Description:
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.
Title
- 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
Clinical Trial IDs
- ORG STUDY ID:
CR108705
- SECONDARY ID:
56021927PCR3015
- SECONDARY ID:
2019-002957-46
- NCT ID:
NCT04557059
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| LHRHa | | Interventional Cohort (Group 1): RT+ LHRHa |
| Apalutamide | JNJ-56021927 | Interventional Cohort (Group 2): RT+LHRHa + Apalutamide |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Interventional Cohort (Group 1): RT+ LHRHa | Active Comparator | 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. | |
| Interventional Cohort (Group 2): RT+LHRHa + Apalutamide | Experimental | 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. | |
| Observational Cohort(Group3) PSMA-PET Negative Particitpans | No Intervention | 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. | |
Eligibility Criteria
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
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
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | Male |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Prostate specific Membrane Antigen-Positron Emission Tomography (PSMA-PET) Metastatic Progression-free Survival (ppMPFS) |
| Time Frame: | Up to 7 years |
| Safety Issue: | |
| Description: | 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
| Measure: | Time to Prostate-Specific Antigen (PSA) Progression |
| Time Frame: | Up to 7 years |
| Safety Issue: | |
| Description: | 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. |
| Measure: | PSA Response Rate |
| Time Frame: | Up to 7 years |
| Safety Issue: | |
| Description: | PSA response rate is defined as the percentage of participants with a PSA decrease of >= 50 percent (%), >= 90% or undetectable from baseline. |
| Measure: | PSA Levels at Week 26 |
| Time Frame: | Week 26 |
| Safety Issue: | |
| Description: | PSA levels at week 26 will be reported. |
| Measure: | Time to Loco-Regional Progression by PSMA-PET |
| Time Frame: | Up to 7 years |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Overall Survival |
| Time Frame: | Up to 7 years |
| Safety Issue: | |
| Description: | Overall survival is defined as the time from randomization to date of death from any cause. |
| Measure: | Prostate Cancer-Specific Survival |
| Time Frame: | Up to 7 years |
| Safety Issue: | |
| Description: | Prostate cancer-specific survival is defined as the time from randomization to date of death due to prostate cancer. |
| Measure: | Number of Participants With Adverse Event (AE) and Serious Adverse Events (SAEs) |
| Time Frame: | Up to 7 years |
| Safety Issue: | |
| Description: | 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. |
Details
| Phase: | Phase 3 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Janssen Pharmaceutica N.V., Belgium |
Last Updated
August 20, 2021
