A Randomized, Double-blind, Placebo-controlled Phase 3 Study of Darolutamide in Addition to Androgen Deprivation Therapy (ADT) Versus Placebo Plus ADT in Men With Metastatic Hormone-sensitive Prostate Cancer (mHSPC)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 669
- 试验地点
- 167
- 主要终点
- Radiological Progression-free Survival (rPFS) Assessed by Central Review
研究概览
简要总结
The purpose of the study is to assess the efficacy and safety of darolutamide in combination with standard androgen deprivation therapy (ADT) in patients with metastatic hormone sensitive prostate cancer.
研究设计
- 研究类型
- 干预性
- 分配方式
- 随机
- 干预模型
- 平行分组
- 主要目的
- 治疗
- 盲法
- 四盲 (受试者、医护人员、研究者、结局评估者)
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 or cytologically confirmed adenocarcinoma of prostate
- Metastatic disease
- Started ADT (LHRH agonist/antagonist or orchiectomy) with or without first generation anti-androgen, but not earlier than 12 weeks before randomization
- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0, 1 or 2
- Adequate bone marrow, liver and renal function
排除标准
- Prior treatment with: LHRH agonist/antagonists except neoadjuvant and /or adjuvant therapy; Second-generation androgen receptor (AR) inhibitors such as enzalutamide, darolutamide, apalutamide or other investigational AR inhibitors; Cytochrome P17 enzyme inhibitor such as abiraterone acetate or oral ketoconazole as anti-cancer treatment for prostate cancer; Chemotherapy including docetaxel or immunotherapy for prostate cancer; Use of systemic corticosteroid with dose greater than the equivalent 10 mg of prednisone/day within 28 days prior to randomization; Radiopharmaceuticals; Any other anti-cancer treatment for prostate cancer, excluding local therapies and ADT.
- Treatment with radiotherapy within 2 weeks before randomization
- Contraindication to iodinated CT and gadolinium chelate MRI intravenous contrast agent(s)
- Had any of the following within 6 months before randomization: stroke, myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, congestive heart failure (New York Heart Association Class III or IV)
- Uncontrolled hypertension as indicated by a resting systolic BP ≥ 160 mmHg or diastolic BP ≥ 100 mmHg despite medical management
- A gastrointestinal (GI) disorder or procedure which is expected to interfere significantly with absorption of study drug
- Any prior malignancy (other than adequately treated basal cell or squamous cell skin cancer, superficial bladder cancer, or any other cancer in situ currently in complete remission) within 5 years prior to randomization
- Inability to swallow oral medications
研究组 & 干预措施
Placebo+ADT
Participants will receive placebo twice daily with food and ADT of investigator's choice as standard therapy
干预措施: Placebo (Drug)
Placebo+ADT
Participants will receive placebo twice daily with food and ADT of investigator's choice as standard therapy
干预措施: Androgen deprivation therapy (ADT) (Other)
Darolutamide+ADT
Participants will receive darolutamide 600 mg (2 tablets of 300 mg) twice daily with food and ADT of investigator's choice as standard therapy
干预措施: Darolutamide (Nubeqa, BAY1841788) (Drug)
Darolutamide+ADT
Participants will receive darolutamide 600 mg (2 tablets of 300 mg) twice daily with food and ADT of investigator's choice as standard therapy
干预措施: Androgen deprivation therapy (ADT) (Other)
方案终点
主要结局
Radiological Progression-free Survival (rPFS) Assessed by Central Review
时间窗: From randomization to the date when 222 rPFS events were observed, approximately 36 months
rPFS used conventional imaging method (99mTc-phosphonate bone scan, CT/MRI scan). rPFS was defined as the time from the date of randomization to the date of progressive disease in malignant soft tissue lesions, progressive disease in malignant bone lesions, or death due to any cause, whichever occurs first. Malignant soft tissue lesions were assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria and malignant bone lesions were assessed by Prostate Cancer Clinical Trials Working Group (PCWG3) criteria.
次要结局
- Overall Survival (OS)(From randomization to the final analysis date, approximately 47 months)
- Time to Initiation of Subsequent Anti-cancer Therapy(From randomization to the date when 222 rPFS events were observed, approximately 36 months)
- Overall Survival (OS)(From randomization to the date when 222 rPFS events were observed, approximately 36 months)
- Time to Castration-Resistant Prostate Cancer (CRPC)(From randomization to the date when 222 rPFS events were observed, approximately 36 months)
- Time to PSA Progression(From randomization to the date when 222 rPFS events were observed, approximately 36 months)
- PSA Undetectable Rates (<0.2 ng/mL)(From randomization to the date when 222 rPFS events were observed, approximately 36 months)
- Time to Pain Progression(From randomization to the date when 222 rPFS events were observed, approximately 36 months)
- Number of Participants With Adverse Events as a Measure of Safety(From start of study drug administration until 30 days after the last administration)
试验结果
结果已于 2025-08-08 在 ClinicalTrials.gov 公示。 在 ClinicalTrials.gov 查看
受试者流程
入组 669 人 · 完成 291 人
主要终点
Radiological Progression-free Survival (rPFS) Assessed by Central Review
Months · 95% Confidence Interval · 时间窗: From randomization to the date when 222 rPFS events were observed, approximately 36 months
| Darolutamide+ADT （n=446） | Placebo+ADT （n=223） |
|---|---|
| NA (NA–NA) | 25.0 (19.0–NA) |
Full analysis set (FAS)
Darolutamide+ADT: NA signifies that value cannot be estimated due to insufficient number of participants with events.
