A Randomized Phase 2b Study of ZEN003694 in Combination With Enzalutamide Versus Enzalutamide Monotherapy in Patients With Metastatic Castration-Resistant Prostate Cancer
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 200
- 试验地点
- 47
- 主要终点
- Cohort A: Radiographic progression-free survival (rPFS) by BICR
研究概览
简要总结
This is an open-label, randomized, Phase 2b study of ZEN003694 in combination with enzalutamide vs. enzalutamide monotherapy in patients with mCRPC who have progressed on prior abiraterone by PCWG3 criteria. Disease must have progressed on only abiraterone by PCWG3 criteria prior to study entry.
The patient population will be separated into two cohorts:
Cohort A: Patients with poor response to prior abiraterone defined as:
- Abiraterone started in hormone-sensitive prostate cancer (HSPC) disease setting: < 12 months duration on abiraterone or failure to achieve PSA nadir of 0.2 ng/mL while taking abiraterone, or;
- Abiraterone started in castrate-resistant prostate cancer (CRPC) disease setting: < 6 months duration on abiraterone or failure to achieve PSA50 response while on abiraterone
Cohort B: Patients with response to prior abiraterone, defined as:
- Abiraterone started in hormone-sensitive prostate cancer (HSPC) disease setting: ≥ 12 months duration on abiraterone and nadir PSA < 0.2 ng/mL, or;
- Abiraterone started in castrate-resistant prostate cancer (CRPC) disease setting: ≥ 6 months duration on abiraterone and confirmed PSA50 response
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
- •Males age ≥ 18 years
- •Metastatic, castration-resistant, histologically confirmed prostate cancer
- •Surgical castration or continuous medical castration for ≥ 8 weeks prior to screening; serum testosterone < 50 ng/dL confirmed within 4 weeks of first administration of study drug
- •Have progressed on prior abiraterone treatment by PCWG3 criteria
- •Patients who are not candidates for chemotherapy in the opinion of the investigator or patients who decline chemotherapy
- •Cohort A only - Patient must meet definition of poor responder to abiraterone by one of the following:
- •Abiraterone started in hormone-sensitive prostate cancer (HSPC) disease setting: < 12 months duration on abiraterone or failure to achieve PSA nadir of 0.2 ng/mL while taking abiraterone
- •Abiraterone started in castrate-resistant prostate cancer (CRPC) disease setting: < 6 months duration on abiraterone or failure to achieve a PSA50 response
- •Cohort B only - Patient must meet definition of responder to abiraterone by one of the following:
- •Abiraterone started in hormone-sensitive prostate cancer (HSPC) disease setting: ≥ 12 months duration on abiraterone and nadir PSA < 0.2 ng/mL
- •Abiraterone started in castrate-resistant prostate cancer (CRPC) disease setting: ≥ 6 months duration on abiraterone and PSA50 response
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
排除标准
- •Any history of brain metastases, prior seizure, conditions predisposing to seizure activity
- •Have previously received an investigational BET inhibitor (including previous participation in this study or a study of ZEN003694)
- •Receipt of prior second-generation androgen receptor inhibitors (e.g. enzalutamide, apalutamide, darolutamide, proxalutamide). Receipt of first-generation AR antagonists (e.g. bicalutamide, nilutamide, flutamide) does not count towards this limit.
- •Have received prior chemotherapy in the metastatic castration-resistant setting (prior chemotherapy in the hormone-sensitive setting is allowed provided last dose was at least 6 months prior to first dose of study drug)
- •Have received prior systemic anti-cancer therapy within 2 weeks or five half-lives, whichever is shorter, prior to the first administration of study drug
- •Have received exogenous administration of testosterone therapy since discontinuation of abiraterone.
- •Failure to recover to Grade 1 or lower toxicity related to prior systemic therapy (excluding alopecia and neuropathy) prior to study entry
- •Radiation therapy within 2 weeks of the first administration of study drug
研究组 & 干预措施
Cohort A - ZEN003694 + Enzalutamide
Patients will be administered enzalutamide (160 mg) orally once daily for 21 days prior to the initiation of the combination therapy (Lead-in) to reach steady state concentration (Css) prior to Cycle 1. After the Lead-in, ZEN003694 (72 mg) will be administered orally one daily in combination with daily enzalutamide for 28-day cycles.
