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 (PRIMORDIUM)

• ClinicalTrials.gov Identifier: NCT04557059
• Recruitment Status: Recruiting
• First Posted: September 21, 2020
• Last Update Posted: May 6, 2023
• Sponsor: Janssen Pharmaceutica N.V., Belgium
• Information provided by (Responsible Party): Janssen Pharmaceutica N.V., Belgium

Tracking Information

• First Submitted Date: September 17, 2020
• First Posted Date: September 21, 2020
• Last Update Posted Date: May 6, 2023
• Actual Study Start Date: November 12, 2020
• Estimated Primary Completion Date: January 14, 2028 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 17, 2020)

Prostate specific Membrane Antigen-Positron Emission Tomography (PSMA-PET) Metastatic Progression-free Survival (ppMPFS) [ Time Frame: 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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 17, 2020)

• Time to Prostate-Specific Antigen (PSA) Progression [ Time Frame: 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.
• PSA Response Rate [ Time Frame: 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.
• PSA Levels at Week 26 [ Time Frame: Week 26 ]
  PSA levels at week 26 will be reported.
• Time to Loco-Regional Progression by PSMA-PET [ Time Frame: 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.
• Overall Survival [ Time Frame: Up to 7 years ]
  Overall survival is defined as the time from randomization to date of death from any cause.
• Prostate Cancer-Specific Survival [ Time Frame: Up to 7 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) [ Time Frame: 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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief 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
• 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
• 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: 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 Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: 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.
• Drug: Apalutamide
  Participants will receive therapeutic dose of apalutamide 240 mg once daily for 180 Days.
  Other Name: JNJ-56021927

Study Arms

• 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.
  Interventions:

  • Radiation: Radiotherapy
  • Drug: LHRHa
• 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.
  Interventions:

  • Radiation: Radiotherapy
  • Drug: LHRHa
  • Drug: Apalutamide
• 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.

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: September 17, 2020): 412
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: January 28, 2030
• Estimated Primary Completion Date: January 14, 2028 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Study Contact; 844-434-4210; Participate-In-This-Study@its.jnj.com

• Listed Location Countries: Australia, Austria, Belgium, Brazil, Czechia, Denmark, Finland, Hungary, Italy, Jordan, Lebanon, Mexico, Poland, Portugal, Russian Federation, Slovakia, Spain, Sweden, Turkey, United States
• Removed Location Countries: Germany, United Kingdom

Administrative Information

• NCT Number: NCT04557059
• Other Study ID Numbers: CR108705; 56021927PCR3015 ( Other Identifier: Janssen Pharmaceutica N.V., Belgium ); 2019-002957-46 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu
• URL: https://www.janssen.com/clinical-trials/transparency

• Current Responsible Party: Janssen Pharmaceutica N.V., Belgium
• Original Responsible Party: Janssen-Cilag Ltd.
• Current Study Sponsor: Janssen Pharmaceutica N.V., Belgium
• Original Study Sponsor: Janssen-Cilag Ltd.
• Collaborators: Not Provided

Investigators

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

• PRS Account: Janssen Pharmaceutica N.V., Belgium
• Verification Date: May 2023