HERO: A Multinational Phase 3 Randomized, Open-label, Parallel Group Study to Evaluate the Safety and Efficacy of Relugolix in Men With Advanced Prostate Cancer
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,134
- 试验地点
- 149
- 主要终点
- Sustained Castration Rate
研究概览
简要总结
The purpose of this study is to determine the efficacy and safety of relugolix 120 milligrams (mg) orally once daily for 48 weeks on maintaining serum testosterone suppression to castrate levels (< 50 nanograms/deciliter [ng/dL]) in participants with androgen-sensitive advanced prostate cancer.
详细描述
This is a phase 3, multinational, randomized, open-label, parallel group study to evaluate the efficacy and safety of oral daily relugolix 120 mg in participants with androgen-sensitive advanced prostate cancer who require at least 1 year of continuous androgen-deprivation therapy. Relugolix 120 mg orally once daily or leuprolide acetate depot suspension, 22.5 mg (or 11.25 mg in Japan and Taiwan based on local labels), every 3 months by subcutaneous injection will be administered to participants.
There are 2 analyses for this study, a primary analysis and a final analysis.
Primary Analysis:
The primary analysis of efficacy and safety has been completed (N=934). Participants were randomized 2:1 to receive relugolix or leuprolide for 48 weeks, followed by a 30-day safety follow-up visit or early termination 30-day safety follow-up.
Final Analysis:
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
- •Has histologically or cytologically confirmed diagnosis of adenocarcinoma of the prostate.
- •Is a candidate for, in the opinion of the investigator, at least 1 year of continuous androgen deprivation therapy for the management of androgen-sensitive advanced prostate cancer with 1 of the following clinical disease state presentations:
- •Evidence of biochemical (PSA) or clinical relapse following local primary intervention with curative intent, such as surgery, radiation therapy, cryotherapy, or high-frequency ultrasound and not a candidate for salvage treatment by surgery; or
- •Newly diagnosed androgen-sensitive metastatic disease; or
- •Advanced localized disease unlikely to be cured by local primary intervention with either surgery or radiation with curative intent.
- •Has a serum testosterone at the Screening visit of ≥ 150 ng/dL (5.2 nanomoles [nmol]/liter [L]).
- •Has a serum PSA concentration at the Screening visit of > 2.0 ng/milliliter (mL) (2.0 microgram [μg]/L), or, when applicable, post radical prostatectomy of > 0.2 ng/mL (0.2 μg/L) or post radiotherapy, cryotherapy, or high frequency ultrasound > 2.0 ng/mL (2.0 μg/L) above the post interventional nadir.
- •Has an Eastern Cooperative Oncology Group performance status of 0 or 1 at initial screening and at baseline.
排除标准
- •In the investigator's opinion, is likely to require chemotherapy or surgical therapy for symptomatic disease management within 2 months of initiating androgen deprivation therapy.
- •Previously received gonadotropin-releasing hormone analog or other form of androgen deprivation therapy (estrogen or antiandrogen) for > 18 months total duration. If androgen deprivation therapy was received for ≤ 18 months total duration, then that therapy must have been completed at least 3 months prior to baseline. If the dosing interval of the depot is longer than 3 months, then the prior androgen deprivation therapy must have been completed at least as long as the dosing interval of the depot.
- •Previous systemic cytotoxic treatment for prostate cancer (for example, taxane-based regimen).
- •Metastases to brain per prior clinical evaluation.
- •Participants with myocardial infarction, unstable symptomatic ischemic heart disease, cerebrovascular events, or any significant cardiac condition within the prior 6 months.
- •Active conduction system abnormalities.
- •Uncontrolled hypertension.
研究组 & 干预措施
Relugolix
Relugolix for 48 weeks
干预措施: Relugolix (Drug)
Leuprolide Acetate
Leuprolide acetate for 48 weeks
干预措施: Leuprolide Acetate (Drug)
结局指标
主要结局
Sustained Castration Rate
时间窗: From Week 5 Day 1 (Day 29) to Week 49 Day 1 (Day 337)
Sustained castration rate defined as the cumulative probability of testosterone suppression to \< 50 nanogram (ng)/deciliter (dL). The rate was estimated for each treatment group using the Kaplan-Meier method and reported as percentage of participants. The lower bound of the 95% confidence interval (CI) for the cumulative probability of sustained testosterone suppression in the relugolix treatment group must have been ≥ 90% to meet evaluation criteria for efficacy.
