A Randomized Trial of Neoadjuvant Leuprorelin, Darolutamide or Both Prior to Radical Prostatectomy for Intermediate or High-risk Prostate Cancer
试验速览
- 阶段
- 4 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 144
- 试验地点
- 6
- 主要终点
- Proportion of patients with minimal residual disease
研究概览
简要总结
A Randomized Trial of Neoadjuvant Leuprorelin, Darolutamide or Both Prior to Radical Prostatectomy for Intermediate or High-risk Prostate Cancer. Prospective, randomized, parallel group, open-label with blinded endpoint adjudication multicenter clinical trial.To assess, among patients with unfavorable intermediate to high-risk prostate cancer, whether a neoadjuvant combined treatment with leuprorelin (Leuprorelin) and darolutamide is superior to monotherapy in terms of complete or almost complete pathological response.A total of 144 patients with unfavorable intermediate to high-risk prostate cancer scheduled for radical prostatectomy with extended pelvic lymph node dissection will be randomized 1:1:1 to oral darolutamide, SC leuprorelin (Leuprorelin) or both (48 patients per arm) for 24 weeks.
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
- Single (Outcomes Assessor)
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
- •Men ≥18 years of age;
- •Histologically confirmed unfavorable intermediate or high/very high risk non metastatic (by conventional imaging) prostate adenocarcinoma intended for surgery without neuroendocrine differentiation or small cell features;
- •Unfavorable intermediate-risk:
- •ISUP grade 3, and/or > 50% positive biopsy cores and/or at least two intermediate-risk factors. Intermediate-risk factors:
- •Clinical tumor stage T2b or T2c (MRI based);
- •ISUP grade 2 or 3;
- •Prostate-specific antigen (PSA) level of 10-20 ng/mL.
- •High-risk or very high-risk:
- •≥cT3a (MRI based) or ISUP 4-5 or PSA>20 ng/mL;
- •ECOG 0-1;
- •Baseline testosterone > 230 ng/dL;
- •No prior prostate cancer treatment;
- •Sexually active male subjects must agree to use condoms as an effective barrier method and refrain from sperm donation, and/or their female partners of reproductive potential to use a method of effective birth control, during the treatment with darolutamide and for 1 week after the end of treatment with darolutamide to prevent pregnancy;
- •Written informed consent.
排除标准
- •Unresectable prostate cancer;
- •Histology of small cell carcinoma prostate cancer or adenocarcinoma with neuroendocrine features;
- •Any prior prostate cancer treatment;
- •Any active infection requiring IV antibiotics;
- •Known additional malignancy that has a life-expectancy < 2 years;
- •Had any of the following within 6 months before randomization: stroke, myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, heart failure with New York Heart Association Class Functional III or IV;
- •Uncontrolled severe hypertension as indicated by a resting systolic BP ≥ 180 mmHg or diastolic BP ≥ 110 mmHg despite medical management;
- •A gastrointestinal (GI) disorder or procedure which is expected to interfere significantly with absorption of darolutamide;
- •Inability to swallow oral medications;
- •Receipt of medications (e.g. finasteride, dutasteride) or agents that are likely to alter serum PSA levels within <= 42 days or 5 half-lives prior to registration, whichever is shorter.
研究组 & 干预措施
Darolutamide + ADT leuprorelin
干预措施: Darolutamide Oral Tablet (Drug)
Darolutamide + ADT leuprorelin
干预措施: leuprorelin (Drug)
Darolutamide
干预措施: Darolutamide Oral Tablet (Drug)
Leuprorelin
干预措施: leuprorelin (Drug)
结局指标
主要结局
Proportion of patients with minimal residual disease
时间窗: Patients are expected to undergo surgery after no more than 30 days after completion of the neoadjuvant regimen therapy, which will last for 24 weeks after randomization in all 3 groups.
Proportion of patients with minimal residual disease, defined as residual cancer burden (RCB) ≤ 0.25 cm3 (tumor volume ≤ 0.5 cm3 × tumor cellularity ≤ 50%) or complete pathological response, assessed by pathology of surgical specimen obtained from prostatectomy.
次要结局
- Complete biochemical response assessed by serum PSA with the rate of PSA<0,2 ng/dL(24 weeks)
- Treatment emergent adverse events and serious adverse events.(24 weeks)
- PSA levels at 3 months after prostatectomy.(in 42 weeks)
- Testosterone levels.(in 42 weeks)
- Number of positive lymph nodes.(30 weeks)
- Number of positive surgical margins.(30 weeks)
- Perioperative complications.(42 weeks)
- Quality of life using IEEF5 and HRQoL questionnaires pre and post neoadjuvant treatment.(42 weeks)
- Downstaging (changes in TNM - Classification of Malignant Tumours stage) based on surgical specimen.(30 weeks)