干预措施: ZEN003694 (Drug)
Cohort B - ZEN003694 + Enzalutamide
Patients will be administered enzalutamide (160 mg) orally once daily for 21 days prior to the initiation of the combination therapy (Lead-in) to reach steady state concentration (Css) prior to Cycle 1. After the Lead-in, ZEN003694 (72 mg) will be administered orally one daily in combination with daily enzalutamide for 28-day cycles.
干预措施: ZEN003694 (Drug)
Cohort A - ZEN003694 + Enzalutamide
Patients will be administered enzalutamide (160 mg) orally once daily for 21 days prior to the initiation of the combination therapy (Lead-in) to reach steady state concentration (Css) prior to Cycle 1. After the Lead-in, ZEN003694 (72 mg) will be administered orally one daily in combination with daily enzalutamide for 28-day cycles.
干预措施: Enzalutamide (Drug)
Cohort A - Enzalutamide
Patients will be administered enzalutamide (160 mg) orally once daily for 21 days prior to Cycle 1 Day 1 (Lead-in). After the Lead-in, patients will be administered enzalutamide 160 mg orally once daily for 28-day cycles. Active control patients will have the option to cross-over to treatment with ZEN003694 in combination with enzalutamide upon confirmed radiographic progression by PCWG3 criteria by independent central review.
干预措施: Enzalutamide (Drug)
Cohort B - ZEN003694 + Enzalutamide
Patients will be administered enzalutamide (160 mg) orally once daily for 21 days prior to the initiation of the combination therapy (Lead-in) to reach steady state concentration (Css) prior to Cycle 1. After the Lead-in, ZEN003694 (72 mg) will be administered orally one daily in combination with daily enzalutamide for 28-day cycles.
干预措施: Enzalutamide (Drug)
Cohort B - Enzalutamide
Patients will be administered enzalutamide (160 mg) orally once daily for 21 days prior to Cycle 1 Day 1 (Lead-in). After the Lead-in, patients will be administered enzalutamide 160 mg orally once daily for 28-day cycles. Active control patients will have the option to cross-over to treatment with ZEN003694 in combination with enzalutamide upon confirmed radiographic progression by PCWG3 criteria by independent central review.
干预措施: Enzalutamide (Drug)
结局指标
主要结局
Cohort A: Radiographic progression-free survival (rPFS) by BICR
时间窗: Randomization up to 30 months
Time from date of randomization to the date of first disease radiographic progression or death for any reason. Radiographic progression disease will be evaluated by RECIST 1.1 and PCWG3.
次要结局
- Cohort A: Assess efficacy endpoints for patients enrolled in the USA(Randomization up to 30 months)
- Cohort A + B: PSA50 response rate(Randomization up to 30 months)
- Cohorts A + B: Radiographic progression-free survival (rPFS) by BICR(Randomization up to 30 months)
- Cohort A: Radiographic progression-free survival (rPFS) by investigator assessment(Randomization up to 30 months)
- Cohort A + B: Radiographic progression-free survival (rPFS) by investigator assessment(Randomization up to 30 months)
- Cohort A: Progression-free survival (PFS) by investigator assessment(Randomization up to 30 months)
- Cohort A + B: Progression-free survival (PFS) by investigator assessment(Randomization up to 30 months)
- Cohort A: Overall survival (OS)(Randomization up to 30 months)
- Cohort A + B: Overall survival (OS)(Randomization up to 30 months)
- Cohort A: PSA50 response rate(Randomization up to 30 months)
- Cohort A + B: Assess efficacy endpoints for patients enrolled in the USA(Randomization up to 30 months)
- Objective response rate (ORR)(Randomization up to 30 months)
- Patient-reported health status and quality of life (QoL) measured by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)(Screening and Day 1 of every 28-day Cycle up to 30 months)
- Patient-reported health status and quality of life (QoL) measured by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Prostate Module (EORTC QLQ-PR25).(Screening and Day 1 of every 28-day Cycle up to 30 months)
- Time to initiation of chemotherapy(Randomization up to 30 months)
- Time to first skeletal related event (SRE)(Randomization up to 30 months)
- Measure plasma concentrations of ZEN003694 and the active metabolite ZEN003791(Cycle 1 Day 1: Pre-dose, 1 hour, 2 hours, and 4 hours post-dose; Cycle 2 Day1: Pre-dose, 1 hour, 2 hours, and 4 hours post-dose)