Placebo+ADT: NA signifies that value cannot be estimated due to insufficient number of participants with events.
Hazard Ratio (HR) 0.541 · 95% 置信区间 0.413–0.707 · p = <0.0001 · Log Rank
One-sided
其他终点（7）
Overall Survival (OS)
Months · 95% Confidence Interval · 时间窗: From randomization to the final analysis date, approximately 47 months
| 分类 | Darolutamide+ADT （n=446） | Placebo+ADT （n=223） |
|---|---|---|
| At primary completion cut-off | NA (NA–NA) | NA (33.8–NA) |
| At final analysis cut-off | NA (NA–NA) | NA (NA–NA) |
Full Analysis Set (FAS)
Darolutamide+ADT: NA signifies that value cannot be estimated due to insufficient number of participants with events.
Placebo+ADT: NA signifies that value cannot be estimated due to insufficient number of participants with events.
Darolutamide+ADT: NA signifies that value cannot be estimated due to insufficient number of participants with events.
Placebo+ADT: NA signifies that value cannot be estimated due to insufficient number of participants with events.
Hazard Ratio (HR) 0.813 · 95% 置信区间 0.591–1.118 · p = 0.1007 · Log Rank
One-sided
Hazard Ratio (HR) 0.776 · 95% 置信区间 0.577–1.045 · p = 0.0473 · Log Rank
One-sided
Time to Castration-Resistant Prostate Cancer (CRPC)
Months · 95% Confidence Interval · 时间窗: From randomization to the date when 222 rPFS events were observed, approximately 36 months
| Darolutamide+ADT （n=446） | Placebo+ADT （n=223） |
|---|---|
| NA (NA–NA) | 13.8 (12.0–16.8) |
Full Analysis Set (FAS)
Darolutamide+ADT: NA signifies that value cannot be estimated due to insufficient number of participants with events.
Hazard Ratio (HR) 0.404 · 95% 置信区间 0.321–0.508
Time to Initiation of Subsequent Anti-cancer Therapy
Months · 95% Confidence Interval · 时间窗: From randomization to the date when 222 rPFS events were observed, approximately 36 months
| Darolutamide+ADT （n=446） | Placebo+ADT （n=223） |
|---|---|
| NA (NA–NA) | NA (27.7–NA) |
Full Analysis Set (FAS)
Darolutamide+ADT: NA signifies that value cannot be estimated due to insufficient number of participants with events.
Placebo+ADT: NA signifies that value cannot be estimated due to insufficient number of participants with events.
Hazard Ratio (HR) 0.401 · 95% 置信区间 0.288–0.558
Time to PSA Progression
Months · 95% Confidence Interval · 时间窗: From randomization to the date when 222 rPFS events were observed, approximately 36 months
| Darolutamide+ADT （n=446） | Placebo+ADT （n=223） |
|---|---|
| NA (NA–NA) | 16.8 (13.9–20.1) |
Full Analysis Set (FAS)
Darolutamide+ADT: NA signifies that value cannot be estimated due to insufficient number of participants with events.
Hazard Ratio (HR) 0.306 · 95% 置信区间 0.231–0.405
PSA Undetectable Rates (<0.2 ng/mL)
Percentage of participants · 95% Confidence Interval · 时间窗: From randomization to the date when 222 rPFS events were observed, approximately 36 months
| Darolutamide+ADT （n=425） | Placebo+ADT （n=211） |
|---|---|
| 62.6 (57.8–67.2) | 18.5 (13.5–24.4) |
Participants with detectable PSA values ≥0.2 ng/mL at baseline
Rate difference 44.3 · 95% 置信区间 37.4–51.2
Time to Pain Progression
Months · 95% Confidence Interval · 时间窗: From randomization to the date when 222 rPFS events were observed, approximately 36 months
| Darolutamide+ADT （n=446） | Placebo+ADT （n=223） |
|---|---|
| NA (NA–NA) | 29.9 (29.7–NA) |
Full Analysis Set (FAS)
Darolutamide+ADT: NA signifies that value cannot be estimated due to insufficient number of participants with events.
Placebo+ADT: NA signifies that value cannot be estimated due to insufficient number of participants with events.
