A Study of Adding Apalutamide to Radiotherapy and LHRH Ag... | NCT04557059

NCT04557059

ID	Type	Description
56021927PCR3015	Other Identifier	Janssen Research & Development, LLC
2019-002957-46	EudraCT Number
2023-505852-23-00	Registry Identifier	EUCT number

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Interventional Cohort (Group 1): RT+ LHRHa	Active Comparator	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.	Radiation: Radiotherapy Drug: LHRHa
Interventional Cohort (Group 2): RT+LHRHa + Apalutamide	Experimental	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.	Radiation: Radiotherapy Drug: LHRHa Drug: Apalutamide
Observational Cohort(Group3) PSMA-PET Negative Participants	No Intervention	Enrollment into this cohort will be stopped further. Participants who were PSMA-PET-negative at screening and were already enrolled in the Observational Cohort will continue in this 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. The use of any medicinal product(s) for the treatment and management of participants will be at discretion of the treating physician.

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Radiotherapy	Radiation	Participants will receive radiotherapy (RT) with or without optional stereotactic body radiation therapy (SBRT), which will start within 4 weeks after randomization.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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 Outcomes

Measure	Description	Time Frame
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

Eligibility Module

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

Facility	Status	City	State	ZIP	Country	Contacts
Arizona Urology Specialists		Tucson	Arizona	85741	United States
Arkansas Urology

ID	Term
D005834	Genital Neoplasms, Male
D014565	Urogenital Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D005832	Genital Diseases, Male
D000091662	Genital Diseases
D000091642	Urogenital Diseases
D011469	Prostatic Diseases
D052801	Male Urogenital Diseases