province [6] 0 0
Gent
Country [7] 0 0
Belgium
State/province [7] 0 0
Kortrijk
Country [8] 0 0
Belgium
State/province [8] 0 0
Wilrijk
Country [9] 0 0
Czechia
State/province [9] 0 0
Plzen
Country [10] 0 0
Czechia
State/province [10] 0 0
Praha 2
Country [11] 0 0
Czechia
State/province [11] 0 0
Praha 5
Country [12] 0 0
Denmark
State/province [12] 0 0
Aalborg
Country [13] 0 0
Denmark
State/province [13] 0 0
Aarhus N.
Country [14] 0 0
Denmark
State/province [14] 0 0
Copenhagen N
Country [15] 0 0
Denmark
State/province [15] 0 0
Herlev
Country [16] 0 0
Germany
State/province [16] 0 0
Dresden
Country [17] 0 0
Germany
State/province [17] 0 0
Essen
Country [18] 0 0
Germany
State/province [18] 0 0
Muenster
Country [19] 0 0
Lebanon
State/province [19] 0 0
Beirut
Country [20] 0 0
Lebanon
State/province [20] 0 0
Jbeil
Country [21] 0 0
Lebanon
State/province [21] 0 0
Zgharta
Country [22] 0 0
Poland
State/province [22] 0 0
Bydgoszcz
Country [23] 0 0
Poland
State/province [23] 0 0
Gdansk
Country [24] 0 0
Poland
State/province [24] 0 0
Gdynia
Country [25] 0 0
Poland
State/province [25] 0 0
Kielce
Country [26] 0 0
Poland
State/province [26] 0 0
Lodz
Country [27] 0 0
Poland
State/province [27] 0 0
Radom
Country [28] 0 0
Poland
State/province [28] 0 0
Warszawa
Country [29] 0 0
Portugal
State/province [29] 0 0
Lisboa
Country [30] 0 0
Portugal
State/province [30] 0 0
Porto
Country [31] 0 0
Russian Federation
State/province [31] 0 0
Ekaterinburg
Country [32] 0 0
Russian Federation
State/province [32] 0 0
Ivanovo
Country [33] 0 0
Russian Federation
State/province [33] 0 0
Moscow
Country [34] 0 0
Russian Federation
State/province [34] 0 0
Nizhni Novgorod
Country [35] 0 0
Russian Federation
State/province [35] 0 0
Omsk
Country [36] 0 0
Russian Federation
State/province [36] 0 0
Pyatigorsk
Country [37] 0 0
Russian Federation
State/province [37] 0 0
Saint Petersburg
Country [38] 0 0
Russian Federation
State/province [38] 0 0
Saint-Petersburg
Country [39] 0 0
Russian Federation
State/province [39] 0 0
Tyumen
Country [40] 0 0
Slovakia
State/province [40] 0 0
Banska Bystrica
Country [41] 0 0
Slovakia
State/province [41] 0 0
Bratislava
Country [42] 0 0
Slovakia
State/province [42] 0 0
Košice
Country [43] 0 0
Slovakia
State/province [43] 0 0
Martin
Country [44] 0 0
Slovakia
State/province [44] 0 0
Nitra
Country [45] 0 0
Slovakia
State/province [45] 0 0
Poprad
Country [46] 0 0
Slovakia
State/province [46] 0 0
Prešov
Country [47] 0 0
Slovakia
State/province [47] 0 0
Trencin
Country [48] 0 0
Spain
State/province [48] 0 0
Málaga
Country [49] 0 0
Spain
State/province [49] 0 0
Navarra
Country [50] 0 0
Spain
State/province [50] 0 0
Pamplona
Country [51] 0 0
Spain
State/province [51] 0 0
Zaragoza
Country [52] 0 0
Sweden
State/province [52] 0 0
Malmö
Country [53] 0 0
Sweden
State/province [53] 0 0
Stockholm
Country [54] 0 0
Turkey
State/province [54] 0 0
Ankara
Country [55] 0 0
Turkey
State/province [55] 0 0
Istanbul
Country [56] 0 0
Turkey
State/province [56] 0 0
Izmir
Country [57] 0 0
Turkey
State/province [57] 0 0
Sakarya

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Janssen-Cilag Ltd.
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT04557059
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Janssen-Cilag Ltd. Clinical Trial
Address 0 0
Janssen-Cilag Ltd.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Study Contact
Address 0 0
Country 0 0
Phone 0 0
844-434-4210
Fax 0 0
Email 0 0
JNJ.CT@sylogent.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04557059