次要结局
- Change From Baseline In QoL Total Score As Assessed By The EORTC-QLQ-PR25 Sexual Activity And Functioning And Hormonal-Treatment-Related Symptom Subdomains(Baseline, Week 49 Day 1 (Day 337))
- Change From Baseline In QoL Total Score As Assessed By The European Quality Of Life 5-Dimension 5-Level Questionnaire (EuroQoL EQ-5D-5L)(Baseline, Week 49 Day 1 (Day 337))
- Percent Change From Baseline In Serum Concentrations Of FSH(Week 1 Day 4 (Day 4), Week 5 Day 1 (Day 29), Week 25 Day 1 (Day 169), and Week 49 Day 1 (Day 337))
- Percent Change From Baseline In Serum Concentrations Of Sex Hormone-Binding Globulin(Week 5 Day 1 (Day 29), Week 25 Day 1 (Day 169), and Week 49 Day 1 (Day 337))
- Maximum Observed Plasma Concentration (Cmax) Of Relugolix(Predose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hours postdose on Day 1 and Week 2)
- Profound Castration Rate At Week 3 Day 1 (Day 15)(Week 3 Day 1 (Day 15))
- PSA Response Rate At Week 3 Day 1(Week 3 Day 1 (Day 15))
- PSA Response Rate At Week 5 Day 1(Week 5 Day 1 (Day 29))
- Testosterone Recovery Rate(Day 90 follow-up)
- Sustained Profound Castration Rate From Week 5 Day 1 Through Week 49 Day 1(Week 5 Day 1 (Day 29) through Week 49 Day 1 (Day 337))
- Undetectable PSA Rate(Week 25 Day 1 (Day 169))
- Rate Of PSA Progression-free Survival(Week 49 Day 1 (Day 337))
- Percent Change From Baseline In Serum Concentrations Of Luteinizing Hormone(Week 1 Day 4 (Day 4), Week 5 Day 1 (Day 29), Week 25 Day 1 (Day 169), and Week 49 Day 1 (Day 337))
- Area Under The Concentration-Time Curve (AUC0-τ) Of Relugolix(Predose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hours postdose on Day 1 and Week 2)
- Castration Rate At Week 1 Day 4(Week 1 Day 4 (Day 4))
- Confirmed Prostate-specific Antigen (PSA) Response Rate(Week 3 Day 1 (Day 15) and Week 5 Day 1 (Day 29))
- Castration Rate At Week 3 Day 1(Week 3 Day 1 (Day 15))
- Follicle-stimulating Hormone (FSH) Level(Week 25 Day 1 (Day 169))
- Profound Castration Rate At Week 1 Day 4 (Day 4)(At Week 1 Day 4 (Day 4))
- Change From Baseline In Quality Of Life (QoL) Total Score As Assessed By The Global Health Domain Of The European Organisation Of Research And Treatment Of Cancer (EORTC)-Quality Of Life Questionnaire (QLQ)-C30(Baseline, Week 49 Day 1 (Day 337))
- Change From Baseline In QoL Total Score For Remaining Domain Scores As Assessed By The EORTC-QLQ-C30(Baseline, Week 49 Day 1 (Day 337))
- Change From Baseline In QoL Total Score For Urinary And Bowel Symptoms Domains As Assessed By The EORTC-QLQ-PR25(Baseline, Week 49 Day 1 (Day 337))
- Time To Maximum Observed Plasma Concentration (Tmax) Of Relugolix(Predose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hours postdose on Day 1 and Week 2)
- Sustained Profound Castration Rate From Week 25 Day 1 Through Week 49 Day 1(Week 25 Day 1 (Day 169) through Week 49 Day 1 (Day 337))
- Percent Change From Baseline In Serum Concentrations Of Dihydrotestosterone(Week 5 Day 1 (Day 29), Week 25 Day 1 (Day 169), and Week 49 Day 1 (Day 337))