A Randomized, 2-cohort, Double-blind, Placebo-controlled, Phase III Study of Saruparib (AZD5305) in Combination With Physician's Choice New Hormonal Agents in Patients With HRRm and Non-HRRm Metastatic Castration-Sensitive Prostate Cancer (EvoPAR-Prostate01)
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- AstraZeneca
- 入组人数
- 1,898
- 试验地点
- 324
- 主要终点
- Radiographic Progression-Free Survival (rPFS)
研究概览
简要总结
The intention of the study is to demonstrate superiority of Saruparib (AZD5305) + physician's choice NHA relative to placebo + physician's choice NHA by assessment of radiographic progression-free survival (rPFS) in participants with mCSPC.
详细描述
Approximately 1800 adult participants with mCSPC will be assigned to one of two cohorts (550 HRRm and 1250 non-HRRm) and randomized in a 1:1 ratio to receive either Saruparib (AZD5305) with NHA or placebo with NHA. They will receive their assigned treatment and regular tumor evaluation scans until disease progression, or until treatment is stopped for another reason.
All patients will be followed for survival until the end of the study. Independent data monitoring committee (DMC) composed of independent experts will be convened to confirm the safety and tolerability of Saruparib (AZD5305) + physicians choice NHA.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Double-blind
入排标准
- 年龄范围
- 18 Years 至 130 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Male ≥ 18 years of age.
- •Histologically documented prostate adenocarcinoma which is de novo or recurrent and castration-sensitive. Participants with pathologic features of small cell, neuroendocrine, sarcomatoid, spindle cell, or signet cell histology are not eligible.
- •Metastatic disease as documented by the investigator prior to randomisation, with clear evidence of ≥ 1 bone lesion and/or ≥ 1 soft tissue lesion that is suitable for repeated assessment with CT and/or MRI.
- •Participant is receiving ADT with a GnRH analogue or has undergone bilateral orchiectomy starting ≥ 14 days and < 4 months prior to randomisation.
- •ECOG performance status of 0 or 1 with no deterioration over the 2 weeks prior to randomisation.
- •Provision of FFPE tumour tissue sample and blood sample (for ctDNA).
- •Confirmed HRRm status by central tumour tissue and/or ctDNA test is required to determine cohort eligibility.
- •Adequate organ and bone marrow function as described in study protocol.
- •Participants must not father children or donate sperm from signing ICF, during the study intervention and for 6 months after the last dose of study intervention.
- •Participants must use a condom from signing ICF, during study intervention, and for 6 months after the last dose of study drug, with all sexual partners.
排除标准
- •Participants with a history of MDS/AML or with features suggestive of MDS/AML (as determined by prior diagnostic investigation). In case there is no clinical MDS/AML suspicion, no specific screening for MDS/AML (by BM/bone biopsy) is required.
- •Participants with any known predisposition to bleeding.
- •Any history of persisting (> 2 weeks) severe cytopenia.
- •Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of AZD5305 and/or the assigned NHA.
- •History of another primary malignancy, with exceptions.
- •Persistent toxicities (CTCAE Grade ≥ 2) caused by previous anticancer therapy.
- •Spinal cord compression or brain metastases unless asymptomatic, stable, and not requiring steroids for at least 4 weeks prior to start of study intervention.
- •Cardiac criteria, including history of arrhythmia and cardiovascular disease.
- •Any prior anticancer pharmacotherapy or surgery for metastatic prostate cancer, with exceptions.
- •Prior treatment within 14 days with blood product support or growth factor support.
- •Participants who are unevaluable for both bone and soft tissue progression.
研究组 & 干预措施
Arm 1: Saruparib (AZD5305) + Physician's Choice NHA
Saruparib (AZD5305) + physician's choice NHA (Abiraterone, Darolutamide, or Enzalutamide)
干预措施: Enzalutamide (Drug)
Arm 1: Saruparib (AZD5305) + Physician's Choice NHA
Saruparib (AZD5305) + physician's choice NHA (Abiraterone, Darolutamide, or Enzalutamide)
干预措施: Darolutamide (Drug)
Arm 1: Saruparib (AZD5305) + Physician's Choice NHA
Saruparib (AZD5305) + physician's choice NHA (Abiraterone, Darolutamide, or Enzalutamide)
干预措施: Saruparib (Drug)
Arm 1: Saruparib (AZD5305) + Physician's Choice NHA
Saruparib (AZD5305) + physician's choice NHA (Abiraterone, Darolutamide, or Enzalutamide)
干预措施: Abiraterone Acetate (Drug)
Arm 2: Placebo + Physician's Choice NHA
Placebo + physician's choice NHA (Abiraterone, Darolutamide, or Enzalutamide)
干预措施: Abiraterone Acetate (Drug)
Arm 2: Placebo + Physician's Choice NHA
Placebo + physician's choice NHA (Abiraterone, Darolutamide, or Enzalutamide)
干预措施: Darolutamide (Drug)
Arm 2: Placebo + Physician's Choice NHA
Placebo + physician's choice NHA (Abiraterone, Darolutamide, or Enzalutamide)
干预措施: Enzalutamide (Drug)
Arm 2: Placebo + Physician's Choice NHA
Placebo + physician's choice NHA (Abiraterone, Darolutamide, or Enzalutamide)
干预措施: Placebo (Drug)
结局指标
主要结局
Radiographic Progression-Free Survival (rPFS)
时间窗: up to approximately 50 months
rPFS is defined as the time from randomisation to radiographic progression, as assessed by the investigator per RECIST 1.1 (soft tissue) and/or PCWG3 criteria (bone), or, death due to any cause.
次要结局
- Overall Survival (OS)(up to approximately 90 months)
- Second Progression-Free Survival (PFS2)(up to approximately 50 months)
- Time to First Subsequent Therapy or Death (TFST)(up to approximately 50 months)
- Symptomatic Skeletal Event-Free Survival (SSE-FS)(up to approximately 50 months)
- Time to the First Castration-Resistant Event (TTCR)(up to approximately 50 months)
- Time to Pain Progression (TTPP)(up to approximately 50 months)
- Time To Deterioration in Urinary Symptoms (TTDUS)(up to approximately 50 months)
- Time to Deterioration in Fatigue (TTDF)(up to approximately 50 months)
- Time to Deterioration in Physical Function (TTDPF)(up to approximately 50 months)
- Health-related Quality of Life (HrQoL)(up to approximately 50 months)
- BRCA and other HRR gene mutation status.(at screening)
- Plasma concentrations of AZD5305(up to approximately 10 months)
- Samples will be used to develop complementary or companion diagnostics by analyzing their performance characteristics and calculate their consistency with clinical trial assays used for enrolment onto the study.(up to approximately 50 months)
- Assessment of PSA (prostate-specific antigen) in participants in mCSPC(up to approximately 50 months)