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 Hormone-Sensitive Prostate Cancer, Assessed by PSMA-PET With an Observational Cohort
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 691
- 试验地点
- 141
- 主要终点
- Prostate specific Membrane Antigen-Positron Emission Tomography (PSMA-PET) Metastatic Progression-free Survival (ppMPFS)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Interventional Cohort (Group 1): RT+ LHRHa
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.
干预措施: Radiotherapy (Radiation)
Interventional Cohort (Group 2): RT+LHRHa + Apalutamide
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.
干预措施: Apalutamide (Drug)
Interventional Cohort (Group 2): RT+LHRHa + Apalutamide
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.
干预措施: LHRHa (Drug)
Observational Cohort(Group3) PSMA-PET Negative Participants
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.
Interventional Cohort (Group 1): RT+ LHRHa
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.
干预措施: LHRHa (Drug)
Interventional Cohort (Group 2): RT+LHRHa + Apalutamide
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.
干预措施: Radiotherapy (Radiation)
结局指标
主要结局
Prostate specific Membrane Antigen-Positron Emission Tomography (PSMA-PET) Metastatic Progression-free Survival (ppMPFS)
时间窗: Up to 9 years
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.
次要结局
- PSA Response Rate(Up to 9 years)
- PSA Levels at Week 26(Week 26)
- Prostate Cancer-Specific Survival(Up to 9 years)
- Number of Participants With Adverse Event (AE) and Serious Adverse Events (SAEs)(Up to 9 years)
- Overall Survival(Up to 9 years)
- Time to Prostate-Specific Antigen (PSA) Progression(Up to 9 years)
- Time to Loco-Regional Progression by PSMA-PET(Up to 9 years)