Hazard Ratio (HR) 0.721 · 95% 置信区间 0.544–0.957
Number of Participants With Adverse Events as a Measure of Safety
Participants · 时间窗: From start of study drug administration until 30 days after the last administration
| 分类 | Darolutamide (DB) （n=446） | Darolutamide (DB + OL) （n=446） | Placebo (DB) （n=220） | Placebo - Darolutamide (CO) （n=59） |
|---|---|---|---|---|
| Any TEAE | 407 | 409 | 199 | 30 |
| Any TESAE | 109 | 126 | 52 | 8 |
| Any study drug-related TEAE | 147 | 154 | 64 | 8 |
Safety analysis set (SAF)
安全性
| 组别 | 严重不良事件 | 死亡 |
|---|---|---|
| Darolutamide (DB) | 109 / 446 | 123 / 446 |
| Darolutamide (DB + OL) | 126 / 446 | 126 / 446 |
| Placebo (DB) | 52 / 220 | 76 / 220 |
| Placebo - Darolutamide (CO) | 8 / 59 | 2 / 59 |
最常见的严重不良事件（人数）
| 事件 | Darolutamide (DB) | Darolutamide (DB + OL) | Placebo (DB) | Placebo - Darolutamide (CO) |
|---|---|---|---|---|
| Urinary tract infection | 8 / 446 | 8 / 446 | 1 / 220 | 0 / 59 |
| Pneumonia | 6 / 446 | 7 / 446 | 2 / 220 | 0 / 59 |
| Spinal cord compression | 5 / 446 | 5 / 446 | 0 / 220 | 0 / 59 |
| Anaemia | 4 / 446 | 4 / 446 | 3 / 220 | 0 / 59 |
| Atrial fibrillation | 3 / 446 | 4 / 446 | 0 / 220 | 0 / 59 |
| Bone pain | 4 / 446 | 4 / 446 | 1 / 220 | 0 / 59 |
| Angina pectoris | 3 / 446 | 3 / 446 | 0 / 220 | 0 / 59 |
| Angina unstable | 2 / 446 | 3 / 446 | 0 / 220 | 0 / 59 |
| Myocardial infarction | 3 / 446 | 3 / 446 | 0 / 220 | 1 / 59 |
| Death | 2 / 446 | 3 / 446 | 2 / 220 | 0 / 59 |
数值为申办方在 ClinicalTrials.gov 公示的原始数据，未经重新计算；括号内为公示的离散度（如 95% 置信区间）。
相关文献
- 相关文献（PubMed 关联）Saad F, Shore N, Vjaters E, Olmos D, Littleton N, Testa I, Mo M, Verholen F, Srinivasan S, Haresh KP. Darolutamide Plus Androgen-deprivation Therapy in Metastatic Hormone-sensitive Prostate Cancer by Disease Volume and Risk Subgroups in the Phase 3 ARANOTE Trial. Eur Urol. 2026 Aug 12:S0302-2838(26)02313-4. doi: 10.1016/j.eururo.2026.07.026. Online ahead of print. PubMed 42586872
- 相关文献（PubMed 关联）Morgans AK, Haresh KP, Jievaltas M, Olmos D, Shore ND, Vjaters E, Xing N, Mohamed AF, Littleton N, Srinivasan S, Verholen F, Saad F. Pain and health-related quality-of-life outcomes with darolutamide in metastatic hormone-sensitive prostate cancer (ARANOTE): secondary and exploratory analyses of a multicentre, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2026 May;27(5):614-624. doi: 10.1016/S1470-2045(26)00014-8. Epub 2026 Apr 9. PubMed 41969015
- 相关文献（PubMed 关联）Saad F, Vjaters E, Shore N, Olmos D, Xing N, Pereira de Santana Gomes AJ, Cesar de Andrade Mota A, Salman P, Jievaltas M, Ulys A, Jakubovskis M, Kopyltsov E, Han W, Nevalaita L, Testa I, Le Berre MA, Kuss I, Haresh KP; ARANOTE Study Investigators. Darolutamide in Combination With Androgen-Deprivation Therapy in Patients With Metastatic Hormone-Sensitive Prostate Cancer From the Phase III ARANOTE Trial. J Clin Oncol. 2024 Dec 20;42(36):4271-4281. doi: 10.1200/JCO-24-01798. Epub 2024 Sep 16. PubMed 39279580
研究者
研究点 (167)
标识符
- NCT 编号
- NCT04736199
- 其他研究编号
- 21140, 2022-502244-12-00, 2020-003093-48
日期
- 首次提交
- (5年前)
- 首次发布
- (5年前)
- 主要完成日期
- (2年前)
- 研究完成日期
- (8个月前)
- 最近核实
- (29天前)
- 最近更新
- (昨天)
监管与共享
- FDA 监管药物
- 是
- FDA 监管器械
- 否
- 个体参与者数据共享计划
- 否
- 是否有结果
- 是
Availability of this study's data will be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014. Interested researchers can use www.clinicalstudydatarequest.com to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the Study sponsors section of the portal.
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