Darolutamide + Consolidation Radiotherapy in Advanced Prostate Cancer Detected by PSMA
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 65
- 试验地点
- 16
- 主要终点
- Undetectable PSA at 12 months
研究概览
简要总结
Darolutamide is a drug that has a proven survival benefit in non-metastatic (M0) castrate resistant prostate cancer when using conventional imaging. However, it is estimated that >90% of patients have disease apparent when using PSMA PET. This study investigates the use of local consolidation radiotherapy in this cohort of men.
详细描述
This study explores the use of local consolidation therapy in the setting of Darolutamide in the initial diagnosis of metastatic castrate resistant prostate cancer (mCRPC). In the chemotherapy naïve mCRPC setting, the pattern of disease is of limited volume metastases (1-5) in 34%-40% of cases. As progression at known sites of macroscopic disease is the predominant cause of failure on systemic therapies, local consolidation therapy with stereotactic ablative body radiotherapy (SABR) may improve progression free survival (PFS) and overall survival (OS). This approach has been tested in the setting of lung cancer, in which consolidation SABR has resulted in OS benefit (HR of 0.40) in phase II studies. The novel approach of local consolidation therapy has not been tested as yet in mCRPC.
The secondary objective of this study proposal is to better understand the pattern of disease distribution at first diagnosis of CRPC. Previous studies have used conventional bone scan and CT imaging, and with these investigations the proportion of patients that are 'M0' is ~35%1. However, in the new era of PSMA PET, which is far more sensitive than conventional imaging, there exists a new group of men who are M0 on conventional imaging but are M1 on PSMA PET staging.
Thus, in the DECREASE study population, we expect the vast majority of patients with conventionally imaged 'M0 CRPC' will have disease detectable on PSMA PET scanning. In this context, the central hypothesis of this trial is that the addition of consolidation radiotherapy to darolutamide to PSMA detected sites of disease will improve the clinical outcome of patients compared to those patients receiving darolutamide 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
- •≥ 18 years of age and provided written Informed Consent
- •Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features
- •Castration-resistant prostate cancer, defined as at least 2 consecutive PSA rises obtained at least 1 week apart in the setting of castrate testosterone levels
- •Castrate level of serum testosterone (<1.7 nmol/l [50 ng/dl]) on gonadotrophin - releasing hormone (GnRH) agonist or antagonist therapy or after bilateral orchiectomy
- •A baseline PSA level of at least 1ng per millilitre and a PSA doubling time of 10 months or less
- •Adequate bone marrow reserve and organ function Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •At least 1 site of PSMA-avid disease on PSMA-PET/CT imaging in any of the following regions; At least 1 site of PSMA-avid disease on PSMA-PET/CT imaging in any of the following regions:
- •Local recurrence within the prostate gland or prostate bed
- •Regional lymph node disease (below the aortic bifurcation)
- •Extra-pelvic lymph node, bone or soft tissue metastatic disease
排除标准
- •Patients with detectable metastases or a history of metastatic disease on conventional imaging
- •Prior treatment with second-generation androgen receptor (AR) antagonists, CYP17 enzyme inhibitors or oral ketoconazole
- •Use of oestrogens or 5-α reductase inhibitors or anti-androgens within 28 days before randomisation
- •Use of systemic corticosteroid with a dose greater than the equivalent 10 mg of prednisone/day within 28 days before randomisation
- •Radiotherapy within 12 weeks prior to randomisation
- •Initiation of treatment with an osteoclast-targeted therapy to prevent skeletal-related events within 12 weeks before randomisation
- •Any of the following within 6 months before randomisation: stroke, myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft; congestive heart failure New York Heart Association (NYHA) Class III or IV
- •Uncontrolled hypertension
- •Prior malignancy
- •Gastrointestinal disorder or procedure that expects to interfere significantly with the absorption of study treatment
- •Unable to swallow study medications and comply with study requirements
研究组 & 干预措施
Darolutamide
Darolutimide 600mg BD
干预措施: Darolutamide (Drug)
Local consolidation Radiotherapy + Darolutamide
Darolutimide 600mg BD + local consolidative radiotherapy, with a biological equivalent dose of 30Gy/10fx or greater if delivered with SABR. SABR is the preferred treatment approach, however conventional radiotherapy is acceptable. To up to 5 sites of disease
干预措施: Darolutamide (Drug)
Local consolidation Radiotherapy + Darolutamide
Darolutimide 600mg BD + local consolidative radiotherapy, with a biological equivalent dose of 30Gy/10fx or greater if delivered with SABR. SABR is the preferred treatment approach, however conventional radiotherapy is acceptable. To up to 5 sites of disease
干预措施: Radiotherapy (Radiation)
结局指标
主要结局
Undetectable PSA at 12 months
时间窗: 12 months
Undetectable PSA at 12 months
次要结局
- Radiological progression free survival(36 months)
- Treatment related adverse event(36 months)
- Biochemical progression free survival(36 months)
- Patterns of disease on PSMA PET/CT after 12 weeks of commencing Darolutamide, and at time of disease progression(3 months)
- Distribution of disease on baseline PSMA-PET/CT imaging(36 months)
- Overall survival(36 months)